Sample records for abnormal basal ganglia

  1. Basal Ganglia Shape Abnormalities in the Unaffected Siblings of Schizophrenia Patients

    PubMed Central

    Mamah, Daniel; Harms, Michael P.; Wang, Lei; Barch, Deanna; Thompson, Paul; Kim, Jaeyun; Miller, Michael I.; Csernansky, John G.

    2008-01-01

    Objective Abnormalities of basal ganglia structure in schizophrenia have been attributed to the effects of antipsychotic drugs. Our aim was to test the hypothesis that abnormalities of basal ganglia structure are intrinsic features of schizophrenia, by assessing basal ganglia volume and shape in the unaffected siblings of schizophrenia subjects. Method The study involved 25 pairs of schizophrenia subjects and their unaffected siblings and 40 pairs of healthy controls and their siblings. Large deformation, high-dimensional brain mapping was used to obtain surface representations of the caudate, putamen, and globus pallidus. Surfaces were derived from transformations of anatomical templates and shapes were analyzed using reduced-dimensional measures of surface variability (i.e. principal components and canonical analysis). Canonical functions were derived using schizophrenia and control groups, and were then used to compare shapes in the sibling groups. To visualize shape differences, maps of the estimated surface displacement between groups were created. Results In the caudate, putamen and globus pallidus, the degree of shape abnormality observed in the siblings of the schizophrenia subjects was intermediate between the schizophrenia subjects and the controls. In the schizophrenia subjects, significant correlations were observed between measures of caudate, putamen and globus pallidus structure and the selected measures of lifetime psychopathology. Conclusions Attenuated abnormalities of basal ganglia structure are present in the unaffected siblings of schizophrenia subjects. This finding implies that basal ganglia structural abnormalities observed in subjects with schizophrenia are at least in part an intrinsic feature of the illness. PMID:18295189

  2. Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia.

    PubMed

    Kita, Hitoshi; Kita, Takako

    2011-07-13

    The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

  3. Sonographic detection of basal ganglia abnormalities in spasmodic dysphonia.

    PubMed

    Walter, U; Blitzer, A; Benecke, R; Grossmann, A; Dressler, D

    2014-02-01

    Abnormalities of the lenticular nucleus (LN) on transcranial sonography (TCS) are a characteristic finding in idiopathic segmental and generalized dystonia. Our intention was to study whether TCS detects basal ganglia abnormalities also in spasmodic dysphonia, an extremely focal form of dystonia. Transcranial sonography of basal ganglia, substantia nigra and ventricles was performed in 14 patients with spasmodic dysphonia (10 women, four men; disease duration 16.5 ± 6.1 years) and 14 age- and sex-matched healthy controls in an investigator-blinded setting. Lenticular nucleus hyperechogenicity was found in 12 spasmodic dysphonia patients but only in one healthy individual (Fisher's exact test, P < 0.001) whilst other TCS findings did not differ. The area of LN hyperechogenic lesions quantified on digitized image analysis correlated with spasmodic dysphonia severity (Spearman test, r = 0.82, P < 0.001). Our findings link the underlying pathology of spasmodic dysphonia to that of more widespread forms of dystonia. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

  4. The expanding universe of disorders of the basal ganglia.

    PubMed

    Obeso, Jose A; Rodriguez-Oroz, Maria C; Stamelou, Maria; Bhatia, Kailash P; Burn, David J

    2014-08-09

    The basal ganglia were originally thought to be associated purely with motor control. However, dysfunction and pathology of different regions and circuits are now known to give rise to many clinical manifestations beyond the association of basal ganglia dysfunction with movement disorders. Moreover, disorders that were thought to be caused by dysfunction of the basal ganglia only, such as Parkinson's disease and Huntington's disease, have diverse abnormalities distributed not only in the brain but also in the peripheral and autonomic nervous systems; this knowledge poses new questions and challenges. We discuss advances and the unanswered questions, and ways in which progress might be made. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. The Basal Ganglia-Circa 1982

    NASA Technical Reports Server (NTRS)

    Mehler, William R.

    1981-01-01

    Our review has shown that recent studies with the new anterograde and retrograde axon transport methods have confirmed and extended our knowledge of the projection of the basal ganglia and clarified their sites of origin. They have thrown new light on certain topographic connectional relationships and revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Similarly, attention has been drawn to the fact that there have also been many new histochemical techniques introduced in recent years that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in, or interconnecting with, the basal ganglia. However, although these new morphological biochemical maps are very complex and technically highly advanced, our understanding of the function controlled by the basal ganglia still remains primitive. The reader who is interested in some new ideas of the functional aspects of the basal ganglia is directed to Nauta's proposed conceptual reorganization of the basal ganglia telencephalon and to Marsden's more clinically orientated appraisal of the unsolved mysteries of the basal ganglia participation in the control of movement.

  6. Imaging basal ganglia function

    PubMed Central

    BROOKS, DAVID J.

    2000-01-01

    In this review, the value of functional imaging for providing insight into the role of the basal ganglia in motor control is reviewed. Brain activation findings in normal subjects and Parkinson's disease patients are examined and evidence supporting the existence for functionally independent distributed basal ganglia-frontal loops is presented. It is argued that the basal ganglia probably act to focus and filter cortical output, optimising the running of motor programs. PMID:10923986

  7. Functional neuroanatomy of the basal ganglia.

    PubMed

    Lanciego, José L; Luquin, Natasha; Obeso, José A

    2012-12-01

    The "basal ganglia" refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amplified with the emergence of new data. Furthermore, parallel circuits subserve the other functions of the basal ganglia engaging associative and limbic territories. Disruption of the basal ganglia network forms the basis for several movement disorders. This article provides a comprehensive account of basal ganglia functional anatomy and chemistry and the major pathophysiological changes underlying disorders of movement. We try to answer three key questions related to the basal ganglia, as follows: What are the basal ganglia? What are they made of? How do they work? Some insight on the canonical basal ganglia model is provided, together with a selection of paradoxes and some views over the horizon in the field.

  8. [Anti-basal ganglia antibody].

    PubMed

    Hayashi, Masaharu

    2013-04-01

    Sydenham's chorea (SC) is a major manifestation of rheumatic fever, and the production of anti-basal ganglia antibodies (ABGA) has been proposed in SC. The pathogenesis is hypothesized as autoimmune targeting of the basal ganglia via molecular mimicry, triggered by streptococcal infection. The spectrum of diseases in which ABGA may be involved has been broadened to include other extrapyramidal movement disorders, such as tics, dystonia, and Parkinsonism, as well as other psychiatric disorders. The autoimmune hypothesis in the presence and absence of ABGA has been suggested in Tourette's syndrome (TS), early onset obsessive-compulsive disorders (OCD), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Recently, the relationship between ABGA and dopamine neurons in the basal ganglia has been examined, and autoantibodies against dopamine receptors were detected in the sera from patients with basal ganglia encephalitis. In Japan, the occurrence of subacute encephalitis, where patients suffer from episodes of altered behavior and involuntary movements, has increased. Immune-modulating treatments are effective, indicating the involvement of an autoimmune mechanism. We aimed to detect the anti-neuronal autoantibodies in such encephalitis, using immunohistochemical assessment of patient sera. The sera from patients showing involuntary movements had immunoreactivity for basal ganglia neurons. Further epitopes for ABGA will be investigated in basal ganglia disorders other than SC, TS, OCD, and PANDAS.

  9. Bicycling suppresses abnormal beta synchrony in the Parkinsonian basal ganglia.

    PubMed

    Storzer, Lena; Butz, Markus; Hirschmann, Jan; Abbasi, Omid; Gratkowski, Maciej; Saupe, Dietmar; Vesper, Jan; Dalal, Sarang S; Schnitzler, Alfons

    2017-10-01

    Freezing of gait is a poorly understood symptom of Parkinson disease, and can severely disrupt the locomotion of affected patients. However, bicycling ability remains surprisingly unaffected in most patients suffering from freezing, suggesting functional differences in the motor network. The purpose of this study was to characterize and contrast the oscillatory dynamics underlying bicycling and walking in the basal ganglia. We present the first local field potential recordings directly comparing bicycling and walking in Parkinson disease patients with electrodes implanted in the subthalamic nuclei for deep brain stimulation. Low (13-22Hz) and high (23-35Hz) beta power changes were analyzed in 22 subthalamic nuclei from 13 Parkinson disease patients (57.5 ± 5.9 years old, 4 female). The study group consisted of 5 patients with and 8 patients without freezing of gait. In patients without freezing of gait, both bicycling and walking led to a suppression of subthalamic beta power (13-35Hz), and this suppression was stronger for bicycling. Freezers showed a similar pattern in general. Superimposed on this pattern, however, we observed a movement-induced, narrowband power increase around 18Hz, which was evident even in the absence of freezing. These results indicate that bicycling facilitates overall suppression of beta power. Furthermore, movement leads to exaggerated synchronization in the low beta band specifically within the basal ganglia of patients susceptible to freezing. Abnormal ∼18Hz oscillations are implicated in the pathophysiology of freezing of gait, and suppressing them may form a key strategy in developing potential therapies. Ann Neurol 2017;82:592-601. © 2017 American Neurological Association.

  10. Motor functions of the basal ganglia.

    PubMed

    Phillips, J G; Bradshaw, J L; Iansek, R; Chiu, E

    1993-01-01

    A study of movement disorders such as Parkinson's disease and Huntington's disease can provide an indication of the motor functions of the basal ganglia. Basal-ganglia diseases affect voluntary movement and can cause involuntary movement. Deficits are often manifested during the coordination of fine multi-joint movements (e.g., handwriting). The disturbances of motor control (e.g. akinesia, bradykinesia) caused by basal-ganglia disorders are illustrated. Data suggest that the basal ganglia play an important role in the automatic execution of serially ordered complex movements.

  11. Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition.

    PubMed

    McCairn, Kevin W; Iriki, Atsushi; Isoda, Masaki

    2013-01-09

    Motor tics, a cardinal symptom of Tourette syndrome (TS), are hypothesized to arise from abnormalities within cerebro-basal ganglia circuits. Yet noninvasive neuroimaging of TS has previously identified robust activation in the cerebellum. To date, electrophysiological properties of cerebellar activation and its role in basal ganglia-mediated tic expression remain unknown. We performed multisite, multielectrode recordings of single-unit activity and local field potentials from the cerebellum, basal ganglia, and primary motor cortex using a pharmacologic monkey model of motor tics/TS. Following microinjections of bicuculline into the sensorimotor putamen, periodic tics occurred predominantly in the orofacial region, and a sizable number of cerebellar neurons showed phasic changes in activity associated with tic episodes. Specifically, 64% of the recorded cerebellar cortex neurons exhibited increases in activity, and 85% of the dentate nucleus neurons displayed excitatory, inhibitory, or multiphasic responses. Critically, abnormal discharges of cerebellar cortex neurons and excitatory-type dentate neurons mostly preceded behavioral tic onset, indicating their central origins. Latencies of pathological activity in the cerebellum and primary motor cortex substantially overlapped, suggesting that aberrant signals may be traveling along divergent pathways to these structures from the basal ganglia. Furthermore, the occurrence of tic movement was most closely associated with local field potential spikes in the cerebellum and primary motor cortex, implying that these structures may function as a gate to release overt tic movements. These findings indicate that tic-generating networks in basal ganglia mediated tic disorders extend beyond classical cerebro-basal ganglia circuits, leading to global network dysrhythmia including cerebellar circuits.

  12. Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome

    PubMed Central

    Portmann, Thomas; Ellegood, Jacob; Dolen, Gul; Bader, Patrick L.; Grueter, Brad A.; Goold, Carleton; Fisher, Elaine; Clifford, Katherine; Rengarajan, Pavitra; Kalikhman, David; Loureiro, Darren; Saw, Nay L.; Zhengqui, Zhou; Miller, Michael A.; Lerch, Jason P.; Henkelman, Mark; Shamloo, Mehrdad; Malenka, Robert C.; Crawley, Jacqueline N.; Dolmetsch, Ricardo E.

    2014-01-01

    Summary A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11+/−). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2+) and fewer dopamine-sensitive (Drd1+) neurons in deep layers of cortex. Electrophysiological recordings of Drd2+ MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11+/− mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11+/− mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism. PMID:24794428

  13. Basal Ganglia Circuits as Targets for Neuromodulation in Parkinson Disease.

    PubMed

    DeLong, Mahlon R; Wichmann, Thomas

    2015-11-01

    The revival of stereotactic surgery for Parkinson disease (PD) in the 1990s, with pallidotomy and then with high-frequency deep brain stimulation (DBS), has led to a renaissance in functional surgery for movement and other neuropsychiatric disorders. To examine the scientific foundations and rationale for the use of ablation and DBS for treatment of neurologic and psychiatric diseases, using PD as the primary example. A summary of the large body of relevant literature is presented on anatomy, physiology, pathophysiology, and functional surgery for PD and other basal ganglia disorders. The signs and symptoms of movement disorders appear to result largely from signature abnormalities in one of several parallel and largely segregated basal ganglia thalamocortical circuits (ie, the motor circuit). The available evidence suggests that the varied movement disorders resulting from dysfunction of this circuit result from propagated disruption of downstream network activity in the thalamus, cortex, and brainstem. Ablation and DBS act to free downstream networks to function more normally. The basal ganglia thalamocortical circuit may play a key role in the expression of disordered movement, and the basal ganglia-brainstem projections may play roles in akinesia and disturbances of gait. Efforts are under way to target circuit dysfunction in brain areas outside of the traditionally implicated basal ganglia thalamocortical system, in particular, the pedunculopontine nucleus, to address gait disorders that respond poorly to levodopa and conventional DBS targets. Deep brain stimulation is now the treatment of choice for many patients with advanced PD and other movement disorders. The success of DBS and other forms of neuromodulation for neuropsychiatric disorders is the result of the ability to modulate circuit activity in discrete functional domains within the basal ganglia circuitry with highly focused interventions, which spare uninvolved areas that are often disrupted with

  14. The connectome of the basal ganglia.

    PubMed

    Schmitt, Oliver; Eipert, Peter; Kettlitz, Richard; Leßmann, Felix; Wree, Andreas

    2016-03-01

    The basal ganglia of the laboratory rat consist of a few core regions that are specifically interconnected by efferents and afferents of the central nervous system. In nearly 800 reports of tract-tracing investigations the connectivity of the basal ganglia is documented. The readout of connectivity data and the collation of all the connections of these reports in a database allows to generate a connectome. The collation, curation and analysis of such a huge amount of connectivity data is a great challenge and has not been performed before (Bohland et al. PloS One 4:e7200, 2009) in large connectomics projects based on meta-analysis of tract-tracing studies. Here, the basal ganglia connectome of the rat has been generated and analyzed using the consistent cross-platform and generic framework neuroVIISAS. Several advances of this connectome meta-study have been made: the collation of laterality data, the network-analysis of connectivity strengths and the assignment of regions to a hierarchically organized terminology. The basal ganglia connectome offers differences in contralateral connectivity of motoric regions in contrast to other regions. A modularity analysis of the weighted and directed connectome produced a specific grouping of regions. This result indicates a correlation of structural and functional subsystems. As a new finding, significant reciprocal connections of specific network motifs in this connectome were detected. All three principal basal ganglia pathways (direct, indirect, hyperdirect) could be determined in the connectome. By identifying these pathways it was found that there exist many further equivalent pathways possessing the same length and mean connectivity weight as the principal pathways. Based on the connectome data it is unknown why an excitation pattern may prefer principal rather than other equivalent pathways. In addition to these new findings the local graph-theoretical features of regions of the connectome have been determined. By

  15. Metabolite alterations in basal ganglia associated with methamphetamine-related psychiatric symptoms. A proton MRS study.

    PubMed

    Sekine, Yoshimoto; Minabe, Yoshio; Kawai, Masayoshi; Suzuki, Katsuaki; Iyo, Masaomi; Isoda, Haruo; Sakahara, Harumi; Ashby, Charles R; Takei, Nori; Mori, Norio

    2002-09-01

    Following the chronic use of methamphetamine, some individuals experience psychosis and anxiety. One reason may be the persistence of metabolite abnormalities in the brain of currently abstinent former methamphetamine users. In this study, N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr+PCr), and choline-containing compound (Cho) levels were measured in the left and right basal ganglia using proton magnetic resonance spectroscopy (MRS) in 13 abstinent methamphetamine users and 11 healthy comparison subjects with no history of illicit drug use. The methamphetamine users showed a significantly reduced Cr+PCr/Cho ratio in the bilateral basal ganglia compared with the healthy comparison subjects. Furthermore, the reduction in the Cr+PCr/Cho ratio was significantly correlated with the duration of methamphetamine use and with the severity of residual psychiatric symptoms. NAA/Cho ratios in the bilateral basal ganglia did not significantly differ between methamphetamine users and comparison subjects. These findings suggest that protracted use of methamphetamine may cause metabolite alterations in the basal ganglia. Furthermore, residual psychiatric symptoms may be attributable to the metabolite alterations in the basal ganglia.

  16. Abnormal brain MRI signals in the splenium of the corpus callosum, basal ganglia and internal capsule in a suspected case with tuberculous meningitis.

    PubMed

    Hirotani, Makoto; Yabe, Ichiro; Hamada, Shinsuke; Tsuji, Sachiko; Kikuchi, Seiji; Sasaki, Hidenao

    2007-01-01

    A 34-year-old man visited the hospital with chief complaints of headache, fever, and disturbance of consciousness. In view of his clinical condition, the course of the disease, and results of examination, he was diagnosed with viral meningitis and treated accordingly. However, his clinical condition worsened, and MRI revealed abnormal signals in the splenium of the corpus callosum, in the basal ganglia and in the internal capsule, as well as the presence of severe inflammation in the base of the brain. Since he had a high ADA level in the cerebrospinal fluid and was consequently suspected to have tuberculous meningitis, he was placed on antitubercular agents. Then, his clinical condition began to improve. Additional steroid pulse therapy further improved his condition, and abnormal signals in the splenium of the corpus callosum and the basal ganglia resolved. This valuable case suggests that an immune mechanism contributed to the occurrence of central nervous system symptoms associated with tuberculous meningitis.

  17. Learning and memory functions of the Basal Ganglia.

    PubMed

    Packard, Mark G; Knowlton, Barbara J

    2002-01-01

    Although the mammalian basal ganglia have long been implicated in motor behavior, it is generally recognized that the behavioral functions of this subcortical group of structures are not exclusively motoric in nature. Extensive evidence now indicates a role for the basal ganglia, in particular the dorsal striatum, in learning and memory. One prominent hypothesis is that this brain region mediates a form of learning in which stimulus-response (S-R) associations or habits are incrementally acquired. Support for this hypothesis is provided by numerous neurobehavioral studies in different mammalian species, including rats, monkeys, and humans. In rats and monkeys, localized brain lesion and pharmacological approaches have been used to examine the role of the basal ganglia in S-R learning. In humans, study of patients with neurodegenerative diseases that compromise the basal ganglia, as well as research using brain neuroimaging techniques, also provide evidence of a role for the basal ganglia in habit learning. Several of these studies have dissociated the role of the basal ganglia in S-R learning from those of a cognitive or declarative medial temporal lobe memory system that includes the hippocampus as a primary component. Evidence suggests that during learning, basal ganglia and medial temporal lobe memory systems are activated simultaneously and that in some learning situations competitive interference exists between these two systems.

  18. Striatal dysfunction increases basal ganglia output during motor cortex activation in parkinsonian rats.

    PubMed

    Belluscio, Mariano A; Riquelme, Luis A; Murer, M Gustavo

    2007-05-01

    During movement, inhibitory neurons in the basal ganglia output nuclei show complex modulations of firing, which are presumptively driven by corticostriatal and corticosubthalamic input. Reductions in discharge should facilitate movement by disinhibiting thalamic and brain stem nuclei while increases would do the opposite. A proposal that nigrostriatal dopamine pathway degeneration disrupts trans-striatal pathways' balance resulting in sustained overactivity of basal ganglia output nuclei neurons and Parkinson's disease clinical signs is not fully supported by experimental evidence, which instead shows abnormal synchronous oscillatory activity in animal models and patients. Yet, the possibility that variation in motor cortex activity drives transient overactivity in output nuclei neurons in parkinsonism has not been explored. In Sprague-Dawley rats with 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions, approximately 50% substantia nigra pars reticulata (SNpr) units show abnormal cortically driven slow oscillations of discharge. Moreover, these units selectively show abnormal responses to motor cortex stimulation consisting in augmented excitations of an odd latency, which overlapped that of inhibitory responses presumptively mediated by the trans-striatal direct pathway in control rats. Delivering D1 or D2 dopamine agonists into the striatum of parkinsonian rats by reverse microdialysis reduced these abnormal excitations but had no effect on pathological oscillations. The present study establishes that dopamine-deficiency related changes of striatal function contribute to producing abnormally augmented excitatory responses to motor cortex stimulation in the SNpr. If a similar transient overactivity of basal ganglia output were driven by motor cortex input during movement, it could contribute to impeding movement initiation or execution in Parkinson's disease.

  19. Anomalous basal ganglia connectivity and obsessive–compulsive behaviour in patients with Prader Willi syndrome

    PubMed Central

    Pujol, Jesus; Blanco-Hinojo, Laura; Esteba-Castillo, Susanna; Caixàs, Assumpta; Harrison, Ben J.; Bueno, Marta; Deus, Joan; Rigla, Mercedes; Macià, Dídac; Llorente-Onaindia, Jone; Novell-Alsina, Ramón

    2016-01-01

    Background Prader Willi syndrome is a genetic disorder with a behavioural expression characterized by the presence of obsessive–compulsive phenomena ranging from elaborate obsessive eating behaviour to repetitive skin picking. Obsessive–compulsive disorder (OCD) has been recently associated with abnormal functional coupling between the frontal cortex and basal ganglia. We have tested the potential association of functional connectivity anomalies in basal ganglia circuits with obsessive–compulsive behaviour in patients with Prader Willi syndrome. Methods We analyzed resting-state functional MRI in adult patients and healthy controls. Whole-brain functional connectivity maps were generated for the dorsal and ventral aspects of the caudate nucleus and putamen. A selected obsessive–compulsive behaviour assessment included typical OCD compulsions, self picking and obsessive eating behaviour. Results We included 24 adults with Prader Willi syndrome and 29 controls in our study. Patients with Prader Willi syndrome showed abnormal functional connectivity between the prefrontal cortex and basal ganglia and within subcortical structures that correlated with the presence and severity of obsessive–compulsive behaviours. In addition, abnormally heightened functional connectivity was identified in the primary sensorimotor cortex–putamen loop, which was strongly associated with self picking. Finally, obsessive eating behaviour correlated with abnormal functional connectivity both within the basal ganglia loops and between the striatum and the hypothalamus and the amygdala. Limitations Limitations of the study include the difficulty in evaluating the nature of content of obsessions in patients with Prader Willi Syndrome and the risk of excessive head motion artifact on brain imaging. Conclusion Patients with Prader Willi syndrome showed broad functional connectivity anomalies combining prefrontal loop alterations characteristic of OCD with 1) enhanced coupling in the

  20. Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

    PubMed

    Wichmann, Thomas; DeLong, Mahlon R

    2016-04-01

    Deep brain stimulation (DBS) is highly effective for both hypo- and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal ganglia-thalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

  1. Changes in basal ganglia processing of cortical input following magnetic stimulation in Parkinsonism.

    PubMed

    Tischler, Hadass; Moran, Anan; Belelovsky, Katya; Bronfeld, Maya; Korngreen, Alon; Bar-Gad, Izhar

    2012-12-01

    Parkinsonism is associated with major changes in neuronal activity throughout the cortico-basal ganglia loop. Current measures quantify changes in baseline neuronal and network activity but do not capture alterations in information propagation throughout the system. Here, we applied a novel non-invasive magnetic stimulation approach using a custom-made mini-coil that enabled us to study transmission of neuronal activity throughout the cortico-basal ganglia loop in both normal and parkinsonian primates. By magnetically perturbing cortical activity while simultaneously recording neuronal responses along the cortico-basal ganglia loop, we were able to directly investigate modifications in descending cortical activity transmission. We found that in both the normal and parkinsonian states, cortical neurons displayed similar multi-phase firing rate modulations in response to magnetic stimulation. However, in the basal ganglia, large synaptically driven stereotypic neuronal modulation was present in the parkinsonian state that was mostly absent in the normal state. The stimulation-induced neuronal activity pattern highlights the change in information propagation along the cortico-basal ganglia loop. Our findings thus point to the role of abnormal dynamic activity transmission rather than changes in baseline activity as a major component in parkinsonian pathophysiology. Moreover, our results hint that the application of transcranial magnetic stimulation (TMS) in human patients of different disorders may result in different neuronal effects than the one induced in normal subjects. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Basal Ganglia Calcification with Tetanic Seizure Suggest Mitochondrial Disorder.

    PubMed

    Finsterer, Josef; Enzelsberger, Barbara; Bastowansky, Adam

    2017-04-09

    BACKGROUND Basal ganglia calcification (BGC) is a rare sporadic or hereditary central nervous system (CNS) abnormality, characterized by symmetric or asymmetric calcification of the basal ganglia. CASE REPORT We report the case of a 65-year-old Gypsy female who was admitted for a tetanic seizure, and who had a history of polyneuropathy, restless-leg syndrome, retinopathy, diabetes, hyperlipidemia, osteoporosis with consecutive hyperkyphosis, cervicalgia, lumbalgia, struma nodosa requiring thyroidectomy and consecutive hypothyroidism, adipositas, resection of a vocal chord polyp, arterial hypertension, coronary heart disease, atheromatosis of the aorta, peripheral artery disease, chronic obstructive pulmonary disease, steatosis hepatis, mild renal insufficiency, long-term hypocalcemia, hyperphosphatemia, impingement syndrome, spondylarthrosis of the lumbar spine, and hysterectomy. History and clinical presentation suggested a mitochondrial defect which also manifested as hypoparathyroidism or Fanconi syndrome resulting in BGC. After substitution of calcium, no further tetanic seizures occurred. CONCLUSIONS Patients with BGC should be investigated for a mitochondrial disorder. A mitochondrial disorder may also manifest as tetanic seizure.

  3. Basal ganglia lesions in subacute sclerosing panencephalitis

    PubMed Central

    Almeida, Kelson James; Brucki, Sonia Maria Dozzi; Duarte, Maria Irma Seixas; Pasqualucci, Carlos Augusto Gonçalves; Rosemberg, Sérgio; Nitrini, Ricardo

    2012-01-01

    The parieto-occipital region of the brain is the most frequently and severely affected in subacute sclerosing panencephalitis (SSPE). The basal ganglia, cerebellum and corpus callosum are less commonly involved. We describe a patient with SSPE confirmed by neuropathology based on brain magnetic resonance imaging showing extensive basal ganglia involvement and no significant involvement of other cortical structures. Though rarely described in SSPE, clinicians should be aware of this involvement. SSPE should be kept in mind when changes in basal ganglia signal are seen on brain magnetic resonance imaging with or without involvement of other regions of the human brain to avoid erroneous etiological diagnosis of other pathologies causing rapidly progressive dementia. PMID:29213810

  4. Serum Fetuin-A Levels in Patients with Bilateral Basal Ganglia Calcification.

    PubMed

    Demiryurek, Bekir Enes; Gundogdu, Asli Aksoy

    2018-02-14

    The idiopathic basal ganglia calcification (Fahr syndrome) may occur due to senility. Fetuin-A is a negative acute phase reactant which inhibits calcium-phosphorus precipitation and vascular calcification. In this study, we aimed to evaluate whether serum fetuin-A levels correlate with bilateral basal ganglia calcification. Forty-five patients who had bilateral basal ganglia calcification on brain CT were selected according to the inclusion and exclusion criteria, and 45 age and gender-matched subjects without basal ganglia calcification were included for the control group. Serum fetuin-A levels were measured from venous blood samples. All participants were divided into two groups; with and without basal ganglia calcification. These groups were divided into subgroups regarding age (18-32 and 33-45 years of age) and gender (male, female). We detected lower levels of serum fetuin-A in patients with basal ganglia calcification compared with the subjects without basal ganglia calcification. In all subgroups (female, male, 18-32 years and 33-45 years), mean fetuin-A levels were significantly lower in patients with basal ganglia calcification (p = 0.017, p = 0.014, p = 0.024, p = 0.026, p = 0.01 respectively). And statistically significantly lower levels of fetuin-A was found to be correlated with the increasing densities of calcification in the calcified basal ganglia group (p-value: <0.001). Considering the role of fetuin-A in tissue calcification and inflammation, higher serum fetuin-A levels should be measured in patients with basal ganglia calcification. We believe that the measurement of serum fetuin-A may play a role in the prediction of basal ganglia calcification as a biomarker. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Biotin-responsive basal ganglia disease: neuroimaging features before and after treatment.

    PubMed

    Kassem, H; Wafaie, A; Alsuhibani, S; Farid, T

    2014-10-01

    Biotin-responsive basal ganglia disease is an autosomal recessive neurometabolic disorder presenting with subacute encephalopathy that can cause death if left untreated. The purpose of this study is to assess the neuroimaging and clinical features of the disease before and after treatment with biotin. We retrospectively reviewed the clinical, laboratory, and neuroimaging features of 15 genetically-proved Middle Eastern cases of biotin-responsive basal ganglia disease. Brain MR imaging was done at the onset of symptoms in all cases and within 2-8 weeks after biotin and thiamine therapy in 14 patients. The MR imaging datasets were analyzed according to lesion location, extent, and distribution. Brain MR imaging showed bilateral lesions in the caudate nuclei with complete or partial involvement of the putamen and sparing of the globus pallidus in all cases. In 80%, discrete abnormal signals were observed in the mesencephalon, cerebral cortical-subcortical regions, and thalami. In 53%, when the disease was advanced, patchy deep white matter affection was found. The cerebellum was involved in 13.3%. The signal abnormality of the mesencephalon, cortex, and white matter disappeared after treatment whereas the caudate and putamen necrosis persisted in all patients, including those who became asymptomatic. Biotin-responsive basal ganglia disease is a treatable underdiagnosed disease. It should be suspected in pediatric patients with unexplained encephalopathy whose brain MR imaging shows bilateral and symmetric lesions in the caudate heads and putamen, with or without involvement of mesencephalon, thalami, and cortical-subcortical regions, as the therapeutic trial of biotin and thiamine can be lifesaving. © 2014 by American Journal of Neuroradiology.

  6. Basal ganglia and Dopamine Contributions to Probabilistic Category Learning

    PubMed Central

    Shohamy, D.; Myers, C.E.; Kalanithi, J.; Gluck, M.A.

    2009-01-01

    Studies of the medial temporal lobe and basal ganglia memory systems have recently been extended towards understanding the neural systems contributing to category learning. The basal ganglia, in particular, have been linked to probabilistic category learning in humans. A separate parallel literature in systems neuroscience has emerged, indicating a role for the basal ganglia and related dopamine inputs in reward prediction and feedback processing. Here, we review behavioral, neuropsychological, functional neuroimaging, and computational studies of basal ganglia and dopamine contributions to learning in humans. Collectively, these studies implicate the basal ganglia in incremental, feedback-based learning that involves integrating information across multiple experiences. The medial temporal lobes, by contrast, contribute to rapid encoding of relations between stimuli and support flexible generalization of learning to novel contexts and stimuli. By breaking down our understanding of the cognitive and neural mechanisms contributing to different aspects of learning, recent studies are providing insight into how, and when, these different processes support learning, how they may interact with each other, and the consequence of different forms of learning for the representation of knowledge. PMID:18061261

  7. Extensive basal ganglia edema caused by a traumatic carotid-cavernous fistula: a rare presentation related to a basal vein of Rosenthal anatomical variation.

    PubMed

    Ract, Isabelle; Drier, Aurélie; Leclercq, Delphine; Sourour, Nader; Gabrieli, Joseph; Yger, Marion; Nouet, Aurélien; Dormont, Didier; Chiras, Jacques; Clarençon, Frédéric

    2014-07-01

    The authors report a very rare presentation of traumatic carotid-cavernous fistula (CCF) with extensive edema of the basal ganglia and brainstem because of an anatomical variation of the basal vein of Rosenthal (BVR). A 45-year-old woman was admitted to the authors' institution for left hemiparesis, dysarthria, and a comatose state caused by right orbital trauma from a thin metal rod. Brain MRI showed a right CCF and vasogenic edema of the right side of the brainstem, right temporal lobe, and basal ganglia. Digital subtraction angiography confirmed a high-flow direct CCF and revealed a hypoplastic second segment of the BVR responsible for the hypertension in inferior striate veins and venous congestion. Endovascular treatment was performed on an emergency basis. One month after treatment, the patient's symptoms and MRI signal abnormalities almost totally disappeared. Basal ganglia and brainstem venous congestion may occur in traumatic CCF in cases of a hypoplastic or agenetic second segment of the BVR and may provoke emergency treatment.

  8. Potential long-term effects of MDMA on the basal ganglia-thalamocortical circuit: a proton MR spectroscopy and diffusion-tensor imaging study.

    PubMed

    Liu, Hua-Shan; Chou, Ming-Chung; Chung, Hsiao-Wen; Cho, Nai-Yu; Chiang, Shih-Wei; Wang, Chao-Ying; Kao, Hung-Wen; Huang, Guo-Shu; Chen, Cheng-Yu

    2011-08-01

    To investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA, commonly known as "ecstasy") on the alterations of brain metabolites and anatomic tissue integrity related to the function of the basal ganglia-thalamocortical circuit by using proton magnetic resonance (MR) spectroscopy and diffusion-tensor MR imaging. This study was approved by a local institutional review board, and written informed consent was obtained from all subjects. Thirty-one long-term (>1 year) MDMA users and 33 healthy subjects were enrolled. Proton MR spectroscopy from the middle frontal cortex and bilateral basal ganglia and whole-brain diffusion-tensor MR imaging were performed with a 3.0-T system. Absolute concentrations of metabolites were computed, and diffusion-tensor data were registered to the International Consortium for Brain Mapping template to facilitate voxel-based group comparison. The mean myo-inositol level in the basal ganglia of MDMA users (left: 4.55 mmol/L ± 2.01 [standard deviation], right: 4.48 mmol/L ± 1.33) was significantly higher than that in control subjects (left: 3.25 mmol/L ± 1.30, right: 3.31 mmol/L ± 1.19) (P < .001). Cumulative lifetime MDMA dose showed a positive correlation with the levels of choline-containing compounds (Cho) in the right basal ganglia (r = 0.47, P = .02). MDMA users also showed a significant increase in fractional anisotropy (FA) in the bilateral thalami and significant changes in water diffusion in several regions related to the basal ganglia-thalamocortical circuit as compared with control subjects (P < .05; cluster size, >50 voxels). Increased myo-inositol and Cho concentrations in the basal ganglia of MDMA users are suggestive of glial response to degenerating serotonergic functions. The abnormal metabolic changes in the basal ganglia may consequently affect the inhibitory effect of the basal ganglia to the thalamus, as suggested by the increased FA in the thalamus and abnormal changes in water diffusion in the

  9. Cognitive-motor interactions of the basal ganglia in development

    PubMed Central

    Leisman, Gerry; Braun-Benjamin, Orit; Melillo, Robert

    2014-01-01

    Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human reasoning and adaptive function. The basal ganglia are key elements in the control of reward-based learning, sequencing, discrete elements that constitute a complete motor act, and cognitive function. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. Neuronal activity within the basal ganglia associated with motor areas of the cerebral cortex is highly correlated with parameters of movement. Neuronal activity within the basal ganglia and cerebellar loops associated with the prefrontal cortex is related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Damage to the basal ganglia of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with non-motor areas of the cortex causes higher-order deficits. In this report, we review some of the anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to attention deficit/hyperactivity disorder (ADHD

  10. Complex Dynamics in the Basal Ganglia: Health and Disease Beyond the Motor System.

    PubMed

    Andres, Daniela S; Darbin, Olivier

    2018-01-01

    The rate and oscillatory hypotheses are the two main current frameworks of basal ganglia pathophysiology. Both hypotheses have emerged from research on movement disorders sharing similar conceptualizations. These pathological conditions are classified either as hypokinetic or hyperkinetic, and the electrophysiological hallmarks of basal ganglia dysfunction are categorized as prokinetic or antikinetic. Although nonmotor symptoms, including neurobehavioral symptoms, are a key manifestation of basal ganglia dysfunction, they are uncommonly accounted for in these models. In patients with Parkinson's disease, the broad spectrum of motor symptoms and neurobehavioral symptoms challenges the concept that basal ganglia disorders can be classified into two categories. The profile of symptoms of basal ganglia dysfunction is best characterized by a breakdown of information processing, accompanied at an electrophysiological level by complex alterations of spiking activity from basal ganglia neurons. The authors argue that the dynamics of the basal ganglia circuit cannot be fully characterized by linear properties such as the firing rate or oscillatory activity. In fact, the neuronal spiking stream of the basal ganglia circuit is irregular but has temporal structure. In this context, entropy was introduced as a measure of probabilistic irregularity in the temporal organization of neuronal activity of the basal ganglia, giving place to the entropy hypothesis of basal ganglia pathology. Obtaining a quantitative characterization of irregularity of spike trains from basal ganglia neurons is key to elaborating a new framework of basal ganglia pathophysiology.

  11. Deep-Brain Stimulation for Basal Ganglia Disorders.

    PubMed

    Wichmann, Thomas; Delong, Mahlon R

    2011-07-01

    The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of 'motor' portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the 'limbic' basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders.

  12. Basal ganglia and thalamic morphology in schizophrenia and bipolar disorder.

    PubMed

    Womer, Fay Y; Wang, Lei; Alpert, Kathryn I; Smith, Matthew J; Csernansky, John G; Barch, Deanna M; Mamah, Daniel

    2014-08-30

    In this study, we examined the morphology of the basal ganglia and thalamus in bipolar disorder (BP), schizophrenia-spectrum disorders (SCZ-S), and healthy controls (HC) with particular interest in differences related to the absence or presence of psychosis. Volumetric and shape analyses of the basal ganglia and thalamus were performed in 33 BP individuals [12 without history of psychotic features (NPBP) and 21 with history of psychotic features (PBP)], 32 SCZ-S individuals [28 with SCZ and 4 with schizoaffective disorder], and 27 HC using FreeSurfer-initiated large deformation diffeomorphic metric mapping. Significant volume differences were found in the caudate and globus pallidus, with volumes smallest in the NPBP group. Shape abnormalities showing inward deformation of superior regions of the caudate were observed in BP (and especially in NPBP) compared with HC. Shape differences were also found in the globus pallidus and putamen when comparing BP and SCZ-S groups. No significant differences were seen in the nucleus accumbens and thalamus. In summary, structural abnormalities in the caudate and globus pallidus are present in BP and SCZ-S. Differences were more apparent in the NPBP subgroup. The findings herein highlight the potential importance of separately examining BP subgroups in neuroimaging studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2017-05-01

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

  14. Deep-Brain Stimulation for Basal Ganglia Disorders

    PubMed Central

    Wichmann, Thomas; DeLong, Mahlon R.

    2011-01-01

    The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of ‘motor’ portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the ‘limbic’ basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders. PMID:21804953

  15. Quantitative EEG abnormalities in major depressive disorder with basal ganglia stroke with lesions in different hemispheres.

    PubMed

    Wang, Chunfang; Chen, Yuanyuan; Zhang, Ying; Chen, Jin; Ding, Xiaojing; Ming, Dong; Du, Jingang

    2017-06-01

    This study aimed to examine the aberrant EEG oscillation in major depressive subjects with basal ganglia stroke with lesions in different hemispheres. Resting EEG of 16 electrodes in 58 stroke subjects, 26 of whom had poststroke depression (13 with left-hemisphere lesion and 13 with right) and 32 of whom did not (18 with left lesion and 14 with right), was recorded to obtain spectral power analysis for several frequency bands. Multiple analysis of variance and receiver operating characteristic (ROC) curves were used to identify differences between poststroke depression (PSD) and poststroke non-depression (PSND), treating the different lesion hemispheres separately. Moreover, Pearson linear correlation analysis was conducted to test the severity of depressive symptoms and EEG indices. PSD with left-hemisphere lesion showed increased beta2 power in frontal and central areas, but PSD with right-hemisphere lesion showed increased theta and alpha power mainly in occipital and temporal regions. Additionally, for left-hemisphere lesions, beta2 power in central and right parietal regions provided high discrimination between PSD and PSND, and for right-hemisphere lesions, theta power was similarly discriminative in most regions, especially temporal regions. We also explored the association between symptoms of depression and the power of abnormal bands, but we found no such relationship. The sample size was relatively small and included subjects with different lesions of the basal ganglia. The aberrant EEG oscillation in subjects with PSD differs between subjects with lesions of the left and right hemispheres, suggesting a complex association between depression and lesion location in stroke patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Bidirectional control of absence seizures by the basal ganglia: a computational evidence.

    PubMed

    Chen, Mingming; Guo, Daqing; Wang, Tiebin; Jing, Wei; Xia, Yang; Xu, Peng; Luo, Cheng; Valdes-Sosa, Pedro A; Yao, Dezhong

    2014-03-01

    Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. Besides the direct coupling, anatomical evidence indicates that the cerebral cortex and thalamus also communicate indirectly through an important intermediate bridge-basal ganglia. It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. Using a biophysically based model, we demonstrate here that the typical absence seizure activities can be controlled and modulated by the direct GABAergic projections from the substantia nigra pars reticulata (SNr) to either the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of thalamus, through different biophysical mechanisms. Under certain conditions, these two types of seizure control are observed to coexist in the same network. More importantly, due to the competition between the inhibitory SNr-TRN and SNr-SRN pathways, we find that both decreasing and increasing the activation of SNr neurons from the normal level may considerably suppress the generation of spike-and-slow wave discharges in the coexistence region. Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder.

  17. Bidirectional Control of Absence Seizures by the Basal Ganglia: A Computational Evidence

    PubMed Central

    Wang, Tiebin; Jing, Wei; Xia, Yang; Xu, Peng; Luo, Cheng; Valdes-Sosa, Pedro A.; Yao, Dezhong

    2014-01-01

    Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. Besides the direct coupling, anatomical evidence indicates that the cerebral cortex and thalamus also communicate indirectly through an important intermediate bridge–basal ganglia. It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. Using a biophysically based model, we demonstrate here that the typical absence seizure activities can be controlled and modulated by the direct GABAergic projections from the substantia nigra pars reticulata (SNr) to either the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of thalamus, through different biophysical mechanisms. Under certain conditions, these two types of seizure control are observed to coexist in the same network. More importantly, due to the competition between the inhibitory SNr-TRN and SNr-SRN pathways, we find that both decreasing and increasing the activation of SNr neurons from the normal level may considerably suppress the generation of spike-and-slow wave discharges in the coexistence region. Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder. PMID:24626189

  18. Parallel basal ganglia circuits for decision making.

    PubMed

    Hikosaka, Okihide; Ghazizadeh, Ali; Griggs, Whitney; Amita, Hidetoshi

    2018-03-01

    The basal ganglia control body movements, mainly, based on their values. Critical for this mechanism is dopamine neurons, which sends unpredicted value signals, mainly, to the striatum. This mechanism enables animals to change their behaviors flexibly, eventually choosing a valuable behavior. However, this may not be the best behavior, because the flexible choice is focused on recent, and, therefore, limited, experiences (i.e., short-term memories). Our old and recent studies suggest that the basal ganglia contain separate circuits that process value signals in a completely different manner. They are insensitive to recent changes in value, yet gradually accumulate the value of each behavior (i.e., movement or object choice). These stable circuits eventually encode values of many behaviors and then retain the value signals for a long time (i.e., long-term memories). They are innervated by a separate group of dopamine neurons that retain value signals, even when no reward is predicted. Importantly, the stable circuits can control motor behaviors (e.g., hand or eye) quickly and precisely, which allows animals to automatically acquire valuable outcomes based on historical life experiences. These behaviors would be called 'skills', which are crucial for survival. The stable circuits are localized in the posterior part of the basal ganglia, separately from the flexible circuits located in the anterior part. To summarize, the flexible and stable circuits in the basal ganglia, working together but independently, enable animals (and humans) to reach valuable goals in various contexts.

  19. A spiking neural network based on the basal ganglia functional anatomy.

    PubMed

    Baladron, Javier; Hamker, Fred H

    2015-07-01

    We introduce a spiking neural network of the basal ganglia capable of learning stimulus-action associations. We model learning in the three major basal ganglia pathways, direct, indirect and hyperdirect, by spike time dependent learning and considering the amount of dopamine available (reward). Moreover, we allow to learn a cortico-thalamic pathway that bypasses the basal ganglia. As a result the system develops new functionalities for the different basal ganglia pathways: The direct pathway selects actions by disinhibiting the thalamus, the hyperdirect one suppresses alternatives and the indirect pathway learns to inhibit common mistakes. Numerical experiments show that the system is capable of learning sets of either deterministic or stochastic rules. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Investigating the microstructural and neurochemical environment within the basal ganglia of current methamphetamine abusers.

    PubMed

    Lin, Joanne C; Jan, Reem K; Kydd, Rob R; Russell, Bruce R

    2015-04-01

    Methamphetamine is a highly addictive psychostimulant and the medical, social, and economic consequences associated with its use have become a major international problem. Current evidence has shown methamphetamine to be particularly neurotoxic to dopamine neurons and striatal structures within the basal ganglia. A previous study from our laboratory demonstrated larger putamen volumes in actively using methamphetamine-dependent participants. The purpose of this current study was to determine whether striatal structures in the same sample of participants also exhibit pathology on the microstructural and molecular level. Diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were carried out in current methamphetamine users (n = 18) and healthy controls (n = 22) to investigate diffusion indices and neurometabolite levels in the basal ganglia. Contrary to findings from previous DTI and MRS studies, no significant differences in diffusion indices or metabolite levels were observed in the basal ganglia regions of current methamphetamine users. These findings differ from those reported in abstinent users and the absence of diffusion and neurochemical abnormalities may suggest that striatal enlargement in current methamphetamine use may be due to mechanisms other than edema and glial proliferation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Emergence of context-dependent variability across a basal ganglia network.

    PubMed

    Woolley, Sarah C; Rajan, Raghav; Joshua, Mati; Doupe, Allison J

    2014-04-02

    Context dependence is a key feature of cortical-basal ganglia circuit activity, and in songbirds the cortical outflow of a basal ganglia circuit specialized for song, LMAN, shows striking increases in trial-by-trial variability and bursting when birds sing alone rather than to females. To reveal where this variability and its social regulation emerge, we recorded stepwise from corticostriatal (HVC) neurons and their target spiny and pallidal neurons in Area X. We find that corticostriatal and spiny neurons both show precise singing-related firing across both social settings. Pallidal neurons, in contrast, exhibit markedly increased trial-by-trial variation when birds sing alone, created by highly variable pauses in firing. This variability persists even when recurrent inputs from LMAN are ablated. These data indicate that variability and its context sensitivity emerge within the basal ganglia network, suggest a network mechanism for this emergence, and highlight variability generation and regulation as basal ganglia functions. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Emergence of context-dependent variability across a basal ganglia network

    PubMed Central

    Woolley, Sarah C.; Rajan, Raghav; Joshua, Mati; Doupe, Allison J.

    2014-01-01

    Summary Context-dependence is a key feature of cortical-basal ganglia circuit activity, and in songbirds, the cortical outflow of a basal ganglia circuit specialized for song, LMAN, shows striking increases in trial-by-trial variability and bursting when birds sing alone rather than to females. To reveal where this variability and its social regulation emerge, we recorded stepwise from cortico-striatal (HVC) neurons and their target spiny and pallidal neurons in Area X. We find that cortico-striatal and spiny neurons both show precise singing-related firing across both social settings. Pallidal neurons, in contrast, exhibit markedly increased trial-by-trial variation when birds sing alone, created by highly variable pauses in firing. This variability persists even when recurrent inputs from LMAN are ablated. These data indicate that variability and its context-sensitivity emerge within the basal ganglia network, suggest a network mechanism for this emergence, and highlight variability generation and regulation as basal ganglia functions. PMID:24698276

  3. Stimulation of serotonin2C receptors elicits abnormal oral movements by acting on pathways other than the sensorimotor one in the rat basal ganglia.

    PubMed

    Beyeler, A; Kadiri, N; Navailles, S; Boujema, M Ben; Gonon, F; Moine, C Le; Gross, C; De Deurwaerdère, P

    2010-08-11

    Serotonin2C (5-HT(2C)) receptors act in the basal ganglia, a group of sub-cortical structures involved in motor behavior, where they are thought to modulate oral activity and participate in iatrogenic motor side-effects in Parkinson's disease and Schizophrenia. Whether abnormal movements initiated by 5-HT(2C) receptors are directly consequent to dysfunctions of the motor circuit is uncertain. In the present study, we combined behavioral, immunohistochemical and extracellular single-cell recordings approaches in rats to investigate the effect of the 5-HT(2C) agonist Ro-60-0175 respectively on orofacial dyskinesia, the expression of the marker of neuronal activity c-Fos in basal ganglia and the electrophysiological activity of substantia nigra pars reticulata (SNr) neuron connected to the orofacial motor cortex (OfMC) or the medial prefrontal cortex (mPFC). The results show that Ro-60-0175 (1 mg/kg) caused bouts of orofacial movements that were suppressed by the 5-HT(2C) antagonist SB-243213 (1 mg/kg). Ro-60-0175 (0.3, 1, 3 mg/kg) dose-dependently enhanced Fos expression in the striatum and the nucleus accumbens. At the highest dose, it enhanced Fos expression in the subthalamic nucleus, the SNr and the entopeduncular nucleus but not in the external globus pallidus. However, the effect of Ro-60-0175 was mainly associated with associative/limbic regions of basal ganglia whereas subregions of basal ganglia corresponding to sensorimotor territories were devoid of Fos labeling. Ro-60-0175 (1-3 mg/kg) did not affect the electrophysiological activity of SNr neurons connected to the OfMC nor their excitatory-inhibitory-excitatory responses to the OfMC electrical stimulation. Conversely, Ro-60-0175 (1 mg/kg) enhanced the late excitatory response of SNr neurons evoked by the mPFC electrical stimulation. These results suggest that oral dyskinesia induced by 5-HT(2C) agonists are not restricted to aberrant signalling in the orofacial motor circuit and demonstrate discrete

  4. Parallel basal ganglia circuits for voluntary and automatic behaviour to reach rewards

    PubMed Central

    Hikosaka, Okihide

    2015-01-01

    The basal ganglia control body movements, value processing and decision-making. Many studies have shown that the inputs and outputs of each basal ganglia structure are topographically organized, which suggests that the basal ganglia consist of separate circuits that serve distinct functions. A notable example is the circuits that originate from the rostral (head) and caudal (tail) regions of the caudate nucleus, both of which target the superior colliculus. These two caudate regions encode the reward values of visual objects differently: flexible (short-term) values by the caudate head and stable (long-term) values by the caudate tail. These value signals in the caudate guide the orienting of gaze differently: voluntary saccades by the caudate head circuit and automatic saccades by the caudate tail circuit. Moreover, separate groups of dopamine neurons innervate the caudate head and tail and may selectively guide the flexible and stable learning/memory in the caudate regions. Studies focusing on manual handling of objects also suggest that rostrocaudally separated circuits in the basal ganglia control the action differently. These results suggest that the basal ganglia contain parallel circuits for two steps of goal-directed behaviour: finding valuable objects and manipulating the valuable objects. These parallel circuits may underlie voluntary behaviour and automatic skills, enabling animals (including humans) to adapt to both volatile and stable environments. This understanding of the functions and mechanisms of the basal ganglia parallel circuits may inform the differential diagnosis and treatment of basal ganglia disorders. PMID:25981958

  5. Lesions of basal ganglia due to disulfiram neurotoxicity.

    PubMed Central

    Laplane, D; Attal, N; Sauron, B; de Billy, A; Dubois, B

    1992-01-01

    Three cases of disulfiram induced Parkinsonism and frontal lobe-like syndrome associated with bilateral lesions of the lentiform nuclei on CT scan are reported. Symptoms developed either after an acute high dose of disulfiram (one case) or after several days to weeks of disulfiram treatment (two cases) and persisted over several years in two patients. These observations suggest that basal ganglia are one of the major targets of disulfiram neurotoxicity. The mechanisms of the lesions of basal ganglia may involve carbon disulfide toxicity. Images PMID:1431956

  6. Automated segmentation of multifocal basal ganglia T2*-weighted MRI hypointensities

    PubMed Central

    Glatz, Andreas; Bastin, Mark E.; Kiker, Alexander J.; Deary, Ian J.; Wardlaw, Joanna M.; Valdés Hernández, Maria C.

    2015-01-01

    Multifocal basal ganglia T2*-weighted (T2*w) hypointensities, which are believed to arise mainly from vascular mineralization, were recently proposed as a novel MRI biomarker for small vessel disease and ageing. These T2*w hypointensities are typically segmented semi-automatically, which is time consuming, associated with a high intra-rater variability and low inter-rater agreement. To address these limitations, we developed a fully automated, unsupervised segmentation method for basal ganglia T2*w hypointensities. This method requires conventional, co-registered T2*w and T1-weighted (T1w) volumes, as well as region-of-interest (ROI) masks for the basal ganglia and adjacent internal capsule generated automatically from T1w MRI. The basal ganglia T2*w hypointensities were then segmented with thresholds derived with an adaptive outlier detection method from respective bivariate T2*w/T1w intensity distributions in each ROI. Artefacts were reduced by filtering connected components in the initial masks based on their standardised T2*w intensity variance. The segmentation method was validated using a custom-built phantom containing mineral deposit models, i.e. gel beads doped with 3 different contrast agents in 7 different concentrations, as well as with MRI data from 98 community-dwelling older subjects in their seventies with a wide range of basal ganglia T2*w hypointensities. The method produced basal ganglia T2*w hypointensity masks that were in substantial volumetric and spatial agreement with those generated by an experienced rater (Jaccard index = 0.62 ± 0.40). These promising results suggest that this method may have use in automatic segmentation of basal ganglia T2*w hypointensities in studies of small vessel disease and ageing. PMID:25451469

  7. Basal Ganglia Perfusion in Fibromyalgia is Related to Pain Disability and Disease Impact: An Arterial Spin Labeling Study.

    PubMed

    Shokouhi, Mahsa; Davis, Karen D; Moulin, Dwight E; Morley-Forster, Pat; Nielson, Warren R; Bureau, Yves; St Lawrence, Keith

    2016-06-01

    Pain disability is a major impediment to fibromyalgia (FM) patients' quality of life. Neuroimaging studies have demonstrated abnormal pain processing in FM. However, it is not known whether there are brain abnormalities linked to pain disability. Understanding neural correlates of pain disability in FM, independent from pain intensity, could provide a framework to guide future more efficient therapy strategies to improve patients' functional ability. We used arterial spin labeling to image cerebral blood flow (CBF) in 23 FM patients and 16 controls. Functional connectivity was also estimated using blood oxygenation level-dependent imaging to further investigate the possible underpinnings of the observed CBF changes. Among patients, CBF in the basal ganglia correlated negatively with pain disability index and positively with the overall impact of FM (Fibromyalgia Impact Questionnaire) but did not correlate with pain intensity. Whole-brain analysis revealed no CBF differences between the 2 groups; however, post hoc analysis in the basal ganglia showed CBF reductions mainly in the right putamen and right lateral globus pallidus in patients, likely reflecting the negative correlation with the pain disability index. However, the connectivity of the corresponding corticobasal ganglia-thalamus loop, that is, motor network (the connection between supplementary motor area, putamen, and thalamus) remained intact. Basal ganglia perfusion reflects long-term symptoms, including somatic and psychological components of FM rather than pain intensity. These CBF findings may reflect differences in behavioral and psychological responses between patients.

  8. Basal ganglia structure in Tourette's disorder and/or attention-deficit/hyperactivity disorder.

    PubMed

    Forde, Natalie J; Zwiers, Marcel P; Naaijen, Jilly; Akkermans, Sophie E A; Openneer, Thaira J C; Visscher, Frank; Dietrich, Andrea; Buitelaar, Jan K; Hoekstra, Pieter J

    2017-04-01

    Tourette's disorder and attention-deficit/hyperactivity disorder often co-occur and have both been associated with structural variation of the basal ganglia. However, findings are inconsistent and comorbidity is often neglected. T1-weighted magnetic resonance images from children (n = 141, 8 to 12 years) with Tourette's disorder and/or attention-deficit/hyperactivity disorder and controls were processed with the Oxford Centre for Functional MRI [Magnetic resonance imaging] of the Brain (FMRIB) integrated registration and segmentation tool to determine basal ganglia nuclei volume and shape. Across all participants, basal ganglia nuclei volume and shape were estimated in relation to Tourette's disorder (categorical), attention-deficit/hyperactivity disorder severity (continuous across all participants), and their interaction. The analysis revealed no differences in basal ganglia nuclei volumes or shape between children with and without Tourette's disorder, no association with attention-deficit/hyperactivity disorder severity, and no interaction between the two. We found no evidence that Tourette's disorder, attention-deficit/hyperactivity disorder severity, or a combination thereof are associated with structural variation of the basal ganglia in 8- to 12-year-old patients. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  9. Attenuated frontal and sensory inputs to the basal ganglia in cannabis users.

    PubMed

    Blanco-Hinojo, Laura; Pujol, Jesus; Harrison, Ben J; Macià, Dídac; Batalla, Albert; Nogué, Santiago; Torrens, Marta; Farré, Magí; Deus, Joan; Martín-Santos, Rocío

    2017-07-01

    Heavy cannabis use is associated with reduced motivation. The basal ganglia, central in the motivation system, have the brain's highest cannabinoid receptor density. The frontal lobe is functionally coupled to the basal ganglia via segregated frontal-subcortical circuits conveying information from internal, self-generated activity. The basal ganglia, however, receive additional influence from the sensory system to further modulate purposeful behaviors according to the context. We postulated that cannabis use would impact functional connectivity between the basal ganglia and both internal (frontal cortex) and external (sensory cortices) sources of influence. Resting-state functional connectivity was measured in 28 chronic cannabis users and 29 controls. Selected behavioral tests included reaction time, verbal fluency and exposition to affective pictures. Assessments were repeated after one month of abstinence. Cannabis exposure was associated with (1) attenuation of the positive correlation between the striatum and areas pertaining to the 'limbic' frontal-basal ganglia circuit, and (2) attenuation of the negative correlation between the striatum and the fusiform gyrus, which is critical in recognizing significant visual features. Connectivity alterations were associated with lower arousal in response to affective pictures. Functional connectivity changes had a tendency to normalize after abstinence. The results overall indicate that frontal and sensory inputs to the basal ganglia are attenuated after chronic exposure to cannabis. This effect is consistent with the common behavioral consequences of chronic cannabis use concerning diminished responsiveness to both internal and external motivation signals. Such an impairment of the fine-tuning in the motivation system notably reverts after abstinence. © 2016 Society for the Study of Addiction.

  10. The evolutionary origin of the vertebrate basal ganglia and its role in action selection.

    PubMed

    Grillner, Sten; Robertson, Brita; Stephenson-Jones, Marcus

    2013-11-15

    The group of nuclei within the basal ganglia of the forebrain is central to the control of movement. We present data showing that the structure and function of the basal ganglia have been conserved throughout vertebrate evolution over some 560 million years. The interaction between the different nuclei within the basal ganglia is conserved as well as the cellular and synaptic properties and transmitters. We consider the role of the conserved basal ganglia circuitry for basic patterns of motor behaviour controlled via brainstem circuits. The output of the basal ganglia consists of tonically active GABAergic neurones, which target brainstem motor centres responsible for different patterns of behaviour, such as eye and locomotor movements, posture, and feeding. A prerequisite for activating or releasing a motor programme is that this GABAergic inhibition is temporarily reduced. This can be achieved through activation of GABAergic projection neurons from striatum, the input level of the basal ganglia, given an appropriate synaptic drive from cortex, thalamus and the dopamine system. The tonic inhibition of the motor centres at rest most likely serves to prevent the different motor programmes from becoming active when not intended. Striatal projection neurones are subdivided into one group with dopamine 1 receptors that provides increased excitability of the direct pathway that can initiate movements, while inhibitory dopamine 2 receptors are expressed on neurones that instead inhibit movements and are part of the 'indirect loop' in mammals as well as lamprey. We review the evidence showing that all basic features of the basal ganglia have been conserved throughout vertebrate phylogeny, and discuss these findings in relation to the role of the basal ganglia in selection of behaviour.

  11. Oscillatory activity in the basal ganglia and deep brain stimulation.

    PubMed

    Guridi, Jorge; Alegre, Manuel

    2017-01-01

    Over the past 10 years, research into the neurophysiology of the basal ganglia has provided new insights into the pathophysiology of movement disorders. The presence of pathological oscillations at specific frequencies has been linked to different signs and symptoms in PD and dystonia, suggesting a new model to explain basal ganglia dysfunction. These advances occurred in parallel with improvements in imaging and neurosurgical techniques, both of which having facilitated the more widespread use of DBS to modulate dysfunctional circuits. High-frequency stimulation is thought to disrupt pathological activity in the motor cortex/basal ganglia network; however, it is not easy to explain all of its effects based only on changes in network oscillations. In this viewpoint, we suggest that a return to classic anatomical concepts might help to understand some apparently paradoxical findings. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  12. Imaging insights into basal ganglia function, Parkinson’s disease, and dystonia

    PubMed Central

    Stoessl, A. Jon; Lehericy, Stephane; Strafella, Antonio P.

    2015-01-01

    Recent advances in structural and functional imaging have greatly improved our ability to assess normal functions of the basal ganglia, diagnose parkinsonian syndromes, understand the pathophysiology of parkinsonism and other movement disorders, and detect and monitor disease progression. Radionuclide imaging is the best way to detect and monitor dopamine deficiency, and will probably continue to be the best biomarker for assessment of the effects of disease-modifying therapies. However, advances in magnetic resonance enable the separation of patients with Parkinson’s disease from healthy controls, and show great promise for differentiation between Parkinson’s disease and other akinetic-rigid syndromes. Radionuclide imaging is useful to show the dopaminergic basis for both motor and behavioural complications of Parkinson’s disease and its treatment, and alterations in non-dopaminergic systems. Both PET and MRI can be used to study patterns of functional connectivity in the brain, which is disrupted in Parkinson’s disease and in association with its complications, and in other basal-ganglia disorders such as dystonia, in which an anatomical substrate is not otherwise apparent. Functional imaging is increasingly used to assess underlying pathological processes such as neuroinflammation and abnormal protein deposition. This imaging is another promising approach to assess the effects of treatments designed to slow disease progression. PMID:24954673

  13. Learning Reward Uncertainty in the Basal Ganglia

    PubMed Central

    Bogacz, Rafal

    2016-01-01

    Learning the reliability of different sources of rewards is critical for making optimal choices. However, despite the existence of detailed theory describing how the expected reward is learned in the basal ganglia, it is not known how reward uncertainty is estimated in these circuits. This paper presents a class of models that encode both the mean reward and the spread of the rewards, the former in the difference between the synaptic weights of D1 and D2 neurons, and the latter in their sum. In the models, the tendency to seek (or avoid) options with variable reward can be controlled by increasing (or decreasing) the tonic level of dopamine. The models are consistent with the physiology of and synaptic plasticity in the basal ganglia, they explain the effects of dopaminergic manipulations on choices involving risks, and they make multiple experimental predictions. PMID:27589489

  14. Altered Effective Connectivity Network of the Basal Ganglia in Low-Grade Hepatic Encephalopathy: A Resting-State fMRI Study with Granger Causality Analysis

    PubMed Central

    Zhong, Jianhui; Zhang, Zhiqiang; Ni, Ling; Jiao, Qing; Liao, Wei; Zheng, Gang; Lu, Guangming

    2013-01-01

    Background The basal ganglia often show abnormal metabolism and intracranial hemodynamics in cirrhotic patients with hepatic encephalopathy (HE). Little is known about how the basal ganglia affect other brain system and is affected by other brain regions in HE. The purpose of this study was to investigate whether the effective connectivity network associated with the basal ganglia is disturbed in HE patients by using resting-state functional magnetic resonance imaging (rs-fMRI). Methodology/Principal Findings Thirty five low-grade HE patients and thirty five age- and gender- matched healthy controls participated in the rs-fMRI scans. The effective connectivity networks associated with the globus pallidus, the primarily affected region within basal ganglia in HE, were characterized by using the Granger causality analysis and compared between HE patients and healthy controls. Pearson correlation analysis was performed between the abnormal effective connectivity and venous blood ammonia levels and neuropsychological performances of all HE patients. Compared with the healthy controls, patients with low-grade HE demonstrated mutually decreased influence between the globus pallidus and the anterior cingulate cortex (ACC), cuneus, bi-directionally increased influence between the globus pallidus and the precuneus, and either decreased or increased influence from and to the globus pallidus in many other frontal, temporal, parietal gyri, and cerebellum. Pearson correlation analyses revealed that the blood ammonia levels in HE patients negatively correlated with effective connectivity from the globus pallidus to ACC, and positively correlated with that from the globus pallidus to precuneus; and the number connectivity test scores in patients negatively correlated with the effective connectivity from the globus pallidus to ACC, and from superior frontal gyrus to globus pallidus. Conclusions/Significance Low-grade HE patients had disrupted effective connectivity network of

  15. Basal Ganglia Beta Oscillations Accompany Cue Utilization

    PubMed Central

    Leventhal, Daniel K.; Gage, Gregory J.; Schmidt, Robert; Pettibone, Jeffrey R.; Case, Alaina C.; Berke, Joshua D.

    2012-01-01

    SUMMARY Beta oscillations in cortical-basal ganglia (BG) circuits have been implicated in normal movement suppression and motor impairment in Parkinson’s disease. To dissect the functional correlates of these rhythms we compared neural activity during four distinct variants of a cued choice task in rats. Brief beta (~20 Hz) oscillations occurred simultaneously throughout the cortical-BG network, both spontaneously and at precise moments of task performance. Beta phase was rapidly reset in response to salient cues, yet increases in beta power were not rigidly linked to cues, movements, or movement suppression. Rather, beta power was enhanced after cues were used to determine motor output. We suggest that beta oscillations reflect a postdecision stabilized state of cortical-BG networks, which normally reduces interference from alternative potential actions. The abnormally strong beta seen in Parkinson’s Disease may reflect overstabilization of these networks, producing pathological persistence of the current motor state. PMID:22325204

  16. Basal ganglia, movement disorders and deep brain stimulation: advances made through non-human primate research.

    PubMed

    Wichmann, Thomas; Bergman, Hagai; DeLong, Mahlon R

    2018-03-01

    Studies in non-human primates (NHPs) have led to major advances in our understanding of the function of the basal ganglia and of the pathophysiologic mechanisms of hypokinetic movement disorders such as Parkinson's disease and hyperkinetic disorders such as chorea and dystonia. Since the brains of NHPs are anatomically very close to those of humans, disease states and the effects of medical and surgical approaches, such as deep brain stimulation (DBS), can be more faithfully modeled in NHPs than in other species. According to the current model of the basal ganglia circuitry, which was strongly influenced by studies in NHPs, the basal ganglia are viewed as components of segregated networks that emanate from specific cortical areas, traverse the basal ganglia, and ventral thalamus, and return to the frontal cortex. Based on the presumed functional domains of the different cortical areas involved, these networks are designated as 'motor', 'oculomotor', 'associative' and 'limbic' circuits. The functions of these networks are strongly modulated by the release of dopamine in the striatum. Striatal dopamine release alters the activity of striatal projection neurons which, in turn, influences the (inhibitory) basal ganglia output. In parkinsonism, the loss of striatal dopamine results in the emergence of oscillatory burst patterns of firing of basal ganglia output neurons, increased synchrony of the discharge of neighboring basal ganglia neurons, and an overall increase in basal ganglia output. The relevance of these findings is supported by the demonstration, in NHP models of parkinsonism, of the antiparkinsonian effects of inactivation of the motor circuit at the level of the subthalamic nucleus, one of the major components of the basal ganglia. This finding also contributed strongly to the revival of the use of surgical interventions to treat patients with Parkinson's disease. While ablative procedures were first used for this purpose, they have now been largely

  17. Deep brain stimulation changes basal ganglia output nuclei firing pattern in the dystonic hamster.

    PubMed

    Leblois, Arthur; Reese, René; Labarre, David; Hamann, Melanie; Richter, Angelika; Boraud, Thomas; Meissner, Wassilios G

    2010-05-01

    Dystonia is a heterogeneous syndrome of movement disorders characterized by involuntary muscle contractions leading to abnormal movements and postures. While medical treatment is often ineffective, deep brain stimulation (DBS) of the internal pallidum improves dystonia. Here, we studied the impact of DBS in the entopeduncular nucleus (EP), the rodent equivalent of the human globus pallidus internus, on basal ganglia output in the dt(sz)-hamster, a well-characterized model of dystonia by extracellular recordings. Previous work has shown that EP-DBS improves dystonic symptoms in dt(sz)-hamsters. We report that EP-DBS changes firing pattern in the EP, most neurons switching to a less regular firing pattern during DBS. In contrast, EP-DBS did not change the average firing rate of EP neurons. EP neurons display multiphasic responses to each stimulation impulse, likely underlying the disruption of their firing rhythm. Finally, neurons in the substantia nigra pars reticulata display similar responses to EP-DBS, supporting the idea that EP-DBS affects basal ganglia output activity through the activation of common afferent fibers. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Localization of Basal Ganglia and Thalamic Damage in Dyskinetic Cerebral Palsy.

    PubMed

    Aravamuthan, Bhooma R; Waugh, Jeff L

    2016-01-01

    Dyskinetic cerebral palsy affects 15%-20% of patients with cerebral palsy. Basal ganglia injury is associated with dyskinetic cerebral palsy, but the patterns of injury within the basal ganglia predisposing to dyskinetic cerebral palsy are unknown, making treatment difficult. For example, deep brain stimulation of the globus pallidus interna improves dystonia in only 40% of patients with dyskinetic cerebral palsy. Basal ganglia injury heterogeneity may explain this variability. To investigate this, we conducted a qualitative systematic review of basal ganglia and thalamic damage in dyskinetic cerebral palsy. Reviews and articles primarily addressing genetic or toxic causes of cerebral palsy were excluded yielding 22 studies (304 subjects). Thirteen studies specified the involved basal ganglia nuclei (subthalamic nucleus, caudate, putamen, globus pallidus, or lentiform nuclei, comprised by the putamen and globus pallidus). Studies investigating the lentiform nuclei (without distinguishing between the putamen and globus pallidus) showed that all subjects (19 of 19) had lentiform nuclei damage. Studies simultaneously but independently investigating the putamen and globus pallidus also showed that all subjects (35 of 35) had lentiform nuclei damage (i.e., putamen or globus pallidus damage); this was followed in frequency by damage to the putamen alone (70 of 101, 69%), the subthalamic nucleus (17 of 25, 68%), the thalamus (88 of 142, 62%), the globus pallidus (7/35, 20%), and the caudate (6 of 47, 13%). Globus pallidus damage was almost always coincident with putaminal damage. Noting consistent involvement of the lentiform nuclei in dyskinetic cerebral palsy, these results could suggest two groups of patients with dyskinetic cerebral palsy: those with putamen-predominant damage and those with panlenticular damage involving both the putamen and the globus pallidus. Differentiating between these groups could help predict response to therapies such as deep brain

  19. Directional analysis of coherent oscillatory field potentials in the cerebral cortex and basal ganglia of the rat

    PubMed Central

    Sharott, Andrew; Magill, Peter J; Bolam, J Paul; Brown, Peter

    2005-01-01

    Population activity in cortico-basal ganglia circuits is synchronized at different frequencies according to brain state. However, the structures that are likely to drive the synchronization of activity in these circuits remain unclear. Furthermore, it is not known whether the direction of transmission of activity is fixed or dependent on brain state. We have used the directed transfer function (DTF) to investigate the direction in which coherent activity is effectively driven in cortico-basal ganglia circuits. Local field potentials (LFPs) were simultaneously recorded in the subthalamic nucleus (STN), globus pallidus (GP) and substantia nigra pars reticulata (SNr), together with the ipsilateral frontal electrocorticogram (ECoG) of anaesthetized rats. Directional analysis was performed on recordings made during robust cortical slow-wave activity (SWA) and ‘global activation’. During SWA, there was coherence at ∼1 Hz between ECoG and basal ganglia LFPs, with much of the coherent activity directed from cortex to basal ganglia. There were similar coherent activities at ∼1 Hz within the basal ganglia, with more activity directed from SNr to GP and STN, and from STN to GP rather than vice versa. During global activation, peaks in coherent activity were seen at higher frequencies (15–60 Hz), with most coherence also directed from cortex to basal ganglia. Within the basal ganglia, however, coherence was predominantly directed from GP to STN and SNr. Together, these results highlight a lead role for the cortex in activity relationships with the basal ganglia, and further suggest that the effective direction of coupling between basal ganglia nuclei is dynamically organized according to brain state, with activity relationships involving the GP displaying the greatest capacity to change. PMID:15550466

  20. Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson's disease.

    PubMed

    Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C; Mackay, Clare E; Hu, Michele T M

    2016-08-01

    SEE POSTUMA DOI101093/AWW131 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson's disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson's disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson's disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson's disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson's disease and 10 control subjects received (123)I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye movement sleep

  1. Genetics Home Reference: biotin-thiamine-responsive basal ganglia disease

    MedlinePlus

    ... link) Biotin-Thiamine-Responsive Basal Ganglia Disease Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) THIAMINE METABOLISM DYSFUNCTION SYNDROME 2 (BIOTIN- OR THIAMINE-RESPONSIVE TYPE) ...

  2. Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome

    PubMed Central

    Arbib, Michael A.; Baldassarre, Gianluca

    2017-01-01

    Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area. PMID:28358814

  3. Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome.

    PubMed

    Caligiore, Daniele; Mannella, Francesco; Arbib, Michael A; Baldassarre, Gianluca

    2017-03-01

    Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area.

  4. Selective attentional enhancement and inhibition of fronto-posterior connectivity by the basal ganglia during attention switching.

    PubMed

    van Schouwenburg, Martine R; den Ouden, Hanneke E M; Cools, Roshan

    2015-06-01

    The prefrontal cortex and the basal ganglia interact to selectively gate a desired action. Recent studies have shown that this selective gating mechanism of the basal ganglia extends to the domain of attention. Here, we investigate the nature of this action-like gating mechanism for attention using a spatial attention-switching paradigm in combination with functional neuroimaging and dynamic causal modeling. We show that the basal ganglia guide attention by focally releasing inhibition of task-relevant representations, while simultaneously inhibiting task-irrelevant representations by selectively modulating prefrontal top-down connections. These results strengthen and specify the role of the basal ganglia in attention. Moreover, our findings have implications for psychological theorizing by suggesting that inhibition of unattended sensory regions is not only a consequence of mutual suppression, but is an active process, subserved by the basal ganglia. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Proactive Selective Response Suppression Is Implemented via the Basal Ganglia

    PubMed Central

    Majid, D. S. Adnan; Cai, Weidong; Corey-Bloom, Jody

    2013-01-01

    In the welter of everyday life, people can stop particular response tendencies without affecting others. A key requirement for such selective suppression is that subjects know in advance which responses need stopping. We hypothesized that proactively setting up and implementing selective suppression relies on the basal ganglia and, specifically, regions consistent with the inhibitory indirect pathway for which there is scant functional evidence in humans. Consistent with this hypothesis, we show, first, that the degree of proactive motor suppression when preparing to stop selectively (indexed by transcranial magnetic stimulation) corresponds to striatal, pallidal, and frontal activation (indexed by functional MRI). Second, we demonstrate that greater striatal activation at the time of selective stopping correlates with greater behavioral selectivity. Third, we show that people with striatal and pallidal volume reductions (those with premanifest Huntington's disease) have both absent proactive motor suppression and impaired behavioral selectivity when stopping. Thus, stopping goals are used to proactively set up specific basal ganglia channels that may then be triggered to implement selective suppression. By linking this suppression to the striatum and pallidum, these results provide compelling functional evidence in humans of the basal ganglia's inhibitory indirect pathway. PMID:23946385

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

    PubMed Central

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

    2014-01-01

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

  7. Infantile Basal Ganglia Stroke after Mild Head Trauma Associated with Mineralizing Angiopathy of Lenticulostriate Arteries: An Under Recognized Entity.

    PubMed

    Toelle, Sandra P; Avetisyan, Tamara; Kuyumjyan, Nune; Sukhudyan, Biayna; Boltshauser, Eugen; Hackenberg, Annette

    2018-05-23

    Basal ganglia infarction in young children, mostly after mild head trauma, has been repeatedly reported. The pathogenesis and the risk factors are not fully understood. Lenticulostriate vasculopathy, usually referred to as basal ganglia calcification, is discussed as one of them. We describe five young (7-13 months old on presentation) male children who suffered from hemiparesis due to ischemic stroke of the basal ganglia, four of them after minor head trauma. All of them had calcification in the basal ganglia visible on computed tomography or cranial ultrasound but not on magnetic resonance imaging. Follow-up care was remarkable for recurrent infarction in three patients. One patient had a second symptomatic stroke on the contralateral side, and two patients showed new asymptomatic infarctions in the contralateral basal ganglia on imaging. In view of the scant literature, this clinic-radiologic entity seems under recognized. We review the published cases and hypothesize that male sex and iron deficiency anemia are risk factors for basal ganglia stroke after minor trauma in the context of basal ganglia calcification in infants. We suggest to perform appropriate targeted neuroimaging in case of infantile basal ganglia stroke, and to consider prophylactic medical treatment, although its value in this context is not proven. Georg Thieme Verlag KG Stuttgart · New York.

  8. Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex.

    PubMed

    Caligiore, Daniele; Pezzulo, Giovanni; Baldassarre, Gianluca; Bostan, Andreea C; Strick, Peter L; Doya, Kenji; Helmich, Rick C; Dirkx, Michiel; Houk, James; Jörntell, Henrik; Lago-Rodriguez, Angel; Galea, Joseph M; Miall, R Chris; Popa, Traian; Kishore, Asha; Verschure, Paul F M J; Zucca, Riccardo; Herreros, Ivan

    2017-02-01

    Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.

  9. Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson’s disease

    PubMed Central

    Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A.; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A.; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C.; Mackay, Clare E.

    2016-01-01

    Abstract See Postuma (doi:10.1093/aww131) for a scientific commentary on this article. Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson’s disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson’s disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson’s disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson’s disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson’s disease and 10 control subjects received 123I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye

  10. The Pedunculopontine Tegmental Nucleus as a Motor and Cognitive Interface between the Cerebellum and Basal Ganglia.

    PubMed

    Mori, Fumika; Okada, Ken-Ichi; Nomura, Taishin; Kobayashi, Yasushi

    2016-01-01

    As an important component of ascending activating systems, brainstem cholinergic neurons in the pedunculopontine tegmental nucleus (PPTg) are involved in the regulation of motor control (locomotion, posture and gaze) and cognitive processes (attention, learning and memory). The PPTg is highly interconnected with several regions of the basal ganglia, and one of its key functions is to regulate and relay activity from the basal ganglia. Together, they have been implicated in the motor control system (such as voluntary movement initiation or inhibition), and modulate aspects of executive function (such as motivation). In addition to its intimate connection with the basal ganglia, projections from the PPTg to the cerebellum have been recently reported to synaptically activate the deep cerebellar nuclei. Classically, the cerebellum and basal ganglia were regarded as forming separated anatomical loops that play a distinct functional role in motor and cognitive behavioral control. Here, we suggest that the PPTg may also act as an interface device between the basal ganglia and cerebellum. As such, part of the therapeutic effect of PPTg deep brain stimulation (DBS) to relieve gait freezing and postural instability in advanced Parkinson's disease (PD) patients might also involve modulation of the cerebellum. We review the anatomical position and role of the PPTg in the pathway of basal ganglia and cerebellum in relation to motor control, cognitive function and PD.

  11. Altered basal ganglia-cortical functional connections in frontal lobe epilepsy: A resting-state fMRI study.

    PubMed

    Dong, Li; Wang, Pu; Peng, Rui; Jiang, Sisi; Klugah-Brown, Benjamin; Luo, Cheng; Yao, Dezhong

    2016-12-01

    The purpose of this study was to investigate alterations of basal ganglia-cortical functional connections in patients with frontal lobe epilepsy (FLE). Resting-state functional magnetic resonance imaging (fMRI) data were gathered from 19 FLE patients and 19 age- and gender-matched healthy controls. Functional connectivity (FC) analysis was used to assess the functional connections between basal ganglia and cerebral cortex. Regions of interest, including the left/right caudate, putamen, pallidum and thalamus, were selected as the seeds. Two sample t-test was used to determine the difference between patients and controls, while controlling the age, gender and head motions. Compared with controls, FLE patients demonstrated increased FCs between basal ganglia and regions including the right fusiform gyrus, the bilateral cingulate gyrus, the precuneus and anterior cingulate gyrus. Reduced FCs were mainly located in a range of brain regions including the bilateral middle occipital gyrus, the ventral frontal lobe, the right putamen, the left fusiform gyrus and right rolandic operculum. In addition, the relationships between basal ganglia-cingulate connections and durations of epilepsy were also found. The alterations of functional integrity within the basal ganglia, as well as its connections to limbic and ventral frontal areas, indicate the important roles of the basal ganglia-cortical functional connections in FLE, and provide new insights in the pathophysiological mechanism of FLE. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Opponent and bidirectional control of movement velocity in the basal ganglia

    PubMed Central

    Yttri, Eric A.

    2016-01-01

    For goal-directed behavior it is critical that we can both select the appropriate action and learn to modify the underlying movements (e.g. the pitch of a note or velocity of a reach) to improve outcomes. The basal ganglia are a critical nexus where circuits necessary for the production of behavior, such as neocortex and thalamus, are integrated with reward signaling 1 to reinforce successful, purposive actions 2. Dorsal striatum, a major input structure of basal ganglia is composed of two opponent pathways, direct and indirect, thought to select actions that elicit positive outcomes or suppress actions that do not, respectively 3,4. Activity-dependent plasticity modulated by reward is thought to be sufficient for selecting actions in striatum 5,6. Although perturbations of basal ganglia function produce profound changes in movement 7, it remains unknown whether activity-dependent plasticity is sufficient to produce learned changes in movement kinematics, such as velocity. Here we used cell-type specific stimulation delivered in closed-loop during movement to demonstrate that activity in either the direct or indirect pathway is sufficient to produce specific and sustained increases or decreases in velocity without affecting action selection or motivation. These behavioral changes were a form of learning that accumulated over trials, persisted after the cessation of stimulation, and were abolished in the presence of dopamine antagonists. Our results reveal that the direct and indirect pathways can each bidirectionally control movement velocity, demonstrating unprecedented specificity and flexibility in the control of volition by the basal ganglia. PMID:27135927

  13. Dissociating hippocampal and basal ganglia contributions to category learning using stimulus novelty and subjective judgments

    PubMed Central

    Seger, Carol A.; Dennison, Christina S.; Lopez-Paniagua, Dan; Peterson, Erik J.; Roark, Aubrey A.

    2011-01-01

    We identified factors leading to hippocampal and basal ganglia recruitment during categorization learning. Subjects alternated between blocks of a standard trial and error category learning task and a subjective judgment task. In the subjective judgments task subjects categorized the stimulus and then instead of receiving feedback they indicated the basis of their response using 4 options: Remember: Conscious episodic memory of previous trials. Know-Automatic: Automatic, rapid response accompanied by conscious awareness of category membership. Know-Intuition: A “gut feeling” without fully conscious knowledge of category membership. Guess: Guessing. In addition, new stimuli were introduced throughout the experiment to examine effects of novelty. Categorization overall recruited both the basal ganglia and posterior hippocampus. However, basal ganglia activity was found during Know judgments (both Automatic and Intuition), whereas posterior hippocampus activity was found during Remember judgments. Granger causality mapping indicated interactions between the basal ganglia and hippocampus, with the putamen exerting directed influence on the posterior hippocampus, which in turn exerted directed influence on the posterior caudate nucleus. We also found a region of anterior hippocampus that showed decreased activity relative to baseline during categorization overall, and showed a strong novelty effect. Our results indicate that subjective measures may be effective in dissociating basal ganglia from hippocampal dependent learning, and that the basal ganglia are involved in both conscious and unconscious learning. They also indicate a dissociation within the hippocampus, in which the anterior regions are sensitive to novelty, and the posterior regions are involved in memory based categorization learning. PMID:21255655

  14. Cytokine effects on the basal ganglia and dopamine function: the subcortical source of inflammatory malaise.

    PubMed

    Felger, Jennifer C; Miller, Andrew H

    2012-08-01

    Data suggest that cytokines released during the inflammatory response target subcortical structures including the basal ganglia as well as dopamine function to acutely induce behavioral changes that support fighting infection and wound healing. However, chronic inflammation and exposure to inflammatory cytokines appears to lead to persisting alterations in the basal ganglia and dopamine function reflected by anhedonia, fatigue, and psychomotor slowing. Moreover, reduced neural responses to hedonic reward, decreased dopamine metabolites in the cerebrospinal fluid and increased presynaptic dopamine uptake and decreased turnover have been described. This multiplicity of changes in the basal ganglia and dopamine function suggest fundamental effects of inflammatory cytokines on dopamine synthesis, packaging, release and/or reuptake, which may sabotage and circumvent the efficacy of current treatment approaches. Thus, examination of the mechanisms by which cytokines alter the basal ganglia and dopamine function will yield novel insights into the treatment of cytokine-induced behavioral changes and inflammatory malaise. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Investigating Synchronous Oscillation and Deep Brain Stimulation Treatment in A Model of Cortico-Basal Ganglia Network.

    PubMed

    Lu, Meili; Wei, Xile; Loparo, Kenneth A

    2017-11-01

    Altered firing properties and increased pathological oscillations in the basal ganglia have been proven to be hallmarks of Parkinson's disease (PD). Increasing evidence suggests that abnormal synchronous oscillations and suppression in the cortex may also play a critical role in the pathogenic process and treatment of PD. In this paper, a new closed-loop network including the cortex and basal ganglia using the Izhikevich models is proposed to investigate the synchrony and pathological oscillations in motor circuits and their modulation by deep brain stimulation (DBS). Results show that more coherent dynamics in the cortex may cause stronger effects on the synchrony and pathological oscillations of the subthalamic nucleus (STN). The pathological beta oscillations of the STN can both be efficiently suppressed with DBS applied directly to the STN or to cortical neurons, respectively, but the underlying mechanisms by which DBS suppresses the beta oscillations are different. This research helps to understand the dynamics of pathological oscillations in PD-related motor regions and supports the therapeutic potential of stimulation of cortical neurons.

  16. Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

    PubMed Central

    Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

    2015-01-01

    In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation (DBS) therapy. PMID:25698937

  17. Nigrostriatal lesion induces D2-modulated phase-locked activity in the basal ganglia of rats.

    PubMed

    Zold, Camila L; Ballion, Bérangère; Riquelme, Luis A; Gonon, François; Murer, M Gustavo

    2007-04-01

    There is a debate as to what modifications of neuronal activity underlie the clinical manifestations of Parkinson's disease and the efficacy of antiparkinsonian pharmacotherapy. Previous studies suggest that release of GABAergic striatopallidal neurons from D2 receptor-mediated inhibition allows spreading of cortical rhythms to the globus pallidus (GP) in rats with 6-hydroxydopamine-induced nigrostriatal lesions. Here this abnormal spreading was thoroughly investigated. In control urethane-anaesthetized rats most GP neurons were excited during the active part of cortical slow waves ('direct-phase' neurons). Two neuronal populations having opposite phase relationships with cortical and striatal activity coexisted in the GP of 6-hydroxydopamine-lesioned rats. 'Inverse-phase' GP units exhibited reduced firing coupled to striatal activation during slow waves, suggesting that this GP oscillation was driven by striatopallidal hyperactivity. Half of the pallidonigral neurons identified by antidromic stimulation exhibited inverse-phase activity. Therefore, spreading of inverse-phase oscillations through pallidonigral axons might contribute to the abnormal direct-phase cortical entrainment of basal ganglia output described previously. Systemic administration of the D2 agonist quinpirole to 6-hydroxydopamine-lesioned rats reduced GP inverse-phase coupling with slow waves, and this effect was reversed by the D2 antagonist eticlopride. Because striatopallidal hyperactivity was only slightly reduced by quinpirole, other mechanisms might have contributed to the effect of quinpirole on GP oscillations. These results suggest that antiparkinsonian efficacy may rely on other actions of D2 agonists on basal ganglia activity. However, abnormal slow rhythms may promote enduring changes in functional connectivity along the striatopallidal axis, contributing to D2 agonist-resistant clinical signs of parkinsonism.

  18. How may the basal ganglia contribute to auditory categorization and speech perception?

    PubMed Central

    Lim, Sung-Joo; Fiez, Julie A.; Holt, Lori L.

    2014-01-01

    Listeners must accomplish two complementary perceptual feats in extracting a message from speech. They must discriminate linguistically-relevant acoustic variability and generalize across irrelevant variability. Said another way, they must categorize speech. Since the mapping of acoustic variability is language-specific, these categories must be learned from experience. Thus, understanding how, in general, the auditory system acquires and represents categories can inform us about the toolbox of mechanisms available to speech perception. This perspective invites consideration of findings from cognitive neuroscience literatures outside of the speech domain as a means of constraining models of speech perception. Although neurobiological models of speech perception have mainly focused on cerebral cortex, research outside the speech domain is consistent with the possibility of significant subcortical contributions in category learning. Here, we review the functional role of one such structure, the basal ganglia. We examine research from animal electrophysiology, human neuroimaging, and behavior to consider characteristics of basal ganglia processing that may be advantageous for speech category learning. We also present emerging evidence for a direct role for basal ganglia in learning auditory categories in a complex, naturalistic task intended to model the incidental manner in which speech categories are acquired. To conclude, we highlight new research questions that arise in incorporating the broader neuroscience research literature in modeling speech perception, and suggest how understanding contributions of the basal ganglia can inform attempts to optimize training protocols for learning non-native speech categories in adulthood. PMID:25136291

  19. The Development of the Basal Ganglia in Capuchin Monkeys (Cebus apella)

    PubMed Central

    Phillips, Kimberley A.; Sobieski, Courtney A.; Gilbert, Valerie R.; Chiappini-Williamson, Christine; Sherwood, Chet C.; Strick, Peter L.

    2010-01-01

    The basal ganglia are subcortical structures involved in the planning, initiation and regulation of movement as well as a variety of non-motor, cognitive and affective functions. Capuchin monkeys share several important characteristics of development with humans, including a prolonged infancy and juvenile period, a long lifespan, and complex manipulative abilities. This makes capuchins important comparative models for understanding age-related neuroanatomical changes in these structures. Here we report developmental volumetric data on the three subdivisions of the basal ganglia, the caudate, putamen and globus pallidus in brown capuchin monkeys (Cebus apella). Based on a cross-sectional sample, we describe brain development in 28 brown capuchin monkeys (male n = 17, female n = 11; age range = 2 months – 20 years) using high-resolution structural MRI. We found that the raw volumes of the putamen and caudate varied significantly with age, decreasing in volume from birth through early adulthood. Notably, developmental changes did not differ between sexes. Because these observed developmental patterns are similar to humans, our results suggest that capuchin monkeys may be useful animal models for investigating neurodevelopmental disorders of the basal ganglia. PMID:20227397

  20. Mössbauer spectroscopy of Basal Ganglia

    NASA Astrophysics Data System (ADS)

    Miglierini, Marcel; Lančok, Adriana; Kopáni, Martin; Boča, Roman

    2014-10-01

    Chemical states, structural arrangement, and magnetic features of iron deposits in biological tissue of Basal Ganglia are characterized. The methods of SQUID magnetometry and electron microscopy are employed. 57Fe Mössbauer spectroscopy is used as a principal method of investigation. Though electron microscopy has unveiled robust crystals (1-3 μm in size) of iron oxides, they are not manifested in the corresponding 57Fe Mössbauer spectra. The latter were acquired at 300 K and 4.2 K and resemble ferritin-like behavior.

  1. Mössbauer spectroscopy of Basal Ganglia

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

    Miglierini, Marcel, E-mail: marcel.miglierini@stuba.sk; Lančok, Adriana; Kopáni, Martin

    2014-10-27

    Chemical states, structural arrangement, and magnetic features of iron deposits in biological tissue of Basal Ganglia are characterized. The methods of SQUID magnetometry and electron microscopy are employed. {sup 57}Fe Mössbauer spectroscopy is used as a principal method of investigation. Though electron microscopy has unveiled robust crystals (1-3 μm in size) of iron oxides, they are not manifested in the corresponding {sup 57}Fe Mössbauer spectra. The latter were acquired at 300 K and 4.2 K and resemble ferritin-like behavior.

  2. Goal-directed and habitual control in the basal ganglia: implications for Parkinson’s disease

    PubMed Central

    Redgrave, Peter; Rodriguez, Manuel; Smith, Yoland; Rodriguez-Oroz, Maria C.; Lehericy, Stephane; Bergman, Hagai; Agid, Yves; DeLong, Mahlon R.; Obeso, Jose A.

    2011-01-01

    Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson’s disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson’s disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. PMID:20944662

  3. Symmetrical and bilateral basal ganglia calcification. Case series and literature review.

    PubMed

    Jiménez-Ruiz, Amado; Cárdenas-Sáenz, Omar; Ruiz-Sandoval, José Luis

    2018-01-01

    Symmetric, bilateral basal ganglia calcification is rare finding that sometimes occurs asymptomatically. Its prevalence increases with age, and the most affected site is the globus pallidus. A series of seven cases with clinical and imaging diagnosis of basal ganglia calcification, recorded during the 2012 to 2016 period at the Department of Internal Medicine of the Hospital Civil de Guadalajara "Fray Antonio Alcalde, is presented. Most common clinical presentation was with altered alertness, headache and seizures. There was one case with movement disorders; there were no cases identified with dementia or tetany. Ganglia calcification can be associated with age-related neurodegenerative changes, but it can be an initial manifestation of a variety of systemic pathologies, including disorders of the calcium metabolism, intoxication by different agents, and autoimmune and genetic diseases. Correlation of typical imaging findings with clinical manifestations and laboratory results should be established to reach a definitive judgment. Copyright: © 2018 SecretarÍa de Salud.

  4. The inhibitory microcircuit of the substantia nigra provides feedback gain control of the basal ganglia output

    PubMed Central

    Brown, Jennifer; Pan, Wei-Xing; Dudman, Joshua Tate

    2014-01-01

    Dysfunction of the basal ganglia produces severe deficits in the timing, initiation, and vigor of movement. These diverse impairments suggest a control system gone awry. In engineered systems, feedback is critical for control. By contrast, models of the basal ganglia highlight feedforward circuitry and ignore intrinsic feedback circuits. In this study, we show that feedback via axon collaterals of substantia nigra projection neurons control the gain of the basal ganglia output. Through a combination of physiology, optogenetics, anatomy, and circuit mapping, we elaborate a general circuit mechanism for gain control in a microcircuit lacking interneurons. Our data suggest that diverse tonic firing rates, weak unitary connections and a spatially diffuse collateral circuit with distinct topography and kinetics from feedforward input is sufficient to implement divisive feedback inhibition. The importance of feedback for engineered systems implies that the intranigral microcircuit, despite its absence from canonical models, could be essential to basal ganglia function. DOI: http://dx.doi.org/10.7554/eLife.02397.001 PMID:24849626

  5. Social context differentially modulates activity of two interneuron populations in an avian basal ganglia nucleus

    PubMed Central

    2016-01-01

    Basal ganglia circuits are critical for the modulation of motor performance across behavioral states. In zebra finches, a cortical-basal ganglia circuit dedicated to singing is necessary for males to adjust their song performance and transition between spontaneous singing, when they are alone (“undirected” song), and a performance state, when they sing to a female (“female-directed” song). However, we know little about the role of different basal ganglia cell types in this behavioral transition or the degree to which behavioral context modulates the activity of different neuron classes. To investigate whether interneurons in the songbird basal ganglia encode information about behavioral state, I recorded from two interneuron types, fast-spiking interneurons (FSI) and external pallidal (GPe) neurons, in the songbird basal ganglia nucleus area X during both female-directed and undirected singing. Both cell types exhibited higher firing rates, more frequent bursting, and greater trial-by-trial variability in firing when male zebra finches produced undirected songs compared with when they produced female-directed songs. However, the magnitude and direction of changes to the firing rate, bursting, and variability of spiking between when birds sat silently and when they sang undirected and female-directed song varied between FSI and GPe neurons. These data indicate that social modulation of activity important for eliciting changes in behavioral state is present in multiple cell types within area X and suggests that social interactions may adjust circuit dynamics during singing at multiple points within the circuit. PMID:27628208

  6. Canceling actions involves a race between basal ganglia pathways

    PubMed Central

    Schmidt, Robert; Leventhal, Daniel K.; Mallet, Nicolas; Chen, Fujun; Berke, Joshua D.

    2013-01-01

    Salient cues can prompt the rapid interruption of planned actions. It has been proposed that fast, reactive behavioral inhibition involves specific basal ganglia pathways, and we tested this by comparing activity in multiple rat basal ganglia structures during performance of a stop-signal task. Subthalamic nucleus (STN) neurons showed low-latency responses to Stop cues, irrespective of whether actions were successfully canceled or not. By contrast, neurons downstream in the substantia nigra pars reticulata (SNr) responded to Stop cues only in trials with successful cancellation. Recordings and simulations together indicate that this sensorimotor gating arises from the relative timing of two distinct inputs to neurons in the SNr dorsolateral “core” subregion: cue-related excitation from STN and movement-related inhibition from striatum. Our results support race models of action cancellation, with successful stopping requiring Stop cue information to be transmitted from STN to SNr before increased striatal input creates a point of no return. PMID:23852117

  7. Morphological elucidation of basal ganglia circuits contributing reward prediction

    PubMed Central

    Fujiyama, Fumino; Takahashi, Susumu; Karube, Fuyuki

    2015-01-01

    Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits. The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor–critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. PMID:25698913

  8. Basal Ganglia Neuromodulation Over Multiple Temporal and Structural Scales—Simulations of Direct Pathway MSNs Investigate the Fast Onset of Dopaminergic Effects and Predict the Role of Kv4.2

    PubMed Central

    Lindroos, Robert; Dorst, Matthijs C.; Du, Kai; Filipović, Marko; Keller, Daniel; Ketzef, Maya; Kozlov, Alexander K.; Kumar, Arvind; Lindahl, Mikael; Nair, Anu G.; Pérez-Fernández, Juan; Grillner, Sten; Silberberg, Gilad; Hellgren Kotaleski, Jeanette

    2018-01-01

    The basal ganglia are involved in the motivational and habitual control of motor and cognitive behaviors. Striatum, the largest basal ganglia input stage, integrates cortical and thalamic inputs in functionally segregated cortico-basal ganglia-thalamic loops, and in addition the basal ganglia output nuclei control targets in the brainstem. Striatal function depends on the balance between the direct pathway medium spiny neurons (D1-MSNs) that express D1 dopamine receptors and the indirect pathway MSNs that express D2 dopamine receptors. The striatal microstructure is also divided into striosomes and matrix compartments, based on the differential expression of several proteins. Dopaminergic afferents from the midbrain and local cholinergic interneurons play crucial roles for basal ganglia function, and striatal signaling via the striosomes in turn regulates the midbrain dopaminergic system directly and via the lateral habenula. Consequently, abnormal functions of the basal ganglia neuromodulatory system underlie many neurological and psychiatric disorders. Neuromodulation acts on multiple structural levels, ranging from the subcellular level to behavior, both in health and disease. For example, neuromodulation affects membrane excitability and controls synaptic plasticity and thus learning in the basal ganglia. However, it is not clear on what time scales these different effects are implemented. Phosphorylation of ion channels and the resulting membrane effects are typically studied over minutes while it has been shown that neuromodulation can affect behavior within a few hundred milliseconds. So how do these seemingly contradictory effects fit together? Here we first briefly review neuromodulation of the basal ganglia, with a focus on dopamine. We furthermore use biophysically detailed multi-compartmental models to integrate experimental data regarding dopaminergic effects on individual membrane conductances with the aim to explain the resulting cellular level

  9. Basal ganglia and cerebellar interconnectivity within the human thalamus.

    PubMed

    Pelzer, Esther A; Melzer, Corina; Timmermann, Lars; von Cramon, D Yves; Tittgemeyer, Marc

    2017-01-01

    Basal ganglia and the cerebellum are part of a densely interconnected network. While both subcortical structures process information in basically segregated loops that primarily interact in the neocortex, direct subcortical interaction has been recently confirmed by neuroanatomical studies using viral transneuronal tracers in non-human primate brains. The thalamus is thought to be the main relay station of both projection systems. Yet, our understanding of subcortical basal ganglia and cerebellar interconnectivity within the human thalamus is rather sparse, primarily due to limitation in the acquisition of in vivo tracing. Consequently, we strive to characterize projections of both systems and their potential overlap within the human thalamus by diffusion MRI and tractography. Our analysis revealed a decreasing anterior-to-posterior gradient for pallido-thalamic connections in: (1) the ventral-anterior thalamus, (2) the intralaminar nuclei, and (3) midline regions. Conversely, we found a decreasing posterior-to-anterior gradient for dentato-thalamic projections predominantly in: (1) the ventral-lateral and posterior nucleus; (2) dorsal parts of the intralaminar nuclei and the subparafascicular nucleus, and (3) the medioventral and lateral mediodorsal nucleus. A considerable overlap of connectivity pattern was apparent in intralaminar nuclei and midline regions. Notably, pallidal and cerebellar projections were both hemispherically lateralized to the left thalamus. While strikingly consistent with findings from transneuronal studies in non-human primates as well as with pre-existing anatomical studies on developmentally expressed markers or pathological human brains, our assessment provides distinctive connectional fingerprints that illustrate the anatomical substrate of integrated functional networks between basal ganglia and the cerebellum. Thereby, our findings furnish useful implications for cerebellar contributions to the clinical symptomatology of movement

  10. Multisensory integration in the basal ganglia.

    PubMed

    Nagy, Attila; Eördegh, Gabriella; Paróczy, Zsuzsanna; Márkus, Zita; Benedek, György

    2006-08-01

    Sensorimotor co-ordination in mammals is achieved predominantly via the activity of the basal ganglia. To investigate the underlying multisensory information processing, we recorded the neuronal responses in the caudate nucleus (CN) and substantia nigra (SN) of anaesthetized cats to visual, auditory or somatosensory stimulation alone and also to their combinations, i.e. multisensory stimuli. The main goal of the study was to ascertain whether multisensory information provides more information to the neurons than do the individual sensory components. A majority of the investigated SN and CN multisensory units exhibited significant cross-modal interactions. The multisensory response enhancements were either additive or superadditive; multisensory response depressions were also detected. CN and SN cells with facilitatory and inhibitory interactions were found in each multisensory combination. The strengths of the multisensory interactions did not differ in the two structures. A significant inverse correlation was found between the strengths of the best unimodal responses and the magnitudes of the multisensory response enhancements, i.e. the neurons with the weakest net unimodal responses exhibited the strongest enhancement effects. The onset latencies of the responses of the integrative CN and SN neurons to the multisensory stimuli were significantly shorter than those to the unimodal stimuli. These results provide evidence that the multisensory CN and SN neurons, similarly to those in the superior colliculus and related structures, have the ability to integrate multisensory information. Multisensory integration may help in the effective processing of sensory events and the changes in the environment during motor actions controlled by the basal ganglia.

  11. Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation.

    PubMed

    Da Cunha, Claudio; Boschen, Suelen L; Gómez-A, Alexander; Ross, Erika K; Gibson, William S J; Min, Hoon-Ki; Lee, Kendall H; Blaha, Charles D

    2015-11-01

    This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson's disease, Huntington's disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. MR-DTI and PET multimodal imaging of dopamine release within subdivisions of basal ganglia

    NASA Astrophysics Data System (ADS)

    Tziortzi, A.; Searle, G.; Tsoumpas, C.; Long, C.; Shotbolt, P.; Rabiner, E.; Jenkinson, M.; Gunn, R. N.

    2011-09-01

    The basal ganglia is a group of anatomical nuclei, functionally organised into limbic, associative and sensorimotor regions, which plays a central role in dopamine related neurological and psychiatric disorders. In this study, we combine two imaging modalities to enable the measurement of dopamine release in functionally related subdivisions of the basal ganglia. [11C]-(+)-PHNO Positron Emission Tomography (PET) measurements in the living human brain pre- and post-administration of amphetamine allow for the estimation of regional dopamine release. Combined Magnetic Resonance Diffusion Tensor Imaging (MR-DTI) data allows for the definition of functional territories of the basal ganglia from connectivity information. The results suggest that there is a difference in dopamine release among the connectivity derived functional subdivisions. Dopamine release is highest in the limbic area followed by the sensorimotor and then the associative area with this pattern reflected in both striatum and pallidum.

  13. Neuroanatomical correlates of intelligence in healthy young adults: the role of basal ganglia volume.

    PubMed

    Rhein, Cosima; Mühle, Christiane; Richter-Schmidinger, Tanja; Alexopoulos, Panagiotis; Doerfler, Arnd; Kornhuber, Johannes

    2014-01-01

    In neuropsychiatric diseases with basal ganglia involvement, higher cognitive functions are often impaired. In this exploratory study, we examined healthy young adults to gain detailed insight into the relationship between basal ganglia volume and cognitive abilities under non-pathological conditions. We investigated 137 healthy adults that were between the ages of 21 and 35 years with similar educational backgrounds. Magnetic resonance imaging (MRI) was performed, and volumes of basal ganglia nuclei in both hemispheres were calculated using FreeSurfer software. The cognitive assessment consisted of verbal, numeric and figural aspects of intelligence for either the fluid or the crystallised intelligence factor using the intelligence test Intelligenz-Struktur-Test (I-S-T 2000 R). Our data revealed significant correlations of the caudate nucleus and pallidum volumes with figural and numeric aspects of intelligence, but not with verbal intelligence. Interestingly, figural intelligence associations were dependent on sex and intelligence factor; in females, the pallidum volumes were correlated with crystallised figural intelligence (r = 0.372, p = 0.01), whereas in males, the caudate volumes were correlated with fluid figural intelligence (r = 0.507, p = 0.01). Numeric intelligence was correlated with right-lateralised caudate nucleus volumes for both females and males, but only for crystallised intelligence (r = 0.306, p = 0.04 and r = 0.459, p = 0.04, respectively). The associations were not mediated by prefrontal cortical subfield volumes when controlling with partial correlation analyses. The findings of our exploratory analysis indicate that figural and numeric intelligence aspects, but not verbal aspects, are strongly associated with basal ganglia volumes. Unlike numeric intelligence, the type of figural intelligence appears to be related to distinct basal ganglia nuclei in a sex-specific manner. Subcortical brain structures thus may contribute substantially to

  14. Neuroanatomical Correlates of Intelligence in Healthy Young Adults: The Role of Basal Ganglia Volume

    PubMed Central

    Rhein, Cosima; Mühle, Christiane; Richter-Schmidinger, Tanja; Alexopoulos, Panagiotis; Doerfler, Arnd; Kornhuber, Johannes

    2014-01-01

    Background In neuropsychiatric diseases with basal ganglia involvement, higher cognitive functions are often impaired. In this exploratory study, we examined healthy young adults to gain detailed insight into the relationship between basal ganglia volume and cognitive abilities under non-pathological conditions. Methodology/Principal Findings We investigated 137 healthy adults that were between the ages of 21 and 35 years with similar educational backgrounds. Magnetic resonance imaging (MRI) was performed, and volumes of basal ganglia nuclei in both hemispheres were calculated using FreeSurfer software. The cognitive assessment consisted of verbal, numeric and figural aspects of intelligence for either the fluid or the crystallised intelligence factor using the intelligence test Intelligenz-Struktur-Test (I-S-T 2000 R). Our data revealed significant correlations of the caudate nucleus and pallidum volumes with figural and numeric aspects of intelligence, but not with verbal intelligence. Interestingly, figural intelligence associations were dependent on sex and intelligence factor; in females, the pallidum volumes were correlated with crystallised figural intelligence (r = 0.372, p = 0.01), whereas in males, the caudate volumes were correlated with fluid figural intelligence (r = 0.507, p = 0.01). Numeric intelligence was correlated with right-lateralised caudate nucleus volumes for both females and males, but only for crystallised intelligence (r = 0.306, p = 0.04 and r = 0.459, p = 0.04, respectively). The associations were not mediated by prefrontal cortical subfield volumes when controlling with partial correlation analyses. Conclusions/Significance The findings of our exploratory analysis indicate that figural and numeric intelligence aspects, but not verbal aspects, are strongly associated with basal ganglia volumes. Unlike numeric intelligence, the type of figural intelligence appears to be related to distinct basal ganglia

  15. The inhibitory microcircuit of the substantia nigra provides feedback gain control of the basal ganglia output.

    PubMed

    Brown, Jennifer; Pan, Wei-Xing; Dudman, Joshua Tate

    2014-05-21

    Dysfunction of the basal ganglia produces severe deficits in the timing, initiation, and vigor of movement. These diverse impairments suggest a control system gone awry. In engineered systems, feedback is critical for control. By contrast, models of the basal ganglia highlight feedforward circuitry and ignore intrinsic feedback circuits. In this study, we show that feedback via axon collaterals of substantia nigra projection neurons control the gain of the basal ganglia output. Through a combination of physiology, optogenetics, anatomy, and circuit mapping, we elaborate a general circuit mechanism for gain control in a microcircuit lacking interneurons. Our data suggest that diverse tonic firing rates, weak unitary connections and a spatially diffuse collateral circuit with distinct topography and kinetics from feedforward input is sufficient to implement divisive feedback inhibition. The importance of feedback for engineered systems implies that the intranigral microcircuit, despite its absence from canonical models, could be essential to basal ganglia function. DOI: http://dx.doi.org/10.7554/eLife.02397.001. Copyright © 2014, Brown et al.

  16. iPhone-Assisted Augmented Reality Localization of Basal Ganglia Hypertensive Hematoma.

    PubMed

    Hou, YuanZheng; Ma, LiChao; Zhu, RuYuan; Chen, XiaoLei

    2016-10-01

    A low-cost, time-efficient technique that could localize hypertensive hematomas in the basal ganglia would be beneficial for minimally invasive hematoma evacuation surgery. We used an iPhone to achieve this goal and evaluated its accuracy and feasibility. We located basal ganglia hematomas in 26 patients and depicted the boundaries of the hematomas on the skin. To verify the accuracy of the drawn boundaries, computed tomography (CT) markers surrounding the depicted boundaries were attached to 10 patients. The deviation between the CT markers and the actual hematoma boundaries was then measured. In the other 16 patients, minimally invasive endoscopic hematoma evacuation surgery was performed according to the depicted hematoma boundary. The deflection angle of the actual trajectory and deviation in the hematoma center were measured according to the preoperative and postoperative CT data. There were 40 CT markers placed on 10 patients. The mean deviation of these markers was 3.1 mm ± 2.4. In the 16 patients who received surgery, the deflection angle of the actual trajectory was 4.3° ± 2.1. The deviation in the hematoma center was 5.2 mm ± 2.6. This new method can locate basal ganglia hematomas with a sufficient level of accuracy and is helpful for minimally invasive endoscopic hematoma evacuation surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Remodeling of Dendritic Spines in the Avian Vocal Motor Cortex Following Deafening Depends on the Basal Ganglia Circuit.

    PubMed

    Zhou, Xin; Fu, Xin; Lin, Chun; Zhou, Xiaojuan; Liu, Jin; Wang, Li; Zhang, Xinwen; Zuo, Mingxue; Fan, Xiaolong; Li, Dapeng; Sun, Yingyu

    2017-05-01

    Deafening elicits a deterioration of learned vocalization, in both humans and songbirds. In songbirds, learned vocal plasticity has been shown to depend on the basal ganglia-cortical circuit, but the underlying cellular basis remains to be clarified. Using confocal imaging and electron microscopy, we examined the effect of deafening on dendritic spines in avian vocal motor cortex, the robust nucleus of the arcopallium (RA), and investigated the role of the basal ganglia circuit in motor cortex plasticity. We found rapid structural changes to RA dendritic spines in response to hearing loss, accompanied by learned song degradation. In particular, the morphological characters of RA spine synaptic contacts between 2 major pathways were altered differently. However, experimental disruption of the basal ganglia circuit, through lesions in song-specialized basal ganglia nucleus Area X, largely prevented both the observed changes to RA dendritic spines and the song deterioration after hearing loss. Our results provide cellular evidence to highlight a key role of the basal ganglia circuit in the motor cortical plasticity that underlies learned vocal plasticity. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Correlation transfer from basal ganglia to thalamus in Parkinson's disease

    PubMed Central

    Pamela, Reitsma; Brent, Doiron; Jonathan, Rubin

    2011-01-01

    Spike trains from neurons in the basal ganglia of parkinsonian primates show increased pairwise correlations, oscillatory activity, and burst rate compared to those from neurons recorded during normal brain activity. However, it is not known how these changes affect the behavior of downstream thalamic neurons. To understand how patterns of basal ganglia population activity may affect thalamic spike statistics, we study pairs of model thalamocortical (TC) relay neurons receiving correlated inhibitory input from the internal segment of the globus pallidus (GPi), a primary output nucleus of the basal ganglia. We observe that the strength of correlations of TC neuron spike trains increases with the GPi correlation level, and bursty firing patterns such as those seen in the parkinsonian GPi allow for stronger transfer of correlations than do firing patterns found under normal conditions. We also show that the T-current in the TC neurons does not significantly affect correlation transfer, despite its pronounced effects on spiking. Oscillatory firing patterns in GPi are shown to affect the timescale at which correlations are best transferred through the system. To explain this last result, we analytically compute the spike count correlation coefficient for oscillatory cases in a reduced point process model. Our analysis indicates that the dependence of the timescale of correlation transfer is robust to different levels of input spike and rate correlations and arises due to differences in instantaneous spike correlations, even when the long timescale rhythmic modulations of neurons are identical. Overall, these results show that parkinsonian firing patterns in GPi do affect the transfer of correlations to the thalamus. PMID:22355287

  19. Ketamine-Induced Oscillations in the Motor Circuit of the Rat Basal Ganglia

    PubMed Central

    Alegre, Manuel; Pérez-Alcázar, Marta; Iriarte, Jorge; Artieda, Julio

    2011-01-01

    Oscillatory activity can be widely recorded in the cortex and basal ganglia. This activity may play a role not only in the physiology of movement, perception and cognition, but also in the pathophysiology of psychiatric and neurological diseases like schizophrenia or Parkinson's disease. Ketamine administration has been shown to cause an increase in gamma activity in cortical and subcortical structures, and an increase in 150 Hz oscillations in the nucleus accumbens in healthy rats, together with hyperlocomotion. We recorded local field potentials from motor cortex, caudate-putamen (CPU), substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN) in 20 awake rats before and after the administration of ketamine at three different subanesthetic doses (10, 25 and 50 mg/Kg), and saline as control condition. Motor behavior was semiautomatically quantified by custom-made software specifically developed for this setting. Ketamine induced coherent oscillations in low gamma (50 Hz), high gamma (80 Hz) and high frequency (HFO, 150 Hz) bands, with different behavior in the four structures studied. While oscillatory activity at these three peaks was widespread across all structures, interactions showed a different pattern for each frequency band. Imaginary coherence at 150 Hz was maximum between motor cortex and the different basal ganglia nuclei, while low gamma coherence connected motor cortex with CPU and high gamma coherence was more constrained to the basal ganglia nuclei. Power at three bands correlated with the motor activity of the animal, but only coherence values in the HFO and high gamma range correlated with movement. Interactions in the low gamma band did not show a direct relationship to movement. These results suggest that the motor effects of ketamine administration may be primarily mediated by the induction of coherent widespread high-frequency activity in the motor circuit of the basal ganglia, together with a frequency-specific pattern of

  20. Severity of dysfluency correlates with basal ganglia activity in persistent developmental stuttering.

    PubMed

    Giraud, Anne-Lise; Neumann, Katrin; Bachoud-Levi, Anne-Catherine; von Gudenberg, Alexander W; Euler, Harald A; Lanfermann, Heinrich; Preibisch, Christine

    2008-02-01

    Previous studies suggest that anatomical anomalies [Foundas, A. L., Bollich, A. M., Corey, D. M., Hurley, M., & Heilman, K. M. (2001). Anomalous anatomy of speech-language areas in adults with persistent developmental stuttering. Neurology, 57, 207-215; Foundas, A. L., Corey, D. M., Angeles, V., Bollich, A. M., Crabtree-Hartman, E., & Heilman, K. M. (2003). Atypical cerebral laterality in adults with persistent developmental stuttering. Neurology, 61, 1378-1385; Foundas, A. L., Bollich, A. M., Feldman, J., Corey, D. M., Hurley, M., & Lemen, L. C. et al., (2004). Aberrant auditory processing and atypical planum temporale in developmental stuttering. Neurology, 63, 1640-1646; Jancke, L., Hanggi, J., & Steinmetz, H. (2004). Morphological brain differences between adult stutterers and non-stutterers. BMC Neurology, 4, 23], in particular a reduction of the white matter anisotropy underlying the left sensorimotor cortex [Sommer, M., Koch, M. A., Paulus, W., Weiller, C., & Buchel, C. (2002). Disconnection of speech-relevant brain areas in persistent developmental stuttering. Lancet, 360, 380-383] could be at the origin of persistent developmental stuttering (PDS). Because neural connections between the motor cortex and basal ganglia are implicated in speech motor functions, PDS could also be associated with a dysfunction in basal ganglia activity [Alm, P. (2004). Stuttering and the basal ganglia circuits: a critical review of possible relations. Journal of Communication Disorders, 37, 325-369]. This fMRI study reports a correlation between severity of stuttering and activity in the basal ganglia and shows that this activity is modified by fluency shaping therapy through long-term therapy effects that reflect speech production improvement. A model of dysfunction in stuttering and possible repair modes is proposed that accommodates the data presented here and observations previously made by us and by others.

  1. Computational models of basal-ganglia pathway functions: focus on functional neuroanatomy

    PubMed Central

    Schroll, Henning; Hamker, Fred H.

    2013-01-01

    Over the past 15 years, computational models have had a considerable impact on basal-ganglia research. Most of these models implement multiple distinct basal-ganglia pathways and assume them to fulfill different functions. As there is now a multitude of different models, it has become complex to keep track of their various, sometimes just marginally different assumptions on pathway functions. Moreover, it has become a challenge to oversee to what extent individual assumptions are corroborated or challenged by empirical data. Focusing on computational, but also considering non-computational models, we review influential concepts of pathway functions and show to what extent they are compatible with or contradict each other. Moreover, we outline how empirical evidence favors or challenges specific model assumptions and propose experiments that allow testing assumptions against each other. PMID:24416002

  2. Conditional Routing of Information to the Cortex: A Model of the Basal Ganglia's Role in Cognitive Coordination

    ERIC Educational Resources Information Center

    Stocco, Andrea; Lebiere, Christian; Anderson, John R.

    2010-01-01

    The basal ganglia play a central role in cognition and are involved in such general functions as action selection and reinforcement learning. Here, we present a model exploring the hypothesis that the basal ganglia implement a conditional information-routing system. The system directs the transmission of cortical signals between pairs of regions…

  3. Basal ganglia function, stuttering, sequencing, and repair in adult songbirds.

    PubMed

    Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D

    2014-10-13

    A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations.

  4. Surprise disrupts cognition via a fronto-basal ganglia suppressive mechanism

    PubMed Central

    Wessel, Jan R.; Jenkinson, Ned; Brittain, John-Stuart; Voets, Sarah H. E. M.; Aziz, Tipu Z.; Aron, Adam R.

    2016-01-01

    Surprising events markedly affect behaviour and cognition, yet the underlying mechanism is unclear. Surprise recruits a brain mechanism that globally suppresses motor activity, ostensibly via the subthalamic nucleus (STN) of the basal ganglia. Here, we tested whether this suppressive mechanism extends beyond skeletomotor suppression and also affects cognition (here, verbal working memory, WM). We recorded scalp-EEG (electrophysiology) in healthy participants and STN local field potentials in Parkinson's patients during a task in which surprise disrupted WM. For scalp-EEG, surprising events engage the same independent neural signal component that indexes action stopping in a stop-signal task. Importantly, the degree of this recruitment mediates surprise-related WM decrements. Intracranially, STN activity is also increased post surprise, especially when WM is interrupted. These results suggest that surprise interrupts cognition via the same fronto-basal ganglia mechanism that interrupts action. This motivates a new neural theory of how cognition is interrupted, and how distraction arises after surprising events. PMID:27088156

  5. Basal ganglia function, stuttering, sequencing, and repair in adult songbirds

    PubMed Central

    Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D.

    2014-01-01

    A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations. PMID:25307086

  6. Motor phenotype and magnetic resonance measures of basal ganglia iron levels in Parkinson's disease☆

    PubMed Central

    Bunzeck, Nico; Singh-Curry, Victoria; Eckart, Cindy; Weiskopf, Nikolaus; Perry, Richard J.; Bain, Peter G.; Düzel, Emrah; Husain, Masud

    2013-01-01

    Background In Parkinson's disease the degree of motor impairment can be classified with respect to tremor dominant and akinetic rigid features. While tremor dominance and akinetic rigidity might represent two ends of a continuum rather than discrete entities, it would be important to have non-invasive markers of any biological differences between them in vivo, to assess disease trajectories and response to treatment, as well as providing insights into the underlying mechanisms contributing to heterogeneity within the Parkinson's disease population. Methods Here, we used magnetic resonance imaging to examine whether Parkinson's disease patients exhibit structural changes within the basal ganglia that might relate to motor phenotype. Specifically, we examined volumes of basal ganglia regions, as well as transverse relaxation rate (a putative marker of iron load) and magnetization transfer saturation (considered to index structural integrity) within these regions in 40 individuals. Results We found decreased volume and reduced magnetization transfer within the substantia nigra in Parkinson's disease patients compared to healthy controls. Importantly, there was a positive correlation between tremulous motor phenotype and transverse relaxation rate (reflecting iron load) within the putamen, caudate and thalamus. Conclusions Our findings suggest that akinetic rigid and tremor dominant symptoms of Parkinson's disease might be differentiated on the basis of the transverse relaxation rate within specific basal ganglia structures. Moreover, they suggest that iron load within the basal ganglia makes an important contribution to motor phenotype, a key prognostic indicator of disease progression in Parkinson's disease. PMID:24025315

  7. Biotin and Thiamine Responsive Basal Ganglia Disease--A vital differential diagnosis in infants with severe encephalopathy.

    PubMed

    Ygberg, Sofia; Naess, Karin; Eriksson, Mats; Stranneheim, Henrik; Lesko, Nicole; Barbaro, Michela; Wibom, Rolf; Wang, Chen; Wedell, Anna; Wickström, Ronny

    2016-05-01

    We report two siblings of Swedish origin with infantile Biotin and Thiamine Responsive Basal Ganglia Disease (BTRBG). Initial symptoms were in both cases lethargia, with reduced contact and poor feeding from the age of 5 weeks. Magnetic resonance imaging showed altered signal in the basal ganglia, along with grey and white matter abnormalities. The diagnosis BTRBG was not recognized in the first sibling who died at the age of 8 weeks. The second sibling was started on biotin and thiamine immediately upon development of symptoms, leading to clinical improvement and partial reversion of the magnetic resonance imaging findings. Genetic analysis of the SLC19A3 gene identified two mutations, c.74dupT and c.1403delA, carried in compound heterozygous form in both boys, each inherited from one parent. The first mutation has previously been described in children with BTRBG, and the second mutation is novel. Although the clinical picture in BTRGB is very severe it is also rather unspecific and the diagnosis may be missed. This report highlights the importance of considering biotin and thiamine treatment also in a European infant born to non-consanguineous parents, who presents with symptoms of acute/subacute encephalopathy. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  8. The Basal Ganglia and Adaptive Motor Control

    NASA Astrophysics Data System (ADS)

    Graybiel, Ann M.; Aosaki, Toshihiko; Flaherty, Alice W.; Kimura, Minoru

    1994-09-01

    The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops. Dysfunction in these parallel loops caused by damage to the striatum results in major defects in voluntary movement, exemplified in Parkinson's disease and Huntington's disease. These parallel loops have a distributed modular architecture resembling local expert architectures of computational learning models. During sensorimotor learning, such distributed networks may be coordinated by widely spaced striatal interneurons that acquire response properties on the basis of experienced reward.

  9. Endoscopic Evacuation of Basal Ganglia Hemorrhage via Keyhole Approach Using an Adjustable Cannula in Comparison with Craniotomy

    PubMed Central

    Zhang, Heng-Zhu; Li, Yu-Ping; Yan, Zheng-cun; Wang, Xing-dong; She, Lei; Wang, Xiao-dong; Dong, Lun

    2014-01-01

    Neuroendoscopic (NE) surgery as a minimal invasive treatment for basal ganglia hemorrhage is a promising approach. The present study aims to evaluate the efficacy and safety of NE approach using an adjustable cannula to treat basal ganglia hemorrhage. In this study, we analysed the clinical and radiographic outcomes between NE group (21 cases) and craniotomy group (30 cases). The results indicated that NE surgery might be an effective and safe approach for basal ganglia haemorrhage, and it is also suggested that NE approach may improve good functional recovery. However, NE approach only suits the selected patient, and the usefulness of NE approach needs further randomized controlled trials (RCTs) to evaluate. PMID:24949476

  10. Effect of basal ganglia calcification on its glucose metabolism and dopaminergic function in idiopathic hypoparathyroidism.

    PubMed

    Modi, Sagar; Arora, Geetanjali; Bal, Chandra Shekhar; Sreenivas, Vishnubhatla; Kailash, Suparna; Sagar, Rajesh; Goswami, Ravinder

    2015-10-01

    The functional significance of basal ganglia calcification (BGC) in idiopathic hypoparathyroidism (IH) is not clear. To assess the effect of BGC on glucose metabolism and dopaminergic function in IH. (18) F-FDG and (99m) Tc-TRODAT-1 nuclear imaging were performed in 35 IH patients with (n = 26) and without (n = 9) BGC. Controls were subjects without hypoparathyroidism or BGC (nine for (18) F-FDG and 12 for (99m) Tc-TRODAT-1). Relationship of the glucose metabolism and dopaminergic function was assessed with the neuropsychological and biochemical abnormalities. (18) F-FDG uptake in IH patients with calcification at caudate and striatum was less than that of IH patients without calcification (1·06 ± 0·13 vs 1·24 ± 0·09, P = <0·0001 and 1·06 ± 0·09 vs 1·14 ± 0·08, P = 0·03, respectively). (18) F-FDG uptake did not correlate with neuropsychological dysfunctions. (18) F-FDG uptake in IH without BGC was significantly lower than that of controls. The mean (99m) Tc-TRODAT-1 uptake at basal ganglia was comparable between IH with and without BGC and between IH without BGC and controls. Serum calcium-phosphorus ratio maintained by the patients correlated with (18) F-FDG uptake at striatum (r = 0·57, P = 0·001). For every 0·1 unit reduction in calcium-phosphorus ratio, (18) F-FDG uptake decreased by 2·5 ± 0·68% (P = 0·001). BGC was associated with modest reduction (15%) in (18) F-FDG uptake at basal ganglia in IH but did not affect dopaminergic function. (18) F-FDG uptake did not correlate with neuropsychological dysfunctions. Interestingly, chronic hypocalcaemia-hyperphosphataemia also contributed to reduction in (18) F-FDG uptake which was independent of BGC. © 2014 John Wiley & Sons Ltd.

  11. Mouse Models of Neurodevelopmental Disease of the Basal Ganglia and Associated Circuits

    PubMed Central

    Pappas, Samuel S.; Leventhal, Daniel K.; Albin, Roger L.; Dauer, William T.

    2014-01-01

    This chapter focuses on neurodevelopmental diseases that are tightly linked to abnormal function of the striatum and connected structures. We begin with an overview of three representative diseases in which striatal dysfunction plays a key role—Tourette syndrome and obsessive-compulsive disorder, Rett's syndrome, and primary dystonia. These diseases highlight distinct etiologies that disrupt striatal integrity and function during development, and showcase the varied clinical manifestations of striatal dysfunction. We then review striatal organization and function, including evidence for striatal roles in online motor control/action selection, reinforcement learning, habit formation, and action sequencing. A key barrier to progress has been the relative lack of animal models of these diseases, though recently there has been considerable progress. We review these efforts, including their relative merits providing insight into disease pathogenesis, disease symptomatology, and basal ganglia function. PMID:24947237

  12. T2-weighted high-intensity signals in the basal ganglia as an interesting image finding in Unverricht-Lundborg disease.

    PubMed

    Korja, Miikka; Ferlazzo, Edoardo; Soilu-Hänninen, Merja; Magaudda, Adriana; Marttila, Reijo; Genton, Pierre; Parkkola, Riitta

    2010-01-01

    We conducted a search for white matter changes (WMCs) in 13 Unverricht-Lundborg disease patients and compared the prevalence of WMCs in these patients to age-matched long-term epileptics and healthy controls. ULD patients had significantly more T2-weighted high-intensity signals on MRI than control subjects, due to the increased prevalence of these signals in the basal ganglia. Interestingly, ULD patients with the basal ganglia changes were overweight. Basal ganglia T2-weighted high-intensity signals are novel findings in ULD. 2009 Elsevier B.V. All rights reserved.

  13. Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output.

    PubMed

    Humphries, Mark D; Gurney, Kevin

    2012-07-01

    Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contributor to the effectiveness of STN DBS. We used our computational model of the complete basal ganglia circuit to show how such a mixture of responses in basal ganglia output naturally arises from the network effects of STN DBS. We replicated the diversification of responses recorded in a primate STN DBS study to show that the model's predicted mixture of responses is consistent with therapeutic STN DBS. We then showed how this 'mixture of response' perspective suggests new ideas for DBS mechanisms: first, that the therapeutic frequency of STN DBS is above 100 Hz because the diversification of responses exhibits a step change above this frequency; and second, that optogenetic models of direct STN stimulation during DBS have proven therapeutically ineffective because they do not replicate the mixture of basal ganglia output responses evoked by electrical DBS. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  14. SLC20A2 DEFICIENCY IN MICE LEADS TO ELEVATED PHOSPHATE LEVELS IN CEREBROSPINAL FLUID AND GLYMPHATIC PATHWAY-ASSOCIATED ARTERIOLAR CALCIFICATION, AND RECAPITULATES HUMAN IDIOPATHIC BASAL GANGLIA CALCIFICATION

    PubMed Central

    Wallingford, MC; Chia, J; Leaf, EM; Borgeia, S; Chavkin, NW; Sawangmake, C; Marro, K; Cox, TC; Speer, MY; Giachelli, CM

    2016-01-01

    Idiopathic basal ganglia calcification is a brain calcification disorder that has been genetically linked to autosomal dominant mutations in the sodium-dependent phosphate co-transporter, SLC20A2. The mechanisms whereby deficiency of Slc20a2 leads to basal ganglion calcification are unknown. In the mouse brain, we found that Slc20a2 was expressed in tissues that produce and/or regulate cerebrospinal fluid, including choroid plexus, ependyma and arteriolar smooth muscle cells. Haploinsufficient Slc20a2 +/− mice developed age-dependent basal ganglia calcification that formed in glymphatic pathway-associated arterioles. Slc20a2 deficiency uncovered phosphate homeostasis dysregulation characterized by abnormally high cerebrospinal fluid phosphate levels and hydrocephalus, in addition to basal ganglia calcification. Slc20a2 siRNA knockdown in smooth muscle cells revealed increased susceptibility to high phosphate-induced calcification. These data suggested that loss of Slc20a2 led to dysregulated phosphate homeostasis and enhanced susceptibility of arteriolar smooth muscle cells to elevated phosphate-induced calcification. Together, dysregulated cerebrospinal fluid phosphate and enhanced smooth muscle cell susceptibility may predispose to glymphatic pathway-associated arteriolar calcification. PMID:26822507

  15. Activity propagation in an avian basal ganglia-thalamo-cortical circuit essential for vocal learning

    PubMed Central

    Kojima, Satoshi; Doupe, Allison J.

    2009-01-01

    In mammalian basal ganglia-thalamo-cortical circuits, GABAergic pallidal neurons are thought to ‘gate’ or modulate excitation in thalamus with their strong inhibitory inputs, and thus signal to cortex by pausing and permitting thalamic neurons to fire in response to excitatory drive. In contrast, in a homologous circuit specialized for vocal learning in songbirds, evidence suggests that pallidal neurons signal by eliciting postinhibitory rebound spikes in thalamus, which could occur even without any excitatory drive to thalamic neurons. To test whether songbird pallidal neurons can also communicate with thalamus by gating excitatory drive, as well as by postinhibitory rebound, we examined the activity of thalamic relay neurons in response to acute inactivation of the basal ganglia structure Area X; Area X contains the pallidal neurons that project to thalamus. Although inactivation of Area X should eliminate rebound-mediated spiking in thalamus, this manipulation tonically increases the firing rate of thalamic relay neurons, providing evidence that songbird pallidal neurons can gate tonic thalamic excitatory drive. We also found that the increased thalamic activity was fed forward to its target in the avian equivalent of cortex, which includes neurons that project to the vocal premotor area. These data raise the possibility that basal ganglia circuits can signal to cortex through thalamus both by generating postinhibitory rebound and by gating excitatory drive, and may switch between these modes depending on the statistics of pallidal firing. Moreover, these findings provide insight into the strikingly different disruptive effects of basal ganglia and ‘cortical’ lesions on songbird vocal learning. PMID:19369547

  16. [The early diagnosis of juvenile germinoma originating from the basal ganglia and thalamus].

    PubMed

    Wang, Xian-Ling; Li, Cun-Jiang

    2011-04-01

    To explore the early diagnosis of germinoma originating from the basal ganglia (BG) and thalamus during juveniles. Retrospective analysis was done with the clinical cases of germinomas in BG and thalamus from 2000 to 2009. The symptoms, signs, neuroimaging, cerebrospinal fluid (CSF) findings were analyzed and related literature were reviewed. Eight patents were collected. The main symptoms were hemiplegia, associated with aphasia and/or impaired cognition. Brain CT showed high density and calcification. Abnormal T1 and T2 signal were found in brain MRI frequently associated with ipsilateral hemisphere atrophy. MRS showed increased choline and decreased N-acetylaspartate level. Elevated CSF human chorionic gonadotrophin level were found in two of them. Germinoma in BG and thalamus predominates in a boy. The neuroimaging features are very informative for early diagnosis.

  17. Effect of an 8-week practice of externally triggered speech on basal ganglia activity of stuttering and fluent speakers.

    PubMed

    Toyomura, Akira; Fujii, Tetsunoshin; Kuriki, Shinya

    2015-04-01

    The neural mechanisms underlying stuttering are not well understood. It is known that stuttering appears when persons who stutter speak in a self-paced manner, but speech fluency is temporarily increased when they speak in unison with external trigger such as a metronome. This phenomenon is very similar to the behavioral improvement by external pacing in patients with Parkinson's disease. Recent imaging studies have also suggested that the basal ganglia are involved in the etiology of stuttering. In addition, previous studies have shown that the basal ganglia are involved in self-paced movement. Then, the present study focused on the basal ganglia and explored whether long-term speech-practice using external triggers can induce modification of the basal ganglia activity of stuttering speakers. Our study of functional magnetic resonance imaging revealed that stuttering speakers possessed significantly lower activity in the basal ganglia than fluent speakers before practice, especially when their speech was self-paced. After an 8-week speech practice of externally triggered speech using a metronome, the significant difference in activity between the two groups disappeared. The cerebellar vermis of stuttering speakers showed significantly decreased activity during the self-paced speech in the second compared to the first experiment. The speech fluency and naturalness of the stuttering speakers were also improved. These results suggest that stuttering is associated with defective motor control during self-paced speech, and that the basal ganglia and the cerebellum are involved in an improvement of speech fluency of stuttering by the use of external trigger. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. High frequency stimulation of the entopeduncular nucleus sets the cortico-basal ganglia network to a new functional state in the dystonic hamster.

    PubMed

    Reese, René; Charron, Giselle; Nadjar, Agnès; Aubert, Incarnation; Thiolat, Marie-Laure; Hamann, Melanie; Richter, Angelika; Bezard, Erwan; Meissner, Wassilios G

    2009-09-01

    High frequency stimulation (HFS) of the internal pallidum is effective for the treatment of dystonia. Only few studies have investigated the effects of stimulation on the activity of the cortex-basal ganglia network. We here assess within this network the effect of entopeduncular nucleus (EP) HFS on the expression of c-Fos and cytochrome oxidase subunit I (COI) in the dt(sz)-hamster, a well-characterized model of paroxysmal dystonia. In dt(sz)-hamsters, we identified abnormal activity in motor cortex, basal ganglia and thalamus. These structures have already been linked to the pathophysiology of human dystonia. EP-HFS (i) increased striatal c-Fos expression in controls and dystonic hamsters and (ii) reduced thalamic c-Fos expression in dt(sz)-hamsters. EP-HFS had no effect on COI expression. The present results suggest that EP-HFS induces a new network activity state which may improve information processing and finally reduces the severity of dystonic attacks in dt(sz)-hamsters.

  19. Left and right basal ganglia and frontal activity during language generation: contributions to lexical, semantic, and phonological processes.

    PubMed

    Crosson, Bruce; Benefield, Hope; Cato, M Allison; Sadek, Joseph R; Moore, Anna Bacon; Wierenga, Christina E; Gopinath, Kaundinya; Soltysik, David; Bauer, Russell M; Auerbach, Edward J; Gökçay, Didem; Leonard, Christiana M; Briggs, Richard W

    2003-11-01

    fMRI was used to determine the frontal, basal ganglia, and thalamic structures engaged by three facets of language generation: lexical status of generated items, the use of semantic vs. phonological information during language generation, and rate of generation. During fMRI, 21 neurologically normal subjects performed four tasks: generation of nonsense syllables given beginning and ending consonant blends, generation of words given a rhyming word, generation of words given a semantic category at a fast rate (matched to the rate of nonsense syllable generation), and generation of words given a semantic category at a slow rate (matched to the rate of generating of rhyming words). Components of a left pre-SMA-dorsal caudate nucleus-ventral anterior thalamic loop were active during word generation from rhyming or category cues but not during nonsense syllable generation. Findings indicate that this loop is involved in retrieving words from pre-existing lexical stores. Relatively diffuse activity in the right basal ganglia (caudate nucleus and putamen) also was found during word-generation tasks but not during nonsense syllable generation. Given the relative absence of right frontal activity during the word generation tasks, we suggest that the right basal ganglia activity serves to suppress right frontal activity, preventing right frontal structures from interfering with language production. Current findings establish roles for the left and the right basal ganglia in word generation. Hypotheses are discussed for future research to help refine our understanding of basal ganglia functions in language generation.

  20. Simulation of cortico-basal ganglia oscillations and their suppression by closed loop deep brain stimulation.

    PubMed

    Grant, Peadar F; Lowery, Madeleine M

    2013-07-01

    A new model of deep brain stimulation (DBS) is presented that integrates volume conduction effects with a neural model of pathological beta-band oscillations in the cortico-basal ganglia network. The model is used to test the clinical hypothesis that closed-loop control of the amplitude of DBS may be possible, based on the average rectified value of beta-band oscillations in the local field potential. Simulation of closed-loop high-frequency DBS was shown to yield energy savings, with the magnitude of the energy saved dependent on the strength of coupling between the subthalamic nucleus and the remainder of the cortico-basal ganglia network. When closed-loop DBS was applied to a strongly coupled cortico-basal ganglia network, the stimulation energy delivered over a 480 s period was reduced by up to 42%. Greater energy reductions were observed for weakly coupled networks, as the stimulation amplitude reduced to zero once the initial desynchronization had occurred. The results provide support for the application of closed-loop high-frequency DBS based on electrophysiological biomarkers.

  1. BAC to degeneration bacterial artificial chromosome (BAC)-mediated transgenesis for modeling basal ganglia neurodegenerative disorders.

    PubMed

    Lu, Xiao-Hong

    2009-01-01

    Basal ganglia neurodegenerative disorders, such as Parkinson's disease (PD) and Huntington's disease (HD), are characterized by not only spectrum of motor deficits, ranging form hypokinesia to hyperkinesia, but also emotional, cognitive, and psychiatric manifestations. The symptoms and pathogenic mechanism of these disorders should be viewed as dysfunctions of specific cortico-subcortical neurocircuits. Transgenic approaches using large genomic inserts, such as bacterial artificial chromosome (BAC)-mediated transgenesis, due to its capacity to propagate large-size genomic DNA and faithful production of endogenous-like gene expression pattern/lever, have provided an ideal basis for the generation of transgenic mice as model for basal ganglia neurodegenerative disorders, as well as the functional and structural analysis of neurocircuits. In this chapter, the basic concepts and practical approaches about application of BAC transgenic system are introduced. Existent major BAC transgenic mouse models for PD and HD are evaluated according to their construct, face, and predicative validity. Finally, considerations, possible solutions, and future perspectives of using BAC transgenic approach to study basal ganglia neurodegenerative disorders are discussed.

  2. A neural mass model of basal ganglia nuclei simulates pathological beta rhythm in Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Liu, Fei; Wang, Jiang; Liu, Chen; Li, Huiyan; Deng, Bin; Fietkiewicz, Chris; Loparo, Kenneth A.

    2016-12-01

    An increase in beta oscillations within the basal ganglia nuclei has been shown to be associated with movement disorder, such as Parkinson's disease. The motor cortex and an excitatory-inhibitory neuronal network composed of the subthalamic nucleus (STN) and the external globus pallidus (GPe) are thought to play an important role in the generation of these oscillations. In this paper, we propose a neuron mass model of the basal ganglia on the population level that reproduces the Parkinsonian oscillations in a reciprocal excitatory-inhibitory network. Moreover, it is shown that the generation and frequency of these pathological beta oscillations are varied by the coupling strength and the intrinsic characteristics of the basal ganglia. Simulation results reveal that increase of the coupling strength induces the generation of the beta oscillation, as well as enhances the oscillation frequency. However, for the intrinsic properties of each nucleus in the excitatory-inhibitory network, the STN primarily influences the generation of the beta oscillation while the GPe mainly determines its frequency. Interestingly, describing function analysis applied on this model theoretically explains the mechanism of pathological beta oscillations.

  3. Optogenetic Activation of the Sensorimotor Cortex Reveals "Local Inhibitory and Global Excitatory" Inputs to the Basal Ganglia.

    PubMed

    Ozaki, Mitsunori; Sano, Hiromi; Sato, Shigeki; Ogura, Mitsuhiro; Mushiake, Hajime; Chiken, Satomi; Nakao, Naoyuki; Nambu, Atsushi

    2017-12-01

    To understand how information from different cortical areas is integrated and processed through the cortico-basal ganglia pathways, we used optogenetics to systematically stimulate the sensorimotor cortex and examined basal ganglia activity. We utilized Thy1-ChR2-YFP transgenic mice, in which channelrhodopsin 2 is robustly expressed in layer V pyramidal neurons. We applied light spots to the sensorimotor cortex in a grid pattern and examined neuronal responses in the globus pallidus (GP) and entopeduncular nucleus (EPN), which are the relay and output nuclei of the basal ganglia, respectively. Light stimulation typically induced a triphasic response composed of early excitation, inhibition, and late excitation in GP/EPN neurons. Other response patterns lacking 1 or 2 of the components were also observed. The distribution of the cortical sites whose stimulation induced a triphasic response was confined, whereas stimulation of the large surrounding areas induced early and late excitation without inhibition. Our results suggest that cortical inputs to the GP/EPN are organized in a "local inhibitory and global excitatory" manner. Such organization seems to be the neuronal basis for information processing through the cortico-basal ganglia pathways, that is, releasing and terminating necessary information at an appropriate timing, while simultaneously suppressing other unnecessary information. © The Author 2017. Published by Oxford University Press.

  4. Effects of Focal Basal Ganglia Lesions on Timing and Force Control

    ERIC Educational Resources Information Center

    Aparicio, P.; Diedrichsen, J.; Ivry, R.B.

    2005-01-01

    Studies of basal ganglia dysfunction in humans have generally involved patients with degenerative disorders, notably Parkinson's disease. In many instances, the performance of these patients is compared to that of patients with focal lesions of other brain structures such as the cerebellum. In the present report, we studied the performance of…

  5. Role of Basal Ganglia Circuits in Resisting Interference by Distracters: A swLORETA Study

    PubMed Central

    Bocquillon, Perrine; Bourriez, Jean-Louis; Palmero-Soler, Ernesto; Destée, Alain; Defebvre, Luc; Derambure, Philippe; Dujardin, Kathy

    2012-01-01

    Background The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. Both mechanisms rely on a dorsal frontoparietal network, while focalization additionally involves a ventral frontoparietal network. The role of subcortical structures in attention is less clear, despite the fact that the striatum interacts significantly with the frontal cortex via frontostriatal loops. One means of investigating the basal ganglia's contributions to attention is to examine the features of P300 components (i.e. amplitude, latency, and generators) in patients with basal ganglia damage (such as in Parkinson's disease (PD), in which attention is often impaired). Three-stimulus oddball paradigms can be used to study distracter-elicited and target-elicited P300 subcomponents. Methodology/Principal Findings In order to compare distracter- and target-elicited P300 components, high-density (128-channel) electroencephalograms were recorded during a three-stimulus visual oddball paradigm in 15 patients with early PD and 15 matched healthy controls. For each subject, the P300 sources were localized using standardized weighted low-resolution electromagnetic tomography (swLORETA). Comparative analyses (one-sample and two-sample t-tests) were performed using SPM5® software. The swLORETA analyses showed that PD patients displayed fewer dorsolateral prefrontal (DLPF) distracter-P300 generators but no significant differences in target-elicited P300 sources; this suggests dysfunction of the DLPF cortex when the executive frontostriatal loop is disrupted by basal ganglia damage. Conclusions/Significance Our results suggest that the cortical attention frontoparietal networks (mainly the dorsal one) are modulated by the basal ganglia. Disruption of this network in PD impairs resistance to distracters, which results in attention disorders. PMID:22470542

  6. Mean-field modeling of the basal ganglia-thalamocortical system. II Dynamics of parkinsonian oscillations.

    PubMed

    van Albada, S J; Gray, R T; Drysdale, P M; Robinson, P A

    2009-04-21

    Neuronal correlates of Parkinson's disease (PD) include a shift to lower frequencies in the electroencephalogram (EEG) and enhanced synchronized oscillations at 3-7 and 7-30 Hz in the basal ganglia, thalamus, and cortex. This study describes the dynamics of a recent physiologically based mean-field model of the basal ganglia-thalamocortical system, and shows how it accounts for many key electrophysiological correlates of PD. Its detailed functional connectivity comprises partially segregated direct and indirect pathways through two populations of striatal neurons, a hyperdirect pathway involving a corticosubthalamic projection, thalamostriatal feedback, and local inhibition in striatum and external pallidum (GPe). In a companion paper, realistic steady-state firing rates were obtained for the healthy state, and after dopamine loss modeled by weaker direct and stronger indirect pathways, reduced intrapallidal inhibition, lower firing thresholds of the GPe and subthalamic nucleus (STN), a stronger projection from striatum to GPe, and weaker cortical interactions. Here it is shown that oscillations around 5 and 20 Hz can arise with a strong indirect pathway, which also causes increased synchronization throughout the basal ganglia. Furthermore, increased theta power with progressive nigrostriatal degeneration is correlated with reduced alpha power and peak frequency, in agreement with empirical results. Unlike the hyperdirect pathway, the indirect pathway sustains oscillations with phase relationships that coincide with those found experimentally. Alterations in the responses of basal ganglia to transient stimuli accord with experimental observations. Reduced cortical gains due to both nigrostriatal and mesocortical dopamine loss lead to slower changes in cortical activity and may be related to bradykinesia. Finally, increased EEG power found in some studies may be partly explained by a lower effective GPe firing threshold, reduced GPe-GPe inhibition, and/or weaker

  7. Vocal babbling in songbirds requires the basal ganglia-recipient motor thalamus but not the basal ganglia

    PubMed Central

    Goldberg, Jesse H.

    2011-01-01

    Young songbirds produce vocal “babbling,” and the variability of their songs is thought to underlie a process of trial-and-error vocal learning. It is known that this exploratory variability requires the “cortical” component of a basal ganglia (BG) thalamocortical loop, but less understood is the role of the BG and thalamic components in this behavior. We found that large bilateral lesions to the songbird BG homolog Area X had little or no effect on song variability during vocal babbling. In contrast, lesions to the BG-recipient thalamic nucleus DLM (medial portion of the dorsolateral thalamus) largely abolished normal vocal babbling in young birds and caused a dramatic increase in song stereotypy. These findings support the idea that the motor thalamus plays a key role in the expression of exploratory juvenile behaviors during learning. PMID:21430276

  8. Crossed cerebellar and uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease

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

    Akiyama, H.; Harrop, R.; McGeer, P.L.

    1989-04-01

    We detected crossed cerebellar as well as uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease by positron emission tomography (PET) using /sup 18/F-fluorodeoxyglucose. We studied a series of 26 consecutive, clinically diagnosed Alzheimer cases, including 6 proven by later autopsy, and compared them with 9 age-matched controls. We calculated asymmetry indices (AIs) of cerebral metabolic rate for matched left-right regions of interest (ROIs) and determined the extent of diaschisis by correlative analyses. For the Alzheimer group, we found cerebellar AIs correlated negatively, and thalamic AIs positively, with those of the cerebral hemisphere and frontal, temporal, parietal, and angular cortices,more » while basal ganglia AIs correlated positively with frontal cortical AIs. The only significant correlation of AIs for normal subjects was between the thalamus and cerebral hemisphere. These data indicate that PET is a sensitive technique for detecting diaschisis.« less

  9. Hyporesponsive reward anticipation in the basal ganglia following severe institutional deprivation early in life.

    PubMed

    Mehta, Mitul A; Gore-Langton, Emma; Golembo, Nicole; Colvert, Emma; Williams, Steven C R; Sonuga-Barke, Edmund

    2010-10-01

    Severe deprivation in the first few years of life is associated with multiple difficulties in cognition and behavior. However, the brain basis for these difficulties is poorly understood. Structural and functional neuroimaging studies have implicated limbic system structures as dysfunctional, and one functional imaging study in a heterogeneous group of maltreated individuals has confirmed the presence of abnormalities in the basal ganglia. Based on these studies and known dopaminergic abnormalities from studies in experimental animals using social isolation, we used a task of monetary reward anticipation to examine the functional integrity of brain regions previously shown to be implicated in reward processing. Our sample included a group of adolescents (n = 12) who had experienced global deprivation early in their lives in Romania prior to adoption into UK families. In contrast to a nonadopted comparison group (n = 11), the adoptees did not recruit the striatum during reward anticipation despite comparable performance accuracy and latency. These results show, for the first time, an association between early institutional deprivation and brain reward systems in humans and highlight potential neural vulnerabilities resulting from such exposures.

  10. Cannabinoid–dopamine interactions in the physiology and physiopathology of the basal ganglia

    PubMed Central

    García, Concepción; Palomo‐Garo, Cristina; Gómez‐Gálvez, Yolanda

    2015-01-01

    Endocannabinoids and their receptors play a modulatory role in the control of dopamine transmission in the basal ganglia. However, this influence is generally indirect and exerted through the modulation of GABA and glutamate inputs received by nigrostriatal dopaminergic neurons, which lack cannabinoid CB1 receptors although they may produce endocannabinoids. Additional evidence suggests that CB2 receptors may be located in nigrostriatal dopaminergic neurons, and that certain eicosanoid‐related cannabinoids may directly activate TRPV1 receptors, which have been found in nigrostriatal dopaminergic neurons, thus allowing in both cases a direct regulation of dopamine transmission by specific cannabinoids. In addition, CB1 receptors form heteromers with dopaminergic receptors which provide another pathway to direct interactions between both systems, in this case at the postsynaptic level. Through these direct mechanisms or through indirect mechanisms involving GABA or glutamate neurons, cannabinoids may interact with dopaminergic transmission in the basal ganglia and this is likely to have important effects on dopamine‐related functions in these structures (i.e. control of movement) and, particularly, on different pathologies affecting these processes, in particular, Parkinson's disease, but also dyskinesia, dystonia and other pathological conditions. The present review will address the current literature supporting these cannabinoid–dopamine interactions at the basal ganglia, with emphasis on aspects dealing with the physiopathological consequences of these interactions. Linked Articles This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc PMID:26059564

  11. Parkinson's disease and other basal ganglia or movement disorders in a large nationwide cohort of Swedish welders

    PubMed Central

    Fored, C M; Fryzek, J P; Brandt, L; Nise, G; Sjögren, B; McLaughlin, J K; Blot, W J; Ekbom, A

    2006-01-01

    Introduction Although it has been hypothesised that metal welding and flame cutting are associated with an increased risk for Parkinson's disease due to manganese released in the welding fume, few rigorous cohort studies have evaluated this risk. Methods The authors examined the relation between employment as a welder and all basal ganglia and movement disorders (ICD‐10, G20–26) in Sweden using nationwide and population based registers. All men recorded as welders or flame cutters (n = 49 488) in the 1960 or 1970 Swedish National Census were identified and their rates of specific basal ganglia and movement disorders between 1964 and 2003 were compared with those in an age and geographical area matched general population comparison cohort of gainfully employed men (n = 489 572). Results The overall rate for basal ganglia and movement disorders combined was similar for the welders and flame cutters compared with the general population (adjusted rate ratio (aRR) = 0.91 (95% CI 0.81 to 1.01). Similarly, the rate ratio for PD was 0.89 (95% CI 0.79 to 0.99). Adjusted rate ratios for other individual basal ganglia and movement disorders were also not significantly increased or decreased. Further analyses of Parkinson's disease by attained age, time period of follow up, geographical area of residency, and educational level revealed no significant differences between the welders and the general population. Rates for Parkinson's disease among welders in shipyards, where exposures to welding fumes are higher, were also similar to the general population (aRR = 0.95; 95% CI 0.70 to 1.28). Conclusion This nationwide record linkage study offers no support for a relation between welding and Parkinson's disease or any other specific basal ganglia and movement disorders. PMID:16421393

  12. Computational modeling of stuttering caused by impairments in a basal ganglia thalamo-cortical circuit involved in syllable selection and initiation

    PubMed Central

    Civier, Oren; Bullock, Daniel; Max, Ludo; Guenther, Frank H.

    2013-01-01

    A typical white-matter integrity and elevated dopamine levels have been reported for individuals who stutter. We investigated how such abnormalities may lead to speech dysfluencies due to their effects on a syllable-sequencing circuit that consists of basal ganglia (BG), thalamus, and left ventral premotor cortex (vPMC). “Neurally impaired” versions of the neurocomputational speech production model GODIVA were utilized to test two hypotheses: (1) that white-matter abnormalities disturb the circuit via corticostriatal projections carrying copies of executed motor commands, and (2) that dopaminergic abnormalities disturb the circuit via the striatum. Simulation results support both hypotheses: in both scenarios, the neural abnormalities delay readout of the next syllable’s motor program, leading to dysfluency. The results also account for brain imaging findings during dysfluent speech. It is concluded that each of the two abnormality types can cause stuttering moments, probably by affecting the same BG-thalamus-vPMC circuit. PMID:23872286

  13. Tractographical model of the cortico-basal ganglia and corticothalamic connections: Improving Our Understanding of Deep Brain Stimulation.

    PubMed

    Avecillas-Chasin, Josué M; Rascón-Ramírez, Fernando; Barcia, Juan A

    2016-05-01

    The cortico-basal ganglia and corticothalamic projections have been extensively studied in the context of neurological and psychiatric disorders. Deep brain stimulation (DBS) is known to modulate many of these pathways to produce the desired clinical effect. The aim of this work is to describe the anatomy of the main circuits of the basal ganglia using tractography in a surgical planning station. We used imaging studies of 20 patients who underwent DBS for movement and psychiatric disorders. We segmented the putamen, caudate nucleus (CN), thalamus, and subthalamic nucleus (STN), and we also segmented the cortical areas connected with these subcortical areas. We used tractography to define the subdivisions of the basal ganglia and thalamus through the generation of fibers from the cortical areas to the subcortical structures. We were able to generate the corticostriatal and corticothalamic connections involved in the motor, associative and limbic circuits. Furthermore, we were able to reconstruct the hyperdirect pathway through the corticosubthalamic connections and we found subregions in the STN. Finally, we reconstructed the cortico-subcortical connections of the ventral intermediate nucleus, the nucleus accumbens and the CN. We identified a feasible delineation of the basal ganglia and thalamus connections using tractography. These results could be potentially useful in DBS if the parcellations are used as targets during surgery. © 2016 Wiley Periodicals, Inc.

  14. Structural differences in basal ganglia of elite running versus martial arts athletes: a diffusion tensor imaging study.

    PubMed

    Chang, Yu-Kai; Tsai, Jack Han-Chao; Wang, Chun-Chih; Chang, Erik Chihhung

    2015-07-01

    The aim of this study was to use diffusion tensor imaging (DTI) to characterize and compare microscopic differences in white matter integrity in the basal ganglia between elite professional athletes specializing in running and martial arts. Thirty-three young adults with sport-related skills as elite professional runners (n = 11) or elite professional martial artists (n = 11) were recruited and compared with non-athletic and healthy controls (n = 11). All participants underwent health- and skill-related physical fitness assessments. Fractional anisotropy (FA) and mean diffusivity (MD), the primary indices derived from DTI, were computed for five regions of interest in the bilateral basal ganglia, including the caudate nucleus, putamen, globus pallidus internal segment (GPi), globus pallidus external segment (GPe), and subthalamic nucleus. Results revealed that both athletic groups demonstrated better physical fitness indices compared with their control counterparts, with the running group exhibiting the highest cardiovascular fitness and the martial arts group exhibiting the highest muscular endurance and flexibility. With respect to the basal ganglia, both athletic groups showed significantly lower FA and marginally higher MD values in the GPi compared with the healthy control group. These findings suggest that professional sport or motor skill training is associated with changes in white matter integrity in specific regions of the basal ganglia, although these positive changes did not appear to depend on the type of sport-related motor skill being practiced.

  15. Computational Stimulation of the Basal Ganglia Neurons with Cost Effective Delayed Gaussian Waveforms

    PubMed Central

    Daneshzand, Mohammad; Faezipour, Miad; Barkana, Buket D.

    2017-01-01

    Deep brain stimulation (DBS) has compelling results in the desynchronization of the basal ganglia neuronal activities and thus, is used in treating the motor symptoms of Parkinson's disease (PD). Accurate definition of DBS waveform parameters could avert tissue or electrode damage, increase the neuronal activity and reduce energy cost which will prolong the battery life, hence avoiding device replacement surgeries. This study considers the use of a charge balanced Gaussian waveform pattern as a method to disrupt the firing patterns of neuronal cell activity. A computational model was created to simulate ganglia cells and their interactions with thalamic neurons. From the model, we investigated the effects of modified DBS pulse shapes and proposed a delay period between the cathodic and anodic parts of the charge balanced Gaussian waveform to desynchronize the firing patterns of the GPe and GPi cells. The results of the proposed Gaussian waveform with delay outperformed that of rectangular DBS waveforms used in in-vivo experiments. The Gaussian Delay Gaussian (GDG) waveforms achieved lower number of misses in eliciting action potential while having a lower amplitude and shorter length of delay compared to numerous different pulse shapes. The amount of energy consumed in the basal ganglia network due to GDG waveforms was dropped by 22% in comparison with charge balanced Gaussian waveforms without any delay between the cathodic and anodic parts and was also 60% lower than a rectangular charged balanced pulse with a delay between the cathodic and anodic parts of the waveform. Furthermore, by defining a Synchronization Level metric, we observed that the GDG waveform was able to reduce the synchronization of GPi neurons more effectively than any other waveform. The promising results of GDG waveforms in terms of eliciting action potential, desynchronization of the basal ganglia neurons and reduction of energy consumption can potentially enhance the performance of DBS

  16. Computational Stimulation of the Basal Ganglia Neurons with Cost Effective Delayed Gaussian Waveforms.

    PubMed

    Daneshzand, Mohammad; Faezipour, Miad; Barkana, Buket D

    2017-01-01

    Deep brain stimulation (DBS) has compelling results in the desynchronization of the basal ganglia neuronal activities and thus, is used in treating the motor symptoms of Parkinson's disease (PD). Accurate definition of DBS waveform parameters could avert tissue or electrode damage, increase the neuronal activity and reduce energy cost which will prolong the battery life, hence avoiding device replacement surgeries. This study considers the use of a charge balanced Gaussian waveform pattern as a method to disrupt the firing patterns of neuronal cell activity. A computational model was created to simulate ganglia cells and their interactions with thalamic neurons. From the model, we investigated the effects of modified DBS pulse shapes and proposed a delay period between the cathodic and anodic parts of the charge balanced Gaussian waveform to desynchronize the firing patterns of the GPe and GPi cells. The results of the proposed Gaussian waveform with delay outperformed that of rectangular DBS waveforms used in in-vivo experiments. The Gaussian Delay Gaussian (GDG) waveforms achieved lower number of misses in eliciting action potential while having a lower amplitude and shorter length of delay compared to numerous different pulse shapes. The amount of energy consumed in the basal ganglia network due to GDG waveforms was dropped by 22% in comparison with charge balanced Gaussian waveforms without any delay between the cathodic and anodic parts and was also 60% lower than a rectangular charged balanced pulse with a delay between the cathodic and anodic parts of the waveform. Furthermore, by defining a Synchronization Level metric, we observed that the GDG waveform was able to reduce the synchronization of GPi neurons more effectively than any other waveform. The promising results of GDG waveforms in terms of eliciting action potential, desynchronization of the basal ganglia neurons and reduction of energy consumption can potentially enhance the performance of DBS

  17. [Calcifications of basal ganglia and cerebellum in patient with pseudohypoparathyroidism--case report].

    PubMed

    Kalinowska-Nowak, Anna; Garlicki, Aleksander; Bociaga-Jasik, Monika; Sobczyk-Krupiarz, Iwona; Mach, Tomasz

    2002-01-01

    Presented is the case report of symmetrical calcifications of basal ganglia, cerebellum and subcortical white matter of cerebral hemispheres (Fahr's syndrome) in a 34 year old man with pseudohypoparathyroidism. Attention has been put on characteristic features of Fahr's syndrome and differential diagnosis of this rare disease.

  18. The Differential Effects of Thalamus and Basal Ganglia on Facial Emotion Recognition

    ERIC Educational Resources Information Center

    Cheung, Crystal C. Y.; Lee, Tatia M. C.; Yip, James T. H.; King, Kristin E.; Li, Leonard S. W.

    2006-01-01

    This study examined if subcortical stroke was associated with impaired facial emotion recognition. Furthermore, the lateralization of the impairment and the differential profiles of facial emotion recognition deficits with localized thalamic or basal ganglia damage were also studied. Thirty-eight patients with subcortical strokes and 19 matched…

  19. The many worlds hypothesis of dopamine prediction error: implications of a parallel circuit architecture in the basal ganglia.

    PubMed

    Lau, Brian; Monteiro, Tiago; Paton, Joseph J

    2017-10-01

    Computational models of reinforcement learning (RL) strive to produce behavior that maximises reward, and thus allow software or robots to behave adaptively [1]. At the core of RL models is a learned mapping between 'states'-situations or contexts that an agent might encounter in the world-and actions. A wealth of physiological and anatomical data suggests that the basal ganglia (BG) is important for learning these mappings [2,3]. However, the computations performed by specific circuits are unclear. In this brief review, we highlight recent work concerning the anatomy and physiology of BG circuits that suggest refinements in our understanding of computations performed by the basal ganglia. We focus on one important component of basal ganglia circuitry, midbrain dopamine neurons, drawing attention to data that has been cast as supporting or departing from the RL framework that has inspired experiments in basal ganglia research over the past two decades. We suggest that the parallel circuit architecture of the BG might be expected to produce variability in the response properties of different dopamine neurons, and that variability in response profile may not reflect variable functions, but rather different arguments that serve as inputs to a common function: the computation of prediction error. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. The role of the basal ganglia in learning and memory: insight from Parkinson's disease.

    PubMed

    Foerde, Karin; Shohamy, Daphna

    2011-11-01

    It has long been known that memory is not a single process. Rather, there are different kinds of memory that are supported by distinct neural systems. This idea stemmed from early findings of dissociable patterns of memory impairments in patients with selective damage to different brain regions. These studies highlighted the role of the basal ganglia in non-declarative memory, such as procedural or habit learning, contrasting it with the known role of the medial temporal lobes in declarative memory. In recent years, major advances across multiple areas of neuroscience have revealed an important role for the basal ganglia in motivation and decision making. These findings have led to new discoveries about the role of the basal ganglia in learning and highlighted the essential role of dopamine in specific forms of learning. Here we review these recent advances with an emphasis on novel discoveries from studies of learning in patients with Parkinson's disease. We discuss how these findings promote the development of current theories away from accounts that emphasize the verbalizability of the contents of memory and towards a focus on the specific computations carried out by distinct brain regions. Finally, we discuss new challenges that arise in the face of accumulating evidence for dynamic and interconnected memory systems that jointly contribute to learning. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. The role of the basal ganglia in learning and memory: Insight from Parkinson's disease

    PubMed Central

    2013-01-01

    It has long been known that memory is not a single process. Rather, there are different kinds of memory that are supported by distinct neural systems. This idea stemmed from early findings of dissociable patterns of memory impairments in patients with selective damage to different brain regions. These studies highlighted the role of the basal ganglia in non-declarative memory, such as procedural or habit learning, contrasting it with the known role of the medial temporal lobes in declarative memory. In recent years, major advances across multiple areas of neuroscience have revealed an important role for the basal ganglia in motivation and decision making. These findings have led to new discoveries about the role of the basal ganglia in learning and highlighted the essential role of dopamine in specific forms of learning. Here we review these recent advances with an emphasis on novel discoveries from studies of learning in patients with Parkinson's disease. We discuss how these findings promote the development of current theories away from accounts that emphasize the verbalizability of the contents of memory and towards a focus on the specific computations carried out by distinct brain regions. Finally, we discuss new challenges that arise in the face of accumulating evidence for dynamic and interconnected memory systems that jointly contribute to learning. PMID:21945835

  2. Glutamate and GABA receptors and transporters in the basal ganglia: What does their subsynaptic localization reveal about their function?

    PubMed Central

    Galvan, Adriana; Kuwajima, Masaaki; Smith, Yoland

    2006-01-01

    GABA and glutamate, the main transmitters in the basal ganglia, exert their effects through ionotropic and metabotropic receptors. The dynamic activation of these receptors in response to released neurotransmitter depends, among other factors, on their precise localization in relation to corresponding synapses. The use of high resolution quantitative electron microscope immunocytochemical techniques has provided in-depth description of the subcellular and subsynaptic localization of these receptors in the CNS. In this article, we review recent findings on the ultrastructural localization of GABA and glutamate receptors and transporters in the basal ganglia, at synaptic, extrasynaptic and presynaptic sites. The anatomical evidence supports numerous potential locations for receptor-neurotransmitter interactions, and raises important questions regarding mechanisms of activation and function of synaptic versus extrasynaptic receptors in the basal ganglia. PMID:17059868

  3. A biophysical model of the cortex-basal ganglia-thalamus network in the 6-OHDA lesioned rat model of Parkinson's disease.

    PubMed

    Kumaravelu, Karthik; Brocker, David T; Grill, Warren M

    2016-04-01

    Electrical stimulation of sub-cortical brain regions (the basal ganglia), known as deep brain stimulation (DBS), is an effective treatment for Parkinson's disease (PD). Chronic high frequency (HF) DBS in the subthalamic nucleus (STN) or globus pallidus interna (GPi) reduces motor symptoms including bradykinesia and tremor in patients with PD, but the therapeutic mechanisms of DBS are not fully understood. We developed a biophysical network model comprising of the closed loop cortical-basal ganglia-thalamus circuit representing the healthy and parkinsonian rat brain. The network properties of the model were validated by comparing responses evoked in basal ganglia (BG) nuclei by cortical (CTX) stimulation to published experimental results. A key emergent property of the model was generation of low-frequency network oscillations. Consistent with their putative pathological role, low-frequency oscillations in model BG neurons were exaggerated in the parkinsonian state compared to the healthy condition. We used the model to quantify the effectiveness of STN DBS at different frequencies in suppressing low-frequency oscillatory activity in GPi. Frequencies less than 40 Hz were ineffective, low-frequency oscillatory power decreased gradually for frequencies between 50 Hz and 130 Hz, and saturated at frequencies higher than 150 Hz. HF STN DBS suppressed pathological oscillations in GPe/GPi both by exciting and inhibiting the firing in GPe/GPi neurons, and the number of GPe/GPi neurons influenced was greater for HF stimulation than low-frequency stimulation. Similar to the frequency dependent suppression of pathological oscillations, STN DBS also normalized the abnormal GPi spiking activity evoked by CTX stimulation in a frequency dependent fashion with HF being the most effective. Therefore, therapeutic HF STN DBS effectively suppresses pathological activity by influencing the activity of a greater proportion of neurons in the output nucleus of the BG.

  4. Neuroimaging abnormalities in adults with sickle cell anemia

    PubMed Central

    Insel, Philip; Truran, Diana; Vichinsky, Elliot P.; Neumayr, Lynne D.; Armstrong, F.D.; Gold, Jeffrey I.; Kesler, Karen; Brewer, Joseph; Weiner, Michael W.

    2014-01-01

    Objective: This study was conducted to determine the relationship of frontal lobe cortical thickness and basal ganglia volumes to measures of cognition in adults with sickle cell anemia (SCA). Methods: Participants included 120 adults with SCA with no history of neurologic dysfunction and 33 healthy controls (HCs). Participants were enrolled at 12 medical center sites, and raters were blinded to diagnostic group. We hypothesized that individuals with SCA would exhibit reductions in frontal lobe cortex thickness and reduced basal ganglia and thalamus volumes compared with HCs and that these structural brain abnormalities would be associated with measures of cognitive functioning (Wechsler Adult Intelligence Scale, 3rd edition). Results: After adjusting for age, sex, education level, and intracranial volume, participants with SCA exhibited thinner frontal lobe cortex (t = −2.99, p = 0.003) and reduced basal ganglia and thalamus volumes compared with HCs (t = −3.95, p < 0.001). Reduced volume of the basal ganglia and thalamus was significantly associated with lower Performance IQ (model estimate = 3.75, p = 0.004) as well as lower Perceptual Organization (model estimate = 1.44, p = 0.007) and Working Memory scores (model estimate = 1.37, p = 0.015). Frontal lobe cortex thickness was not significantly associated with any cognitive measures. Conclusions: Our findings suggest that basal ganglia and thalamus abnormalities may represent a particularly salient contributor to cognitive dysfunction in adults with SCA. PMID:24523480

  5. Visuo-Motor and Cognitive Procedural Learning in Children with Basal Ganglia Pathology

    ERIC Educational Resources Information Center

    Mayor-Dubois, C.; Maeder, P.; Zesiger, P.; Roulet-Perez, E.

    2010-01-01

    We investigated procedural learning in 18 children with basal ganglia (BG) lesions or dysfunctions of various aetiologies, using a visuo-motor learning test, the Serial Reaction Time (SRT) task, and a cognitive learning test, the Probabilistic Classification Learning (PCL) task. We compared patients with early (less than 1 year old, n=9), later…

  6. Insights into Parkinson's disease from computational models of the basal ganglia.

    PubMed

    Humphries, Mark D; Obeso, Jose Angel; Dreyer, Jakob Kisbye

    2018-04-17

    Movement disorders arise from the complex interplay of multiple changes to neural circuits. Successful treatments for these disorders could interact with these complex changes in myriad ways, and as a consequence their mechanisms of action and their amelioration of symptoms are incompletely understood. Using Parkinson's disease as a case study, we review here how computational models are a crucial tool for taming this complexity, across causative mechanisms, consequent neural dynamics and treatments. For mechanisms, we review models that capture the effects of losing dopamine on basal ganglia function; for dynamics, we discuss models that have transformed our understanding of how beta-band (15-30 Hz) oscillations arise in the parkinsonian basal ganglia. For treatments, we touch on the breadth of computational modelling work trying to understand the therapeutic actions of deep brain stimulation. Collectively, models from across all levels of description are providing a compelling account of the causes, symptoms and treatments for Parkinson's disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Neural Representation of a Target Auditory Memory in a Cortico-Basal Ganglia Pathway

    PubMed Central

    Bottjer, Sarah W.

    2013-01-01

    Vocal learning in songbirds, like speech acquisition in humans, entails a period of sensorimotor integration during which vocalizations are evaluated via auditory feedback and progressively refined to achieve an imitation of memorized vocal sounds. This process requires the brain to compare feedback of current vocal behavior to a memory of target vocal sounds. We report the discovery of two distinct populations of neurons in a cortico-basal ganglia circuit of juvenile songbirds (zebra finches, Taeniopygia guttata) during vocal learning: (1) one in which neurons are selectively tuned to memorized sounds and (2) another in which neurons are selectively tuned to self-produced vocalizations. These results suggest that neurons tuned to learned vocal sounds encode a memory of those target sounds, whereas neurons tuned to self-produced vocalizations encode a representation of current vocal sounds. The presence of neurons tuned to memorized sounds is limited to early stages of sensorimotor integration: after learning, the incidence of neurons encoding memorized vocal sounds was greatly diminished. In contrast to this circuit, neurons known to drive vocal behavior through a parallel cortico-basal ganglia pathway show little selective tuning until late in learning. One interpretation of these data is that representations of current and target vocal sounds in the shell circuit are used to compare ongoing patterns of vocal feedback to memorized sounds, whereas the parallel core circuit has a motor-related role in learning. Such a functional subdivision is similar to mammalian cortico-basal ganglia pathways in which associative-limbic circuits mediate goal-directed responses, whereas sensorimotor circuits support motor aspects of learning. PMID:24005299

  8. PreSMA stimulation changes task-free functional connectivity in the fronto-basal-ganglia that correlates with response inhibition efficiency

    PubMed Central

    Xu, Benjamin; Sandrini, Marco; Wang, Wen-tung; Smith, Jason F.; Sarlls, Joelle E.; Awosika, Oluwole; Butman, John A.; Horwitz, Barry; Cohen, Leonardo G.

    2016-01-01

    Previous work using transcranial magnetic stimulation (TMS) demonstrated that the right pre-supplementary motor area (preSMA), a node in the fronto-basal-ganglia network, is critical for response inhibition. However, TMS influences interconnected regions, raising the possibility of a link between the preSMA activity and the functional connectivity within the network. To understand this relationship, we applied single-pulse TMS to the right preSMA during functional magnetic resonance imaging when the subjects were at rest to examine changes in neural activity and functional connectivity within the network in relation to the efficiency of response inhibition evaluated with a stop-signal task. The results showed that preSMA-TMS increased activation in the right inferior-frontal cortex (rIFC) and basal ganglia and modulated their task-free functional connectivity. Both the TMS-induced changes in the basal-ganglia activation and the functional connectivity between rIFC and left striatum, and of the overall network correlated with the efficiency of response inhibition and with the white-matter microstructure along the preSMA – rIFC pathway. These results suggest that the task-free functional and structural connectivity between the rIFCop and basal ganglia are critical to the efficiency of response inhibition. PMID:27144466

  9. Age-related changes in HSP25 expression in basal ganglia and cortex of F344/BN rats

    PubMed Central

    Gupte, Anisha A.; Morris, Jill K.; Zhang, Hongyu; Bomhoff, Gregory L.; Geiger, Paige C.; Stanford, John A.

    2010-01-01

    Normal aging is associated with chronic oxidative stress. In the basal ganglia, oxidative stress may contribute to the increased risk of Parkinson's disease in the elderly. Neurons are thought to actively utilize compensatory defense mechanisms, such as heat shock proteins (HSPs), to protect from persisting stress. Despite their protective role, little is known about HSP expression in the aging basal ganglia. The purpose of this study was to examine HSP expression in striatum, substantia nigra, globus pallidus and cortex in 6-, 18- and 30-month-old Fischer 344/Brown Norway rats. We found robust age-related increases in phosphorylated and total HSP25 in each brain region studied. Conversely, HSP72 (the inducible form of HSP70) was reduced with age, but only in the striatum. p38 MAPK, a protein implicated in activating HSP25, did not change with age, nor did HSC70 (the constitutive form of HSP70), or HSP60. These results suggest that HSP25 is especially responsive to age-related stress in the basal ganglia. PMID:20144690

  10. Vocal learning, prosody, and basal ganglia: don't underestimate their complexity.

    PubMed

    Ravignani, Andrea; Martins, Mauricio; Fitch, W Tecumseh

    2014-12-01

    Ackermann et al.'s arguments in the target article need sharpening and rethinking at both mechanistic and evolutionary levels. First, the authors' evolutionary arguments are inconsistent with recent evidence concerning nonhuman animal rhythmic abilities. Second, prosodic intonation conveys much more complex linguistic information than mere emotional expression. Finally, human adults' basal ganglia have a considerably wider role in speech modulation than Ackermann et al. surmise.

  11. A Pause-then-Cancel model of stopping: evidence from basal ganglia neurophysiology

    PubMed Central

    Berke, Joshua D.

    2017-01-01

    Many studies have implicated the basal ganglia in the suppression of action impulses (‘stopping’). Here, we discuss recent neurophysiological evidence that distinct hypothesized processes involved in action preparation and cancellation can be mapped onto distinct basal ganglia cell types and pathways. We examine how movement-related activity in the striatum is related to a ‘Go’ process and how going may be modulated by brief epochs of beta oscillations. We then describe how, rather than a unitary ‘Stop’ process, there appear to be separate, complementary ‘Pause’ and ‘Cancel’ mechanisms. We discuss the implications of these stopping subprocesses for the interpretation of the stop-signal reaction time—in particular, some activity that seems too slow to causally contribute to stopping when assuming a single Stop processes may actually be fast enough under a Pause-then-Cancel model. Finally, we suggest that combining complementary neural mechanisms that emphasize speed or accuracy respectively may serve more generally to optimize speed–accuracy trade-offs. This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’. PMID:28242736

  12. A Pause-then-Cancel model of stopping: evidence from basal ganglia neurophysiology.

    PubMed

    Schmidt, Robert; Berke, Joshua D

    2017-04-19

    Many studies have implicated the basal ganglia in the suppression of action impulses ('stopping'). Here, we discuss recent neurophysiological evidence that distinct hypothesized processes involved in action preparation and cancellation can be mapped onto distinct basal ganglia cell types and pathways. We examine how movement-related activity in the striatum is related to a 'Go' process and how going may be modulated by brief epochs of beta oscillations. We then describe how, rather than a unitary 'Stop' process, there appear to be separate, complementary 'Pause' and 'Cancel' mechanisms. We discuss the implications of these stopping subprocesses for the interpretation of the stop-signal reaction time-in particular, some activity that seems too slow to causally contribute to stopping when assuming a single Stop processes may actually be fast enough under a Pause-then-Cancel model. Finally, we suggest that combining complementary neural mechanisms that emphasize speed or accuracy respectively may serve more generally to optimize speed-accuracy trade-offs.This article is part of the themed issue 'Movement suppression: brain mechanisms for stopping and stillness'. © 2017 The Author(s).

  13. Amnesia Associated with Bilateral Hippocampal and Bilateral Basal Ganglia Lesions in Anoxia with Stimulant Use

    PubMed Central

    Haut, Marc W.; Hogg, Jeffery P.; Marshalek, Patrick J.; Suter, Blair C.; Miller, Liv E.

    2017-01-01

    We report a case of a 55-year-old man with ischemic lesions of the bilateral hippocampus and bilateral basal ganglia following a myocardial infarction during an episode of multiple drug use with subsequent anoxia requiring resuscitation. He presented for a neuropsychological evaluation with an anterograde amnesia for both explicit and procedural memory. There are two main points to this case, the unique aspects of the bilateral multifocal lesions and the functional, cognitive impact of these lesions. We hypothesize that his rare focal bilateral lesions of both the hippocampus and basal ganglia are a result of anoxia acting in synergy with his stimulant drug use (cocaine and/or 3,4-methylenedioxy-methamphetamine). Second, his unique lesions produced an explicit and implicit/procedural anterograde amnesia. PMID:28228745

  14. Amnesia Associated with Bilateral Hippocampal and Bilateral Basal Ganglia Lesions in Anoxia with Stimulant Use.

    PubMed

    Haut, Marc W; Hogg, Jeffery P; Marshalek, Patrick J; Suter, Blair C; Miller, Liv E

    2017-01-01

    We report a case of a 55-year-old man with ischemic lesions of the bilateral hippocampus and bilateral basal ganglia following a myocardial infarction during an episode of multiple drug use with subsequent anoxia requiring resuscitation. He presented for a neuropsychological evaluation with an anterograde amnesia for both explicit and procedural memory. There are two main points to this case, the unique aspects of the bilateral multifocal lesions and the functional, cognitive impact of these lesions. We hypothesize that his rare focal bilateral lesions of both the hippocampus and basal ganglia are a result of anoxia acting in synergy with his stimulant drug use (cocaine and/or 3,4-methylenedioxy-methamphetamine). Second, his unique lesions produced an explicit and implicit/procedural anterograde amnesia.

  15. Listening to Rhythmic Music Reduces Connectivity within the Basal Ganglia and the Reward System.

    PubMed

    Brodal, Hans P; Osnes, Berge; Specht, Karsten

    2017-01-01

    Music can trigger emotional responses in a more direct way than any other stimulus. In particular, music-evoked pleasure involves brain networks that are part of the reward system. Furthermore, rhythmic music stimulates the basal ganglia and may trigger involuntary movements to the beat. In the present study, we created a continuously playing rhythmic, dance floor-like composition where the ambient noise from the MR scanner was incorporated as an additional instrument of rhythm. By treating this continuous stimulation paradigm as a variant of resting-state, the data was analyzed with stochastic dynamic causal modeling (sDCM), which was used for exploring functional dependencies and interactions between core areas of auditory perception, rhythm processing, and reward processing. The sDCM model was a fully connected model with the following areas: auditory cortex, putamen/pallidum, and ventral striatum/nucleus accumbens of both hemispheres. The resulting estimated parameters were compared to ordinary resting-state data, without an additional continuous stimulation. Besides reduced connectivity within the basal ganglia, the results indicated a reduced functional connectivity of the reward system, namely the right ventral striatum/nucleus accumbens from and to the basal ganglia and auditory network while listening to rhythmic music. In addition, the right ventral striatum/nucleus accumbens demonstrated also a change in its hemodynamic parameter, reflecting an increased level of activation. These converging results may indicate that the dopaminergic reward system reduces its functional connectivity and relinquishing its constraints on other areas when we listen to rhythmic music.

  16. Prefrontal Activity and Connectivity with the Basal Ganglia during Performance of Complex Cognitive Tasks Is Associated with Apathy in Healthy Subjects.

    PubMed

    Fazio, Leonardo; Logroscino, Giancarlo; Taurisano, Paolo; Amico, Graziella; Quarto, Tiziana; Antonucci, Linda Antonella; Barulli, Maria Rosaria; Mancini, Marina; Gelao, Barbara; Ferranti, Laura; Popolizio, Teresa; Bertolino, Alessandro; Blasi, Giuseppe

    2016-01-01

    Convergent evidence indicates that apathy affects cognitive behavior in different neurological and psychiatric conditions. Studies of clinical populations have also suggested the primary involvement of the prefrontal cortex and the basal ganglia in apathy. These brain regions are interconnected at both the structural and functional levels and are deeply involved in cognitive processes, such as working memory and attention. However, it is unclear how apathy modulates brain processing during cognition and whether such a modulation occurs in healthy young subjects. To address this issue, we investigated the link between apathy and prefrontal and basal ganglia function in healthy young individuals. We hypothesized that apathy may be related to sub-optimal activity and connectivity in these brain regions. Three hundred eleven healthy subjects completed an apathy assessment using the Starkstein's Apathy Scale and underwent fMRI during working memory and attentional performance tasks. Using an ROI approach, we investigated the association of apathy with activity and connectivity in the DLPFC and the basal ganglia. Apathy scores correlated positively with prefrontal activity and negatively with prefrontal-basal ganglia connectivity during both working memory and attention tasks. Furthermore, prefrontal activity was inversely related to attentional behavior. These results suggest that in healthy young subjects, apathy is a trait associated with inefficient cognitive-related prefrontal activity, i.e., it increases the need for prefrontal resources to process cognitive stimuli. Furthermore, apathy may alter the functional relationship between the prefrontal cortex and the basal ganglia during cognition.

  17. A Case of Suspicious Gangliocytoma with Heterogeneously Distributed Lesions in the Thalamus and Basal Ganglia.

    PubMed

    Miyake, Yohei; Mishima, Kazuhiko; Suzuki, Tomonari; Adachi, Jun-Ichi; Sasaki, Atsushi; Nishikawa, Ryo

    2018-04-01

    We report a case of a 24-year-old woman who presented with an uncomfortable feeling in her right foot with a 6-month history of slight weakness in her right hand. Neuroimaging demonstrated irregular shaped lesions in the left thalamus and basal ganglia in addition to spotty lesions in the contralateral thalamus. The MRI showed high-intensity signals on T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted images. The lesions demonstrated low-intensity signaling on T1-weighted images and were slightly enhanced with gadolinium. Other examinations including positron emission tomography, MR spectroscopy, and laboratory tests did not reveal any specific information regarding the lesions. The biopsied specimens, from the left basal ganglia, revealed proliferation of dysplastic neuronal cells without any neoplastic glial elements; thus, gangliocytoma (WHO grade I) was the most likely diagnosis. The patient was further observed based on this diagnosis of suspicious gangliocytoma, and the follow-up MRI, performed a year after the biopsy, revealed that the disease was stable. To our knowledge, gangliocytoma in the thalamus and basal ganglia have not been reported. Additionally, the findings of the magnetic resonance imaging (MRI) in this case were unique and different from those previously reported in cases of gangliocytoma. The authors report this unique case and discuss the radiological, pathological, and genetic findings.

  18. A Case of Suspicious Gangliocytoma with Heterogeneously Distributed Lesions in the Thalamus and Basal Ganglia

    PubMed Central

    Miyake, Yohei; Mishima, Kazuhiko; Suzuki, Tomonari; Adachi, Jun-ichi; Sasaki, Atsushi; Nishikawa, Ryo

    2018-01-01

    We report a case of a 24-year-old woman who presented with an uncomfortable feeling in her right foot with a 6-month history of slight weakness in her right hand. Neuroimaging demonstrated irregular shaped lesions in the left thalamus and basal ganglia in addition to spotty lesions in the contralateral thalamus. The MRI showed high-intensity signals on T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted images. The lesions demonstrated low-intensity signaling on T1-weighted images and were slightly enhanced with gadolinium. Other examinations including positron emission tomography, MR spectroscopy, and laboratory tests did not reveal any specific information regarding the lesions. The biopsied specimens, from the left basal ganglia, revealed proliferation of dysplastic neuronal cells without any neoplastic glial elements; thus, gangliocytoma (WHO grade I) was the most likely diagnosis. The patient was further observed based on this diagnosis of suspicious gangliocytoma, and the follow-up MRI, performed a year after the biopsy, revealed that the disease was stable. To our knowledge, gangliocytoma in the thalamus and basal ganglia have not been reported. Additionally, the findings of the magnetic resonance imaging (MRI) in this case were unique and different from those previously reported in cases of gangliocytoma. The authors report this unique case and discuss the radiological, pathological, and genetic findings. PMID:29725570

  19. PreSMA stimulation changes task-free functional connectivity in the fronto-basal-ganglia that correlates with response inhibition efficiency.

    PubMed

    Xu, Benjamin; Sandrini, Marco; Wang, Wen-Tung; Smith, Jason F; Sarlls, Joelle E; Awosika, Oluwole; Butman, John A; Horwitz, Barry; Cohen, Leonardo G

    2016-09-01

    Previous work using transcranial magnetic stimulation (TMS) demonstrated that the right presupplementary motor area (preSMA), a node in the fronto-basal-ganglia network, is critical for response inhibition. However, TMS influences interconnected regions, raising the possibility of a link between the preSMA activity and the functional connectivity within the network. To understand this relationship, we applied single-pulse TMS to the right preSMA during functional magnetic resonance imaging when the subjects were at rest to examine changes in neural activity and functional connectivity within the network in relation to the efficiency of response inhibition evaluated with a stop-signal task. The results showed that preSMA-TMS increased activation in the right inferior-frontal cortex (rIFC) and basal ganglia and modulated their task-free functional connectivity. Both the TMS-induced changes in the basal-ganglia activation and the functional connectivity between rIFC and left striatum, and of the overall network correlated with the efficiency of response inhibition and with the white-matter microstructure along the preSMA-rIFC pathway. These results suggest that the task-free functional and structural connectivity between the rIFCop and basal ganglia are critical to the efficiency of response inhibition. Hum Brain Mapp 37:3236-3249, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Frequency and function in the basal ganglia: the origins of beta and gamma band activity.

    PubMed

    Blenkinsop, Alexander; Anderson, Sean; Gurney, Kevin

    2017-07-01

    Neuronal oscillations in the basal ganglia have been observed to correlate with behaviours, although the causal mechanisms and functional significance of these oscillations remain unknown. We present a novel computational model of the healthy basal ganglia, constrained by single unit recordings from non-human primates. When the model is run using inputs that might be expected during performance of a motor task, the network shows emergent phenomena: it functions as a selection mechanism and shows spectral properties that match those seen in vivo. Beta frequency oscillations are shown to require pallido-striatal feedback, and occur with behaviourally relevant cortical input. Gamma oscillations arise in the subthalamic-globus pallidus feedback loop, and occur during movement. The model provides a coherent framework for the study of spectral, temporal and functional analyses of the basal ganglia and lays the foundation for an integrated approach to study basal ganglia pathologies such as Parkinson's disease in silico. Neural oscillations in the basal ganglia (BG) are well studied yet remain poorly understood. Behavioural correlates of spectral activity are well described, yet a quantitative hypothesis linking time domain dynamics and spectral properties to BG function has been lacking. We show, for the first time, that a unified description is possible by interpreting previously ignored structure in data describing globus pallidus interna responses to cortical stimulation. These data were used to expose a pair of distinctive neuronal responses to the stimulation. This observation formed the basis for a new mathematical model of the BG, quantitatively fitted to the data, which describes the dynamics in the data, and is validated against other stimulus protocol experiments. A key new result is that when the model is run using inputs hypothesised to occur during the performance of a motor task, beta and gamma frequency oscillations emerge naturally during static-force and

  1. Prefrontal Activity and Connectivity with the Basal Ganglia during Performance of Complex Cognitive Tasks Is Associated with Apathy in Healthy Subjects

    PubMed Central

    Fazio, Leonardo; Logroscino, Giancarlo; Taurisano, Paolo; Amico, Graziella; Quarto, Tiziana; Antonucci, Linda Antonella; Barulli, Maria Rosaria; Mancini, Marina; Gelao, Barbara; Ferranti, Laura; Popolizio, Teresa; Bertolino, Alessandro; Blasi, Giuseppe

    2016-01-01

    Objective Convergent evidence indicates that apathy affects cognitive behavior in different neurological and psychiatric conditions. Studies of clinical populations have also suggested the primary involvement of the prefrontal cortex and the basal ganglia in apathy. These brain regions are interconnected at both the structural and functional levels and are deeply involved in cognitive processes, such as working memory and attention. However, it is unclear how apathy modulates brain processing during cognition and whether such a modulation occurs in healthy young subjects. To address this issue, we investigated the link between apathy and prefrontal and basal ganglia function in healthy young individuals. We hypothesized that apathy may be related to sub-optimal activity and connectivity in these brain regions. Methods Three hundred eleven healthy subjects completed an apathy assessment using the Starkstein’s Apathy Scale and underwent fMRI during working memory and attentional performance tasks. Using an ROI approach, we investigated the association of apathy with activity and connectivity in the DLPFC and the basal ganglia. Results Apathy scores correlated positively with prefrontal activity and negatively with prefrontal-basal ganglia connectivity during both working memory and attention tasks. Furthermore, prefrontal activity was inversely related to attentional behavior. Conclusions These results suggest that in healthy young subjects, apathy is a trait associated with inefficient cognitive-related prefrontal activity, i.e., it increases the need for prefrontal resources to process cognitive stimuli. Furthermore, apathy may alter the functional relationship between the prefrontal cortex and the basal ganglia during cognition. PMID:27798669

  2. Listening to Rhythmic Music Reduces Connectivity within the Basal Ganglia and the Reward System

    PubMed Central

    Brodal, Hans P.; Osnes, Berge; Specht, Karsten

    2017-01-01

    Music can trigger emotional responses in a more direct way than any other stimulus. In particular, music-evoked pleasure involves brain networks that are part of the reward system. Furthermore, rhythmic music stimulates the basal ganglia and may trigger involuntary movements to the beat. In the present study, we created a continuously playing rhythmic, dance floor-like composition where the ambient noise from the MR scanner was incorporated as an additional instrument of rhythm. By treating this continuous stimulation paradigm as a variant of resting-state, the data was analyzed with stochastic dynamic causal modeling (sDCM), which was used for exploring functional dependencies and interactions between core areas of auditory perception, rhythm processing, and reward processing. The sDCM model was a fully connected model with the following areas: auditory cortex, putamen/pallidum, and ventral striatum/nucleus accumbens of both hemispheres. The resulting estimated parameters were compared to ordinary resting-state data, without an additional continuous stimulation. Besides reduced connectivity within the basal ganglia, the results indicated a reduced functional connectivity of the reward system, namely the right ventral striatum/nucleus accumbens from and to the basal ganglia and auditory network while listening to rhythmic music. In addition, the right ventral striatum/nucleus accumbens demonstrated also a change in its hemodynamic parameter, reflecting an increased level of activation. These converging results may indicate that the dopaminergic reward system reduces its functional connectivity and relinquishing its constraints on other areas when we listen to rhythmic music. PMID:28400717

  3. Alterations of the cerebellum and basal ganglia in bipolar disorder mood states detected by quantitative T1ρ mapping.

    PubMed

    Johnson, Casey P; Christensen, Gary E; Fiedorowicz, Jess G; Mani, Merry; Shaffer, Joseph J; Magnotta, Vincent A; Wemmie, John A

    2018-06-01

    Quantitative mapping of T1 relaxation in the rotating frame (T1ρ) is a magnetic resonance imaging technique sensitive to pH and other cellular and microstructural factors, and is a potentially valuable tool for identifying brain alterations in bipolar disorder. Recently, this technique identified differences in the cerebellum and cerebral white matter of euthymic patients vs healthy controls that were consistent with reduced pH in these regions, suggesting an underlying metabolic abnormality. The current study built upon this prior work to investigate brain T1ρ differences across euthymic, depressed, and manic mood states of bipolar disorder. Forty participants with bipolar I disorder and 29 healthy control participants matched for age and gender were enrolled. Participants with bipolar disorder were imaged in one or more mood states, yielding 27, 12, and 13 imaging sessions in euthymic, depressed, and manic mood states, respectively. Three-dimensional, whole-brain anatomical images and T1ρ maps were acquired for all participants, enabling voxel-wise evaluation of T1ρ differences between bipolar mood state and healthy control groups. All three mood state groups had increased T1ρ relaxation times in the cerebellum compared to the healthy control group. Additionally, the depressed and manic groups had reduced T1ρ relaxation times in and around the basal ganglia compared to the control and euthymic groups. The study implicated the cerebellum and basal ganglia in the pathophysiology of bipolar disorder and its mood states, the roles of which are relatively unexplored. These findings motivate further investigation of the underlying cause of the abnormalities, and the potential role of altered metabolic activity in these regions. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome: correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels.

    PubMed

    Haley, R W; Fleckenstein, J L; Marshall, W W; McDonald, G G; Kramer, G L; Petty, F

    2000-09-01

    Many complaints of Gulf War veterans are compatible with a neurologic illness involving the basal ganglia. In 12 veterans with Haley Gulf War syndrome 2 and in 15 healthy control veterans of similar age, sex, and educational level, we assessed functioning neuronal mass in both basal ganglia by measuring the ratio of N-acetyl-aspartate to creatine with proton magnetic resonance spectroscopy. Central dopamine activity was assessed by measuring the ratio of plasma homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenlyglycol (MHPG). The logarithm of the age-standardized HVA/MHPG ratio was inversely associated with functioning neuronal mass in the left basal ganglia (R(2) = 0.56; F(1,27) = 33.82; P<.001) but not with that in the right (R(2) = 0. 04; F(1,26) = 1.09; P =.30). Controlling for age, renal clearances of creatinine and weak organic anions, handedness, and smoking did not substantially alter the associations. The reduction in functioning neuronal mass in the left basal ganglia of these veterans with Gulf War syndrome seems to have altered central dopamine production in a lateralized pattern. This finding supports the theory that Gulf War syndrome is a neurologic illness, in part related to injury to dopaminergic neurons in the basal ganglia.

  5. Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model

    PubMed Central

    2016-01-01

    Abstract The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson’s disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model. Simulation experiments predict that both local inhibition in striatum and the existence of an indirect pathway are important for basal ganglia to function properly over a large range of cortical drives. The dopamine depletion–induced increase of AMPA efficacy in corticostriatal synapses to medium spiny neurons (MSNs) with dopamine receptor D2 synapses (CTX-MSN D2) and the reduction of MSN lateral connectivity (MSN–MSN) were found to contribute significantly to the enhanced synchrony and oscillations seen in PD. Additionally, reversing the dopamine depletion–induced changes to CTX–MSN D1, CTX–MSN D2, TA–MSN, and MSN–MSN couplings could improve or restore basal ganglia action selection ability. In summary, we found multiple changes of parameters for synaptic efficacy and neural excitability that could improve action selection ability and at the same time reduce oscillations. Identification of such targets could potentially generate ideas for treatments of PD and increase our understanding of the relation between network dynamics and network function. PMID:28101525

  6. Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model.

    PubMed

    Lindahl, Mikael; Hellgren Kotaleski, Jeanette

    2016-01-01

    The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson's disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model. Simulation experiments predict that both local inhibition in striatum and the existence of an indirect pathway are important for basal ganglia to function properly over a large range of cortical drives. The dopamine depletion-induced increase of AMPA efficacy in corticostriatal synapses to medium spiny neurons (MSNs) with dopamine receptor D2 synapses (CTX-MSN D2) and the reduction of MSN lateral connectivity (MSN-MSN) were found to contribute significantly to the enhanced synchrony and oscillations seen in PD. Additionally, reversing the dopamine depletion-induced changes to CTX-MSN D1, CTX-MSN D2, TA-MSN, and MSN-MSN couplings could improve or restore basal ganglia action selection ability. In summary, we found multiple changes of parameters for synaptic efficacy and neural excitability that could improve action selection ability and at the same time reduce oscillations. Identification of such targets could potentially generate ideas for treatments of PD and increase our understanding of the relation between network dynamics and network function.

  7. Deep intracerebral (basal ganglia) haematomas in fatal non-missile head injury in man.

    PubMed Central

    Adams, J H; Doyle, D; Graham, D I; Lawrence, A E; McLellan, D R

    1986-01-01

    Deep intracerebral (basal ganglia) haematomas were found post mortem in 63 of 635 fatal non-missile head injuries. In patients with a basal ganglia haematoma, contusions were more severe, there was a reduced incidence of a lucid interval, and there was an increased incidence of road traffic accidents, gliding contusions and diffuse axonal injury than in patients without this type of haematoma. Intracranial haematoma is usually thought to be a secondary event, that is a complication of the original injury, but these results suggest that a deep intracerebral haematoma is a primary event. If a deep intracerebral haematoma is identified on an early CT scan it is likely that the patient has sustained severe diffuse brain damage at the time of injury. In the majority of head injuries damage to blood vessels or axons predominates. In patients with a traumatic deep intracerebral haematoma, it would appear that the deceleration/acceleration forces are such that both axons and blood vessels within the brain are damaged at the time of injury. Images PMID:3760892

  8. Interaction between basal ganglia and limbic circuits in learning and memory processes.

    PubMed

    Calabresi, Paolo; Picconi, Barbara; Tozzi, Alessandro; Ghiglieri, Veronica

    2016-01-01

    Hippocampus and striatum play distinctive roles in memory processes since declarative and non-declarative memory systems may act independently. However, hippocampus and striatum can also be engaged to function in parallel as part of a dynamic system to integrate previous experience and adjust behavioral responses. In these structures the formation, storage, and retrieval of memory require a synaptic mechanism that is able to integrate multiple signals and to translate them into persistent molecular traces at both the corticostriatal and hippocampal/limbic synapses. The best cellular candidate for this complex synthesis is represented by long-term potentiation (LTP). A common feature of LTP expressed in these two memory systems is the critical requirement of convergence and coincidence of glutamatergic and dopaminergic inputs to the dendritic spines of the neurons expressing this form of synaptic plasticity. In experimental models of Parkinson's disease abnormal accumulation of α-synuclein affects these two memory systems by altering two major synaptic mechanisms underlying cognitive functions in cholinergic striatal neurons, likely implicated in basal ganglia dependent operative memory, and in the CA1 hippocampal region, playing a central function in episodic/declarative memory processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Electrocorticography reveals beta desynchronization in the basal ganglia-cortical loop during rest tremor in Parkinson's disease.

    PubMed

    Qasim, Salman E; de Hemptinne, Coralie; Swann, Nicole C; Miocinovic, Svjetlana; Ostrem, Jill L; Starr, Philip A

    2016-02-01

    The pathophysiology of rest tremor in Parkinson's disease (PD) is not well understood, and its severity does not correlate with the severity of other cardinal signs of PD. We hypothesized that tremor-related oscillatory activity in the basal-ganglia-thalamocortical loop might serve as a compensatory mechanism for the excessive beta band synchronization associated with the parkinsonian state. We recorded electrocorticography (ECoG) from the sensorimotor cortex and local field potentials (LFP) from the subthalamic nucleus (STN) in patients undergoing lead implantation for deep brain stimulation (DBS). We analyzed differences in measures of network synchronization during epochs of spontaneous rest tremor, versus epochs without rest tremor, occurring in the same subjects. The presence of tremor was associated with reduced beta power in the cortex and STN. Cortico-cortical coherence and phase-amplitude coupling (PAC) decreased during rest tremor, as did basal ganglia-cortical coherence in the same frequency band. Cortical broadband gamma power was not increased by tremor onset, in contrast to the movement-related gamma increase typically observed at the onset of voluntary movement. These findings suggest that the cortical representation of rest tremor is distinct from that of voluntary movement, and support a model in which tremor acts to decrease beta band synchronization within the basal ganglia-cortical loop. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. [Pathology of basal ganglia in neurodegenerative diseases].

    PubMed

    Wakabayashi, Koichi; Tanji, Kunikazu; Mori, Fumiaki

    2009-04-01

    Intra- and/or extracellular proteinaceous inclusions in the brain tissue are characteristic pathological markers of many neurodegenerative diseases. Tau protein in neurofibrillary tangles and beta-amyloid in senile plaques are associated with Alzheimer's disease. Tau is associated with various neurological conditions, which are collectively referred to as tauopathies. Alpha-synucleinopathy is a term that collectively refers to a set of diseases in which neurodegeneration is accompanied by intracellular accumulation of alpha-synuclein in neurons or glial cells. Recently, TDP-43 has been identified as a major disease protein in the ubiquitinated inclusions in deseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration with tau-negative, ubiquitin-positive inclusions. Thus, these neurodegenerative disorders comprise a new disease class, namely, TDP-43 proteinopathy. In this article, we review the present understanding of histopathological features of basal ganglia lesions in protein conformation disorders, including tauopathy, alpha-synucleinopathy, and TDP-43 proteinopathy.

  11. Electrocorticography reveals beta desynchronization in the basal ganglia-cortical loop during rest tremor in Parkinson’s disease

    PubMed Central

    Qasim, Salman E.; de Hemptinne, Coralie; Swann, Nicole C.; Miocinovic, Svjetlana; Ostrem, Jill L.; Starr, Philip A.

    2015-01-01

    The pathophysiology of rest tremor in Parkinson’s disease (PD) is not well understood, and its severity does not correlate with the severity of other cardinal signs of PD. We hypothesized that tremor-related oscillatory activity in the basal-ganglia-thalamocortical loop might serve as a compensatory mechanism for the excessive beta band synchronization associated with the parkinsonian state. We recorded electrocorticography (ECoG) from the sensorimotor cortex and local field potentials (LFP) from the subthalamic nucleus (STN) in patients undergoing lead implantation for deep brain stimulation (DBS). We analyzed differences in measures of network synchronization during epochs of spontaneous rest tremor, versus epochs without rest tremor, occurring in the same subjects. The presence of tremor was associated with reduced beta power in the cortex and STN. Cortico-cortical coherence and phase-amplitude coupling (PAC) decreased during rest tremor, as did basal ganglia-cortical coherence in the same frequency band. Cortical broadband gamma power was not increased by tremor onset, in contrast to the movement-related gamma increase typically observed at the onset of voluntary movement. These findings suggest that the cortical representation of rest tremor is distinct from that of voluntary movement, and support a model in which tremor acts to decrease beta band synchronization within the basal ganglia-cortical loop. PMID:26639855

  12. Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems.

    PubMed

    Schmahmann, Jeremy D; Pandya, Deepak N

    2008-09-01

    Disconnection syndromes were originally conceptualized as a disruption of communication between different cerebral cortical areas. Two developments mandate a re-evaluation of this notion. First, we present a synopsis of our anatomical studies in monkey elucidating principles of organization of cerebral cortex. Efferent fibers emanate from every cortical area, and are directed with topographic precision via association fibers to ipsilateral cortical areas, commissural fibers to contralateral cerebral regions, striatal fibers to basal ganglia, and projection subcortical bundles to thalamus, brainstem and/or pontocerebellar system. We note that cortical areas can be defined by their patterns of subcortical and cortical connections. Second, we consider motor, cognitive and neuropsychiatric disorders in patients with lesions restricted to basal ganglia, thalamus, or cerebellum, and recognize that these lesions mimic deficits resulting from cortical lesions, with qualitative differences between the manifestations of lesions in functionally related areas of cortical and subcortical nodes. We consider these findings on the basis of anatomical observations from tract tracing studies in monkey, viewing them as disconnection syndromes reflecting loss of the contribution of subcortical nodes to the distributed neural circuits. We introduce a new theoretical framework for the distributed neural circuits, based on general, and specific, principles of anatomical organization, and on the architecture of the nodes that comprise these systems. We propose that neural architecture determines function, i.e., each architectonically distinct cortical and subcortical area contributes a unique transform, or computation, to information processing; anatomically precise and segregated connections between nodes define behavior; and association fiber tracts that link cerebral cortical areas with each other enable the cross-modal integration required for evolved complex behaviors. This model

  13. Temporal Coupling with Cortex Distinguishes Spontaneous Neuronal Activities in Identified Basal Ganglia-Recipient and Cerebellar-Recipient Zones of the Motor Thalamus

    PubMed Central

    Nakamura, Kouichi C.; Sharott, Andrew; Magill, Peter J.

    2014-01-01

    Neurons of the motor thalamus mediate basal ganglia and cerebellar influences on cortical activity. To elucidate the net result of γ-aminobutyric acid-releasing or glutamatergic bombardment of the motor thalamus by basal ganglia or cerebellar afferents, respectively, we recorded the spontaneous activities of thalamocortical neurons in distinct identified “input zones” in anesthetized rats during defined cortical activity states. Unexpectedly, the mean rates and brain state dependencies of the firing of neurons in basal ganglia-recipient zone (BZ) and cerebellar-recipient zone (CZ) were matched during slow-wave activity (SWA) and cortical activation. However, neurons were distinguished during SWA by their firing regularities, low-threshold spike bursts and, more strikingly, by the temporal coupling of their activities to ongoing cortical oscillations. The firing of neurons across the BZ was stronger and more precisely phase-locked to cortical slow (∼1 Hz) oscillations, although both neuron groups preferentially fired at the same phase. In contrast, neurons in BZ and CZ fired at different phases of cortical spindles (7–12 Hz), but with similar strengths of coupled firing. Thus, firing rates do not reflect the predicted inhibitory–excitatory imbalance across the motor thalamus, and input zone-specific temporal coding through oscillatory synchronization with the cortex could partly mediate the different roles of basal ganglia and cerebellum in behavior. PMID:23042738

  14. What basal ganglia changes underlie the parkinsonian state? The significance of neuronal oscillatory activity

    PubMed Central

    Quiroga-Varela, A.; Walters, J.R.; Brazhnik, E.; Marin, C.; Obeso, J.A.

    2014-01-01

    One well accepted functional feature of the parkinsonian state is the recording of enhanced beta oscillatory activity in the basal ganglia. This has been demonstrated in patients with Parkinson's disease (PD) and in animal models such as the rat with 6-hydroxydopamine (6-OHDA)-induced lesion and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, all of which are associated with severe striatal dopamine depletion. Neuronal hyper-synchronization in the beta (or any other) band is not present despite the presence of bradykinetic features in the rat and monkey models, suggesting that increased beta band power may arise when nigro-striatal lesion is advanced and that it is not an essential feature of the early parkinsonian state. Similar observations and conclusions have been previously made for increased neuronal firing rate in the subthalamic and globus pallidus pars interna nuclei. Accordingly, it is suggested that early parkinsonism may be associated with dynamic changes in basal ganglia output activity leading to reduced movement facilitation that may be an earlier feature of the parkinsonian state. PMID:23727447

  15. The Basal Ganglia Striosomes Affect the Modulation of Conflicts by Subliminal Information-Evidence from X-Linked Dystonia Parkinsonism.

    PubMed

    Beste, Christian; Mückschel, Moritz; Rosales, Raymond; Domingo, Aloysius; Lee, Lillian; Ng, Arlene; Klein, Christine; Münchau, Alexander

    2018-07-01

    Cognitive control is relevant when distracting information induces behavioral conflicts. Such conflicts can be produced consciously and by subliminally processed information. Interestingly, both sources of conflict interact suggesting that they share neural mechanisms. Here, we ask whether conjoint effects between different sources of conflict are modulated by microstructural basal ganglia dysfunction. To this end, we carried out an electroencephalography study and examined event-related potentials (ERPs) including source localization using a combined flanker-subliminal priming task in patients with X-linked dystonia Parkinsonism (XDP) and a group of healthy controls. XDP in its early stages is known to predominantly affect the basal ganglia striosomes. The results suggest that conjoint effects between subliminal and conscious sources of conflicts are modulated by the striosomes and were stronger in XDP patients. The neurophysiological data indicate that this effect is related to modulations in conflict monitoring and response selection (N2 ERP) mechanisms engaging the anterior cingulate cortex. Bottom-up perceptual gating, attentional selection, and motor response activation processes in response to the stimuli (P1, N1, and lateralized readiness potential ERPs) were unaffected. Taken together, these data indicate that striosomes modulate the processing of conscious and subliminal sources of conflict suggesting that microstructural basal ganglia properties are relevant for cognitive control.

  16. Unilateral basal-ganglia involvement likely due to valproate-induced hyperammonemic encephalopathy.

    PubMed

    Joardar, Swarnali; Das, Shubhadeep; Chatterjee, Rita; Guha, Gautam; Hasmi, M A

    2012-08-01

    A male child suffering from generalized tonic clonic epilepsy, on treatment with valproate, developed fulminant hepatic failure, hyperammonemia and encephalopathy due to drug toxicity. The most extraordinary feature was his MRI (FLAIR image) of brain which showed unilateral hyperintensities in right putamen and caudate nucleus. The patient recovered on withdrawal of valproate with mild residual left sided athetotic movements during remission. Repeat investigation confirmed an improved MRI imaging and normalised blood ammonia levels. The case report is unique because of unilateral involvement of basal ganglia due to valproate-induced encephalopathy.

  17. Exercise Mode Moderates the Relationship Between Mobility and Basal Ganglia Volume in Healthy Older Adults.

    PubMed

    Nagamatsu, Lindsay S; Weinstein, Andrea M; Erickson, Kirk I; Fanning, Jason; Awick, Elizabeth A; Kramer, Arthur F; McAuley, Edward

    2016-01-01

    To examine whether 12 months of aerobic training (AT) moderated the relationship between change in mobility and change in basal ganglia volume than balance and toning (BAT) exercises in older adults. Secondary analysis of a randomized controlled trial. Champaign-Urbana, Illinois. Community-dwelling older adults (N=101; mean age 66.4). Twelve-month exercise trial with two groups: AT and BAT. Mobility was assessed using the Timed Up and Go test. Basal ganglia (putamen, caudate nucleus, pallidum) was segmented from T1-weighted magnetic resonance images using the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain Software Library Integrated Registration and Segmentation Tool. Measurements were obtained at baseline and trial completion. Hierarchical multiple regression was conducted to examine whether exercise mode moderates the relationship between change in mobility and change in basal ganglia volume over 12 months. Age, sex, and education were included as covariates. Exercise significantly moderated the relationship between change in mobility and change in left putamen volume. Specifically, for the AT group, volume of the left putamen did not change, regardless of change in mobility. Similarly, in the BAT group, those who improved their mobility most over 12 months had no change in left putamen volume, although left putamen volume of those who declined in mobility levels decreased significantly. The primary finding that older adults who engaged in 12 months of BAT training and improved mobility exhibited maintenance of brain volume in an important region responsible for motor control provides compelling evidence that such exercises can contribute to the promotion of functional independence and healthy aging. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  18. Using a hybrid neuron in physiologically inspired models of the basal ganglia.

    PubMed

    Thibeault, Corey M; Srinivasa, Narayan

    2013-01-01

    Our current understanding of the basal ganglia (BG) has facilitated the creation of computational models that have contributed novel theories, explored new functional anatomy and demonstrated results complementing physiological experiments. However, the utility of these models extends beyond these applications. Particularly in neuromorphic engineering, where the basal ganglia's role in computation is important for applications such as power efficient autonomous agents and model-based control strategies. The neurons used in existing computational models of the BG, however, are not amenable for many low-power hardware implementations. Motivated by a need for more hardware accessible networks, we replicate four published models of the BG, spanning single neuron and small networks, replacing the more computationally expensive neuron models with an Izhikevich hybrid neuron. This begins with a network modeling action-selection, where the basal activity levels and the ability to appropriately select the most salient input is reproduced. A Parkinson's disease model is then explored under normal conditions, Parkinsonian conditions and during subthalamic nucleus deep brain stimulation (DBS). The resulting network is capable of replicating the loss of thalamic relay capabilities in the Parkinsonian state and its return under DBS. This is also demonstrated using a network capable of action-selection. Finally, a study of correlation transfer under different patterns of Parkinsonian activity is presented. These networks successfully captured the significant results of the originals studies. This not only creates a foundation for neuromorphic hardware implementations but may also support the development of large-scale biophysical models. The former potentially providing a way of improving the efficacy of DBS and the latter allowing for the efficient simulation of larger more comprehensive networks.

  19. Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

    PubMed

    Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

    2012-11-01

    Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  20. Basal Ganglia Neuronal Activity during Scanning Eye Movements in Parkinson’s Disease

    PubMed Central

    Sieger, Tomáš; Bonnet, Cecilia; Serranová, Tereza; Wild, Jiří; Novák, Daniel; Růžička, Filip; Urgošík, Dušan; Růžička, Evžen; Gaymard, Bertrand; Jech, Robert

    2013-01-01

    The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsońs disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control. PMID:24223158

  1. Bidirectional Plasticity in Striatonigral Synapses: A Switch to Balance Direct and Indirect Basal Ganglia Pathways

    ERIC Educational Resources Information Center

    Aceves, Jose J.; Rueda-Orozco, Pavel E.; Hernandez-Martinez, Ricardo; Galarraga, Elvira; Bargas, Jose

    2011-01-01

    There is no hypothesis to explain how direct and indirect basal ganglia (BG) pathways interact to reach a balance during the learning of motor procedures. Both pathways converge in the substantia nigra pars reticulata (SNr) carrying the result of striatal processing. Unfortunately, the mechanisms that regulate synaptic plasticity in striatonigral…

  2. Toward sophisiticated basal ganglia neuromodulation: review on basal gaglia deep brain stimulation

    PubMed Central

    Da Cunha, Claudio; Boschen, Suelen L.; Gómez-A, Alexander; Ross, Erika K.; Gibson, William S. J.; Min, Hoon-Ki; Lee, Kendall H.; Blaha, Charles D.

    2015-01-01

    This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson’s disease, Huntington’s disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. PMID:25684727

  3. The Role of the Basal Ganglia in Implicit Contextual Learning: A Study of Parkinson's Disease

    ERIC Educational Resources Information Center

    van Asselen, Marieke; Almeida, Ines; Andre, Rui; Januario, Cristina; Goncalves, Antonio Freire; Castelo-Branco, Miguel

    2009-01-01

    Implicit contextual learning refers to the ability to memorize contextual information from our environment. This contextual information can then be used to guide our attention to a specific location. Although the medial temporal lobe is important for this type of learning, the basal ganglia might also be involved considering its role in many…

  4. Associative and sensorimotor cortico-basal ganglia circuit roles in effects of abused drugs.

    PubMed

    Gremel, C M; Lovinger, D M

    2017-01-01

    The mammalian forebrain is characterized by the presence of several parallel cortico-basal ganglia circuits that shape the learning and control of actions. Among these are the associative, limbic and sensorimotor circuits. The function of all of these circuits has now been implicated in responses to drugs of abuse, as well as drug seeking and drug taking. While the limbic circuit has been most widely examined, key roles for the other two circuits in control of goal-directed and habitual instrumental actions related to drugs of abuse have been shown. In this review we describe the three circuits and effects of acute and chronic drug exposure on circuit physiology. Our main emphasis is on drug actions in dorsal striatal components of the associative and sensorimotor circuits. We then review key findings that have implicated these circuits in drug seeking and taking behaviors, as well as drug use disorders. Finally, we consider different models describing how the three cortico-basal ganglia circuits become involved in drug-related behaviors. This topic has implications for drug use disorders and addiction, as treatments that target the balance between the different circuits may be useful for reducing excessive substance use. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  5. Specific contributions of basal ganglia and cerebellum to the neural tracking of rhythm.

    PubMed

    Nozaradan, Sylvie; Schwartze, Michael; Obermeier, Christian; Kotz, Sonja A

    2017-10-01

    How specific brain networks track rhythmic sensory input over time remains a challenge in neuroimaging work. Here we show that subcortical areas, namely the basal ganglia and the cerebellum, specifically contribute to the neural tracking of rhythm. We tested patients with focal lesions in either of these areas and healthy controls by means of electroencephalography (EEG) while they listened to rhythmic sequences known to induce selective neural tracking at a frequency corresponding to the most-often perceived pulse-like beat. Both patients and controls displayed neural responses to the rhythmic sequences. However, these response patterns were different across groups, with patients showing reduced tracking at beat frequency, especially for the more challenging rhythms. In the cerebellar patients, this effect was specific to the rhythm played at a fast tempo, which places high demands on the temporally precise encoding of events. In contrast, basal ganglia patients showed more heterogeneous responses at beat frequency specifically for the most complex rhythm, which requires more internal generation of the beat. These findings provide electrophysiological evidence that these subcortical structures selectively shape the neural representation of rhythm. Moreover, they suggest that the processing of rhythmic auditory input relies on an extended cortico-subcortico-cortical functional network providing specific timing and entrainment sensitivities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Infiltration of the basal ganglia by brain tumors is associated with the development of co-dominant language function on fMRI.

    PubMed

    Shaw, Katharina; Brennan, Nicole; Woo, Kaitlin; Zhang, Zhigang; Young, Robert; Peck, Kyung K; Holodny, Andrei

    2016-01-01

    Studies have shown that some patients with left-hemispheric brain tumors have an increased propensity for developing right-sided language support. However, the precise trigger for establishing co-dominant language function in brain tumor patients remains unknown. We analyzed the MR scans of patients with left-hemispheric tumors and either co-dominant (n=35) or left-hemisphere dominant (n=35) language function on fMRI to investigate anatomical factors influencing hemispheric language dominance. Of eleven neuroanatomical areas evaluated for tumor involvement, the basal ganglia was significantly correlated with co-dominant language function (p<0.001). Moreover, among patients whose tumors invaded the basal ganglia, those with language co-dominance performed significantly better on the Boston Naming Test, a clinical measure of aphasia, compared to their left-lateralized counterparts (56.5 versus 36.5, p=0.025). While further studies are needed to elucidate the role of the basal ganglia in establishing co-dominance, our results suggest that reactive co-dominance may afford a behavioral advantage to patients with left-hemispheric tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Changes in the basal membrane of dorsal root ganglia Schwann cells explain the biphasic pattern of the peripheral neuropathy in streptozotocin-induced diabetic rats.

    PubMed

    Becker, Maria; Benromano, Tali; Shahar, Abraham; Nevo, Zvi; Pick, Chaim G

    2014-12-01

    Peripheral neuropathy is one of the main complications of diabetes mellitus. The current study demonstrated the bimodal pattern of diabetic peripheral neuropathy found in the behavioral study of pain perception in parallel to the histopathological findings in dorsal root ganglia (DRGs) neurons and satellite Schwann cell basement membranes. A gradual decrease in heparan sulfate content, with a reciprocal increase in deposited laminin in the basement membranes of dorsal root ganglia Schwann cells, was shown in streptozotocin-treated rats. In addition, the characteristic biphasic pain profiles were demonstrated in diabetic rats, as shown by hypersensitivity at the third week and hyposensitivity at the tenth week post-streptozotocin injection, accompanied by a continuous decrease in the sciatic nerve conduction velocity. It appears that these basal membrane abnormalities in content of heparan sulfate and laminin, noticed in diabetic rats, may underline the primary damage in dorsal ganglion sensory neurons, simultaneously with the bimodal painful profile in diabetic peripheral neuropathy, simulating the scenario of filtration rate in diabetic kidney.

  8. Neuronal connections of direct and indirect pathways for stable value memory in caudal basal ganglia.

    PubMed

    Amita, Hidetoshi; Kim, Hyoung F; Smith, Mitchell; Gopal, Atul; Hikosaka, Okihide

    2018-05-08

    Direct and indirect pathways in the basal ganglia work together for controlling behavior. However, it is still a controversial topic whether these pathways are segregated or merged with each other. To address this issue, we studied the connections of these two pathways in the caudal parts of the basal ganglia of rhesus monkeys using anatomical tracers. Our previous studies showed that the caudal basal ganglia control saccades by conveying long-term values (stable values) of many visual objects toward the superior colliculus. In experiment 1, we injected a tracer in the caudate tail (CDt), and found local dense plexuses of axon terminals in the caudal-dorsal-lateral part of substantia nigra pars reticulata (cdlSNr) and the caudal-ventral part of globus pallidus externus (cvGPe). These anterograde projections may correspond to the direct and indirect pathways, respectively. To verify this in experiment 2, we injected different tracers into cdlSNr and cvGPe, and found many retrogradely labeled neurons in CDt and, in addition, the caudal-ventral part of the putamen (cvPut). These cdlSNr-projecting and cvGPe-projecting neurons were found intermingled in both CDt and cvPut (which we call 'striatum tail'). A small but significant proportion of neurons (< 15%) were double-labeled, indicating that they projected to both cdlSNr and cvGPe. These anatomical results suggest that stable value signals (good vs. bad) are sent from the striatum tail to cdlSNr and cvGPe in a biased (but not exclusive) manner. These connections may play an important role in biasing saccades toward higher-valued objects and away from lower-valued objects. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. Exercise Mode Moderates the Relationship Between Mobility and Basal Ganglia Volume in Healthy Older Adults

    PubMed Central

    Nagamatsu, Lindsay S.; Weinstein, Andrea M.; Erickson, Kirk I.; Fanning, Jason; Awick, Elizabeth A.; Kramer, Arthur F.; McAuley, Edward

    2015-01-01

    Background Identifying effective intervention strategies to combat age-related decline in mobility and brain health is a priority. The primary aim of our study was to examine whether 12 months of aerobic training (AT) versus balance and toning (BAT) exercises moderates the relationship between change in mobility and change in basal ganglia volume in older adults. Design Secondary analysis of a randomized controlled trial. Setting Champaign-Urbana, Illinois. Participants Community-dwelling older adults (N = 101; mean age = 66.41 years) Intervention 12-month exercise trial with two groups: AT and BAT. Measurements Mobility was assessed by the Timed Up and Go (TUG) test. Basal ganglia (putamen, caudate nucleus, pallidum) was segmented from T1-weighted MR images using FIRST. Measurements were obtained at baseline and trial completion. Hierarchical multiple regression was conducted to examine whether exercise mode moderates the relationship between change in mobility and change in basal ganglia volume over 12 months. Age, sex, and education were included as covariates. Results Exercise mode significantly moderated the relationship between change in mobility and change in left putamen volume. Specifically, for the AT group, volume of the left putamen did not change, regardless of change in mobility. Similarly, in the BAT group, those who improved their mobility most over 12 months had no change in left putamen volume; however, those who declined in mobility levels significantly decreased in left putamen volume. Conclusion Our primary finding that older adults who engage in 12 months of balance and tone training and improve mobility exhibit maintenance of brain volume in a key region responsible for motor control provides compelling evidence that such exercises can contribute to the promotion of functional independence and healthy aging. PMID:26782858

  10. Nonlinear predictive control for adaptive adjustments of deep brain stimulation parameters in basal ganglia-thalamic network.

    PubMed

    Su, Fei; Wang, Jiang; Niu, Shuangxia; Li, Huiyan; Deng, Bin; Liu, Chen; Wei, Xile

    2018-02-01

    The efficacy of deep brain stimulation (DBS) for Parkinson's disease (PD) depends in part on the post-operative programming of stimulation parameters. Closed-loop stimulation is one method to realize the frequent adjustment of stimulation parameters. This paper introduced the nonlinear predictive control method into the online adjustment of DBS amplitude and frequency. This approach was tested in a computational model of basal ganglia-thalamic network. The autoregressive Volterra model was used to identify the process model based on physiological data. Simulation results illustrated the efficiency of closed-loop stimulation methods (amplitude adjustment and frequency adjustment) in improving the relay reliability of thalamic neurons compared with the PD state. Besides, compared with the 130Hz constant DBS the closed-loop stimulation methods can significantly reduce the energy consumption. Through the analysis of inter-spike-intervals (ISIs) distribution of basal ganglia neurons, the evoked network activity by the closed-loop frequency adjustment stimulation was closer to the normal state. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys

    PubMed Central

    Deffains, Marc; Iskhakova, Liliya; Katabi, Shiran; Haber, Suzanne N; Israel, Zvi; Bergman, Hagai

    2016-01-01

    The striatum and the subthalamic nucleus (STN) constitute the input stage of the basal ganglia (BG) network and together innervate BG downstream structures using GABA and glutamate, respectively. Comparison of the neuronal activity in BG input and downstream structures reveals that subthalamic, not striatal, activity fluctuations correlate with modulations in the increase/decrease discharge balance of BG downstream neurons during temporal discounting classical condition task. After induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), abnormal low beta (8-15 Hz) spiking and local field potential (LFP) oscillations resonate across the BG network. Nevertheless, LFP beta oscillations entrain spiking activity of STN, striatal cholinergic interneurons and BG downstream structures, but do not entrain spiking activity of striatal projection neurons. Our results highlight the pivotal role of STN divergent projections in BG physiology and pathophysiology and may explain why STN is such an effective site for invasive treatment of advanced Parkinson's disease and other BG-related disorders. DOI: http://dx.doi.org/10.7554/eLife.16443.001 PMID:27552049

  12. Airborne copper exposure in school environments associated with poorer motor performance and altered basal ganglia.

    PubMed

    Pujol, Jesus; Fenoll, Raquel; Macià, Dídac; Martínez-Vilavella, Gerard; Alvarez-Pedrerol, Mar; Rivas, Ioar; Forns, Joan; Deus, Joan; Blanco-Hinojo, Laura; Querol, Xavier; Sunyer, Jordi

    2016-06-01

    Children are more vulnerable to the effects of environmental elements. A variety of air pollutants are among the identified factors causing neural damage at toxic concentrations. It is not obvious, however, to what extent the tolerated high levels of air pollutants are able to alter brain development. We have specifically investigated the neurotoxic effects of airborne copper exposure in school environments. Speed and consistency of motor response were assessed in 2836 children aged from 8 to 12 years. Anatomical MRI, diffusion tensor imaging, and functional MRI were used to directly test the brain repercussions in a subgroup of 263 children. Higher copper exposure was associated with poorer motor performance and altered structure of the basal ganglia. Specifically, the architecture of the caudate nucleus region was less complete in terms of both tissue composition and neural track water diffusion. Functional MRI consistently showed a reciprocal connectivity reduction between the caudate nucleus and the frontal cortex. The results establish an association between environmental copper exposure in children and alterations of basal ganglia structure and function.

  13. Convergent evidence for abnormal striatal synaptic plasticity in dystonia

    PubMed Central

    Peterson, David A.; Sejnowski, Terrence J.; Poizner, Howard

    2010-01-01

    Dystonia is a functionally disabling movement disorder characterized by abnormal movements and postures. Although substantial recent progress has been made in identifying genetic factors, the pathophysiology of the disease remains a mystery. A provocative suggestion gaining broader acceptance is that some aspect of neural plasticity may be abnormal. There is also evidence that, at least in some forms of dystonia, sensorimotor “use” may be a contributing factor. Most empirical evidence of abnormal plasticity in dystonia comes from measures of sensorimotor cortical organization and physiology. However, the basal ganglia also play a critical role in sensorimotor function. Furthermore, the basal ganglia are prominently implicated in traditional models of dystonia, are the primary targets of stereotactic neurosurgical interventions, and provide a neural substrate for sensorimotor learning influenced by neuromodulators. Our working hypothesis is that abnormal plasticity in the basal ganglia is a critical link between the etiology and pathophysiology of dystonia. In this review we set up the background for this hypothesis by integrating a large body of disparate indirect evidence that dystonia may involve abnormalities in synaptic plasticity in the striatum. After reviewing evidence implicating the striatum in dystonia, we focus on the influence of two neuromodulatory systems: dopamine and acetylcholine. For both of these neuromodulators, we first describe the evidence for abnormalities in dystonia and then the means by which it may influence striatal synaptic plasticity. Collectively, the evidence suggests that many different forms of dystonia may involve abnormal plasticity in the striatum. An improved understanding of these altered plastic processes would help inform our understanding of the pathophysiology of dystonia, and, given the role of the striatum in sensorimotor learning, provide a principled basis for designing therapies aimed at the dynamic processes

  14. Singing can improve speech function in aphasics associated with intact right basal ganglia and preserve right temporal glucose metabolism: Implications for singing therapy indication.

    PubMed

    Akanuma, Kyoko; Meguro, Kenichi; Satoh, Masayuki; Tashiro, Manabu; Itoh, Masatoshi

    2016-01-01

    Clinically, we know that some aphasic patients can sing well despite their speech disturbances. Herein, we report 10 patients with non-fluent aphasia, of which half of the patients improved their speech function after singing training. We studied ten patients with non-fluent aphasia complaining of difficulty finding words. All had lesions in the left basal ganglia or temporal lobe. They selected the melodies they knew well, but which they could not sing. We made a new lyric with a familiar melody using words they could not name. The singing training using these new lyrics was performed for 30 minutes once a week for 10 weeks. Before and after the training, their speech functions were assessed by language tests. At baseline, 6 of them received positron emission tomography to evaluate glucose metabolism. Five patients exhibited improvements after intervention; all but one exhibited intact right basal ganglia and left temporal lobes, but all exhibited left basal ganglia lesions. Among them, three subjects exhibited preserved glucose metabolism in the right temporal lobe. We considered that patients who exhibit intact right basal ganglia and left temporal lobes, together with preserved right hemispheric glucose metabolism, might be an indication of the effectiveness of singing therapy.

  15. How does environmental enrichment reduce repetitive motor behaviors? Neuronal activation and dendritic morphology in the indirect basal ganglia pathway of a mouse model

    PubMed Central

    Bechard, Allison R.; Cacodcar, Nadia; King, Michael A.; Lewis, Mark H.

    2015-01-01

    Repetitive motor behaviors are observed in many neurodevelopmental and neurological disorders (e.g. autism spectrum disorders, Tourette syndrome, fronto-temporal dementia). Despite their clinical importance, the neurobiology underlying these highly stereotyped, apparently functionless behaviors is poorly understood. Identification of mechanisms that mediate the development of repetitive behaviors will aid in the discovery of new therapeutic targets and treatment development. Using a deer mouse model, we have shown that decreased indirect basal ganglia pathway activity is associated with high levels of repetitive behavior. Environmental enrichment (EE) markedly attenuates the development of such aberrant behaviors in mice, although mechanisms driving this effect are unknown. We hypothesized that EE would reduce repetitive motor behaviors by increasing indirect basal ganglia pathway function. We assessed neuronal activation and dendritic spine density in basal ganglia of adult deer mice reared in EE and standard housing. Significant increases in neuronal activation and dendritic spine densities were observed only in the subthalamic nucleus (STN) and globus pallidus (GP), and only for those mice that exhibited an EE-induced decrease in repetitive motor behavior. As the STN and GP lie within the indirect pathway, these data suggest that EE-induced attenuation of repetitive motor behaviors is associated with increased functional activation of the indirect basal ganglia pathway. These results are consistent with our other findings highlighting the importance of the indirect pathway in mediating repetitive motor behaviors. PMID:26620495

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

    PubMed

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

    2017-11-01

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

  17. Focal expression of mutant huntingtin in the songbird basal ganglia disrupts cortico-basal ganglia networks and vocal sequences

    PubMed Central

    Tanaka, Masashi; Singh Alvarado, Jonnathan; Murugan, Malavika; Mooney, Richard

    2016-01-01

    The basal ganglia (BG) promote complex sequential movements by helping to select elementary motor gestures appropriate to a given behavioral context. Indeed, Huntington’s disease (HD), which causes striatal atrophy in the BG, is characterized by hyperkinesia and chorea. How striatal cell loss alters activity in the BG and downstream motor cortical regions to cause these disorganized movements remains unknown. Here, we show that expressing the genetic mutation that causes HD in a song-related region of the songbird BG destabilizes syllable sequences and increases overall vocal activity, but leave the structure of individual syllables intact. These behavioral changes are paralleled by the selective loss of striatal neurons and reduction of inhibitory synapses on pallidal neurons that serve as the BG output. Chronic recordings in singing birds revealed disrupted temporal patterns of activity in pallidal neurons and downstream cortical neurons. Moreover, reversible inactivation of the cortical neurons rescued the disorganized vocal sequences in transfected birds. These findings shed light on a key role of temporal patterns of cortico-BG activity in the regulation of complex motor sequences and show how a genetic mutation alters cortico-BG networks to cause disorganized movements. PMID:26951661

  18. Characterization of multifocal T2*-weighted MRI hypointensities in the basal ganglia of elderly, community-dwelling subjects☆

    PubMed Central

    Glatz, Andreas; Valdés Hernández, Maria C.; Kiker, Alexander J.; Bastin, Mark E.; Deary, Ian J.; Wardlaw, Joanna M.

    2013-01-01

    Multifocal T2*-weighted (T2*w) hypointensities in the basal ganglia, which are believed to arise predominantly from mineralized small vessels and perivascular spaces, have been proposed as a biomarker for cerebral small vessel disease. This study provides baseline data on their appearance on conventional structural MRI for improving and automating current manual segmentation methods. Using a published thresholding method, multifocal T2*w hypointensities were manually segmented from whole brain T2*w volumes acquired from 98 community-dwelling subjects in their early 70s. Connected component analysis was used to derive the average T2*w hypointensity count and load per basal ganglia nucleus, as well as the morphology of their connected components, while nonlinear spatial probability mapping yielded their spatial distribution. T1-weighted (T1w), T2-weighted (T2w) and T2*w intensity distributions of basal ganglia T2*w hypointensities and their appearance on T1w and T2w MRI were investigated to gain further insights into the underlying tissue composition. In 75/98 subjects, on average, 3 T2*w hypointensities with a median total volume per intracranial volume of 50.3 ppm were located in and around the globus pallidus. Individual hypointensities appeared smooth and spherical with a median volume of 12 mm3 and median in-plane area of 4 mm2. Spatial probability maps suggested an association between T2*w hypointensities and the point of entry of lenticulostriate arterioles into the brain parenchyma. T1w and T2w and especially the T2*w intensity distributions of these hypointensities, which were negatively skewed, were generally not normally distributed indicating an underlying inhomogeneous tissue structure. Globus pallidus T2*w hypointensities tended to appear hypo- and isointense on T1w and T2w MRI, whereas those from other structures appeared iso- and hypointense. This pattern could be explained by an increased mineralization of the globus pallidus. In conclusion, the

  19. Deletion of the Ttf1 gene in differentiated neurons disrupts female reproduction without impairing basal ganglia function.

    PubMed

    Mastronardi, Claudio; Smiley, Gregory G; Raber, Jacob; Kusakabe, Takashi; Kawaguchi, Akio; Matagne, Valerie; Dietzel, Anja; Heger, Sabine; Mungenast, Alison E; Cabrera, Ricardo; Kimura, Shioko; Ojeda, Sergio R

    2006-12-20

    Thyroid transcription factor 1 (TTF1) [also known as Nkx2.1 (related to the NK-2 class of homeobox genes) and T/ebp (thyroid-specific enhancer-binding protein)], a homeodomain gene required for basal forebrain morphogenesis, remains expressed in the hypothalamus after birth, suggesting a role in neuroendocrine function. Here, we show an involvement of TTF1 in the control of mammalian puberty and adult reproductive function. Gene expression profiling of the nonhuman primate hypothalamus revealed that TTF1 expression increases at puberty. Mice in which the Ttf1 gene was ablated from differentiated neurons grew normally and had normal basal ganglia/hypothalamic morphology but exhibited delayed puberty, reduced reproductive capacity, and a short reproductive span. These defects were associated with reduced hypothalamic expression of genes required for sexual development and deregulation of a gene involved in restraining puberty. No extrapyramidal impairments associated with basal ganglia dysfunction were apparent. Thus, although TTF1 appears to fulfill only a morphogenic function in the ventral telencephalon, once this function is satisfied in the hypothalamus, TTF1 remains active as part of the transcriptional machinery controlling female sexual development.

  20. Rehabilitation program based on sensorimotor recovery improves the static and dynamic balance and modifies the basal ganglia neurochemistry

    PubMed Central

    Delli Pizzi, Stefano; Bellomo, Rosa Grazia; Carmignano, Simona Maria; Ancona, Emilio; Franciotti, Raffaella; Supplizi, Marco; Barassi, Giovanni; Onofrj, Marco; Bonanni, Laura; Saggini, Raoul

    2017-01-01

    Abstract Rehabilitation interventions represent an alternative strategy to pharmacological treatment in order to slow or reverse some functional aspects of disability in Parkinson's disease (PD). To date, the neurophysiological mechanisms underlying rehabilitation-mediated improvement in PD patients are still poorly understood. Interestingly, growing evidence has highlighted a key role of the glutamate in neurogenesis and brain plasticity. The brain levels of glutamate, and of its precursor glutamine, can be detected in vivo and noninvasively as “Glx” by means of proton magnetic resonance spectroscopy (1H-MRS). In the present pilot study, 7 PD patients with frequent falls and axial dystonia underwent 8-week rehabilitative protocol focused on sensorimotor improvement. Clinical evaluation and Glx quantification were performed before and after rehabilitation. The Glx assessment was focused on the basal ganglia in agreement with their key role in the motor functions. We found that the rehabilitation program improves the static and dynamic balance in PD patients, promoting a better global motor performance. Moreover, we observed that the levels of Glx within the left basal ganglia were higher after rehabilitation as compared with baseline. Thus, we posit that our sensorimotor rehabilitative protocol could stimulate the glutamate metabolism in basal ganglia and, in turn, neuroplasticity processes. We also hypothesize that these mechanisms could prepare the ground to restore the functional interaction among brain areas deputed to motor controls, which are affected in PD. PMID:29390267

  1. A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease.

    PubMed

    Bardinet, Eric; Bhattacharjee, Manik; Dormont, Didier; Pidoux, Bernard; Malandain, Grégoire; Schüpbach, Michael; Ayache, Nicholas; Cornu, Philippe; Agid, Yves; Yelnik, Jérôme

    2009-02-01

    The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.

  2. Basal ganglia calcification as a putative cause for cognitive decline.

    PubMed

    de Oliveira, João Ricardo Mendes; de Oliveira, Matheus Fernandes

    2013-01-01

    Basal ganglia calcifications (BGC) may be present in various medical conditions, such as infections, metabolic, psychiatric and neurological diseases, associated with different etiologies and clinical outcomes, including parkinsonism, psychosis, mood swings and dementia. A literature review was performed highlighting the main neuropsychological findings of BGC, with particular attention to clinical reports of cognitive decline. Neuroimaging studies combined with neuropsychological analysis show that some patients have shown progressive disturbances of selective attention, declarative memory and verbal perseveration. Therefore, the calcification process might represent a putative cause for dementia syndromes, suggesting a probable link among calcinosis, the aging process and eventually with neuronal death. The increasing number of reports available will foster a necessary discussion about cerebral calcinosis and its role in determining symptomatology in dementia patients.

  3. Basal Ganglia Activity Mirrors a Benefit of Action and Reward on Long-Lasting Event Memory.

    PubMed

    Koster, Raphael; Guitart-Masip, Marc; Dolan, Raymond J; Düzel, Emrah

    2015-12-01

    The expectation of reward is known to enhance a consolidation of long-term memory for events. We tested whether this effect is driven by positive valence or action requirements tied to expected reward. Using a functional magnetic resonance imaging (fMRI) paradigm in young adults, novel images predicted gain or loss outcomes, which in turn were either obtained or avoided by action or inaction. After 24 h, memory for these images reflected a benefit of action as well as a congruence of action requirements and valence, namely, action for reward and inaction for avoidance. fMRI responses in the hippocampus, a region known to be critical for long-term memory function, reflected the anticipation of inaction. In contrast, activity in the putamen mirrored the congruence of action requirement and valence, whereas other basal ganglia regions mirrored overall action benefits on long-lasting memory. The findings indicate a novel type of functional division between the hippocampus and the basal ganglia in the motivational regulation of long-term memory consolidation, which favors remembering events that are worth acting for. © The Author 2015. Published by Oxford University Press.

  4. Neurotensin receptor binding levels in basal ganglia are not altered in Huntington's chorea or schizophrenia

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

    Palacios, J.M.; Chinaglia, G.; Rigo, M.

    1991-02-01

    Autoradiographic techniques were used to examine the distribution and levels of neurotensin receptor binding sites in the basal ganglia and related regions of the human brain. Monoiodo ({sup 125}I-Tyr3)neurotensin was used as a ligand. High amounts of neurotensin receptor binding sites were found in the substantia nigra pars compacta. Lower but significant quantities of neurotensin receptor binding sites characterized the caudate, putamen, and nucleus accumbens, while very low quantities were seen in both medial and lateral segments of the globus pallidus. In Huntington's chorea, the levels of neurotensin receptor binding sites were found to be comparable to those of controlmore » cases. Only slight but not statistically significant decreases in amounts of receptor binding sites were detected in the dorsal part of the head and in the body of caudate nucleus. No alterations in the levels of neurotensin receptor binding sites were observed in the substantia nigra pars compacta and reticulata. These results suggest that a large proportion of neurotensin receptor binding sites in the basal ganglia are located on intrinsic neurons and on extrinsic afferent fibers that do not degenerate in Huntington's disease.« less

  5. Endoscopic Evacuation of Basal Ganglia Hematoma: Surgical Technique, Outcome, and Learning Curve.

    PubMed

    Ma, Lichao; Hou, Yuanzheng; Zhu, Ruyuan; Chen, Xiaolei

    2017-05-01

    Minimally invasive endoscopic hematoma evacuation is a promising treatment option for intracerebral hemorrhage. However, the technique still needs improvement. We report our clinical experience of using this technique to evacuate deep-seated basal ganglia hematomas. The frontal approach was used in most patients. The preoperative and postoperative hematoma volumes, Glasgow Coma Scale, hematoma evacuation rate, 30-day mortality, and long-term outcome defined by the modified Rankin Scale were analyzed retrospectively. The surgical duration per milliliter of clot (DPM) was calculated. The learning curve for this technique was determined based on the relation between the DPM and evacuation rate per the number of cases experienced. A total of 24 patients were enrolled. The evacuation rate was 87% ± 10%. The average Glasgow Coma Scale score recovered from 8 to 13 after surgery. Twenty-one patients had follow-up data. The follow-up time was 13 ± 6 months. The 30-day mortality after surgery was zero. Forty-eight percent of patients (10/21) achieved a favorable outcome. The DPM (P = 0.92) and evacuation rate (P = 0.64) did not change substantially with the number of cases experienced. Endoscopic port surgery for hematoma evacuation via the frontal approach is a safe surgical option for deep-seated basal ganglia hematomas. This technique is minimally invasive and may be helpful to provide better long-term outcomes for selected patients. For neurosurgeons, the learning curve for this technique is steep, which implies that the skills needed for our technique can be easily acquired. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Magnetic Susceptibility Changes in the Basal Ganglia and Brain Stem of Patients with Wilson's Disease: Evaluation with Quantitative Susceptibility Mapping.

    PubMed

    Doganay, Selim; Gumus, Kazim; Koc, Gonca; Bayram, Ayse Kacar; Dogan, Mehmet Sait; Arslan, Duran; Gumus, Hakan; Gorkem, Sureyya Burcu; Ciraci, Saliha; Serin, Halil Ibrahim; Coskun, Abdulhakim

    2018-01-10

    Wilson's disease (WD) is characterized with the accumulation of copper in the liver and brain. The objective of this study is to quantitatively measure the susceptibility changes of basal ganglia and brain stem of pediatric patients with neurological WD using quantitative susceptibility mapping (QSM) in comparison to healthy controls. Eleven patients with neurological WD (mean age 15 ± 3.3 years, range 10-22 years) and 14 agematched controls were prospectively recruited. Both groups were scanned on a 1.5 Tesla clinical scanner. In addition to T 1 - and T 2 -weighted MR images, a 3D multi-echo spoiled gradient echo (GRE) sequence was acquired and QSM images were derived offline. The quantitative measurement of susceptibility of corpus striatum, thalamus of each hemisphere, midbrain, and pons were assessed with the region of interest analysis on the QSM images. The susceptibility values for the patient and control groups were compared using twosample t-test. One patient with WD had T 1 shortening in the bilateral globus pallidus. Another one had hyperintensity in the bilateral putamen, caudate nuclei, and substantia nigra on T 2 -weighted images. The rest of the patients with WD and all subjects of the control group had no signal abnormalities on conventional MR images. The susceptibility measures of right side of globus pallidus, putamen, thalamus, midbrain, and entire pons were significantly different in patients compared to controls (P < 0.05). QSM method exhibits increased susceptibility differences of basal ganglia and brain stem in patients with WD that have neurologic impairment even if no signal alteration is detected on T 1 - and T 2 -weighted MR images.

  7. Neuromodulatory adaptive combination of correlation-based learning in cerebellum and reward-based learning in basal ganglia for goal-directed behavior control

    PubMed Central

    Dasgupta, Sakyasingha; Wörgötter, Florentin; Manoonpong, Poramate

    2014-01-01

    Goal-directed decision making in biological systems is broadly based on associations between conditional and unconditional stimuli. This can be further classified as classical conditioning (correlation-based learning) and operant conditioning (reward-based learning). A number of computational and experimental studies have well established the role of the basal ganglia in reward-based learning, where as the cerebellum plays an important role in developing specific conditioned responses. Although viewed as distinct learning systems, recent animal experiments point toward their complementary role in behavioral learning, and also show the existence of substantial two-way communication between these two brain structures. Based on this notion of co-operative learning, in this paper we hypothesize that the basal ganglia and cerebellar learning systems work in parallel and interact with each other. We envision that such an interaction is influenced by reward modulated heterosynaptic plasticity (RMHP) rule at the thalamus, guiding the overall goal directed behavior. Using a recurrent neural network actor-critic model of the basal ganglia and a feed-forward correlation-based learning model of the cerebellum, we demonstrate that the RMHP rule can effectively balance the outcomes of the two learning systems. This is tested using simulated environments of increasing complexity with a four-wheeled robot in a foraging task in both static and dynamic configurations. Although modeled with a simplified level of biological abstraction, we clearly demonstrate that such a RMHP induced combinatorial learning mechanism, leads to stabler and faster learning of goal-directed behaviors, in comparison to the individual systems. Thus, in this paper we provide a computational model for adaptive combination of the basal ganglia and cerebellum learning systems by way of neuromodulated plasticity for goal-directed decision making in biological and bio-mimetic organisms. PMID:25389391

  8. Neuromodulatory adaptive combination of correlation-based learning in cerebellum and reward-based learning in basal ganglia for goal-directed behavior control.

    PubMed

    Dasgupta, Sakyasingha; Wörgötter, Florentin; Manoonpong, Poramate

    2014-01-01

    Goal-directed decision making in biological systems is broadly based on associations between conditional and unconditional stimuli. This can be further classified as classical conditioning (correlation-based learning) and operant conditioning (reward-based learning). A number of computational and experimental studies have well established the role of the basal ganglia in reward-based learning, where as the cerebellum plays an important role in developing specific conditioned responses. Although viewed as distinct learning systems, recent animal experiments point toward their complementary role in behavioral learning, and also show the existence of substantial two-way communication between these two brain structures. Based on this notion of co-operative learning, in this paper we hypothesize that the basal ganglia and cerebellar learning systems work in parallel and interact with each other. We envision that such an interaction is influenced by reward modulated heterosynaptic plasticity (RMHP) rule at the thalamus, guiding the overall goal directed behavior. Using a recurrent neural network actor-critic model of the basal ganglia and a feed-forward correlation-based learning model of the cerebellum, we demonstrate that the RMHP rule can effectively balance the outcomes of the two learning systems. This is tested using simulated environments of increasing complexity with a four-wheeled robot in a foraging task in both static and dynamic configurations. Although modeled with a simplified level of biological abstraction, we clearly demonstrate that such a RMHP induced combinatorial learning mechanism, leads to stabler and faster learning of goal-directed behaviors, in comparison to the individual systems. Thus, in this paper we provide a computational model for adaptive combination of the basal ganglia and cerebellum learning systems by way of neuromodulated plasticity for goal-directed decision making in biological and bio-mimetic organisms.

  9. Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy.

    PubMed

    Welter, M-L; Burbaud, P; Fernandez-Vidal, S; Bardinet, E; Coste, J; Piallat, B; Borg, M; Besnard, S; Sauleau, P; Devaux, B; Pidoux, B; Chaynes, P; Tézenas du Montcel, S; Bastian, A; Langbour, N; Teillant, A; Haynes, W; Yelnik, J; Karachi, C; Mallet, L

    2011-05-03

    Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive-compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1-8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative-limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative-limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology.

  10. Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy.

    PubMed

    Silverman, Daniel H S; Dy, Christine J; Castellon, Steven A; Lai, Jasmine; Pio, Betty S; Abraham, Laura; Waddell, Kari; Petersen, Laura; Phelps, Michael E; Ganz, Patricia A

    2007-07-01

    To explore the relationship of regional cerebral blood flow and metabolism with cognitive function and past exposure to chemotherapy for breast cancer. Subjects treated for breast cancer with adjuvant chemotherapy remotely (5-10 years previously) were studied with neuropsychologic testing and positron emission tomography (PET), and were compared with control subjects who had never received chemotherapy. [O-15] water PET scans was acquired during performance of control and memory-related tasks to evaluate cognition-related cerebral blood flow, and [F-18] fluorodeoxyglucose (FDG) PET scans were acquired to evaluate resting cerebral metabolism. PET scans were analyzed by statistical parametric mapping and region of interest methods of analysis. During performance of a short-term recall task, modulation of cerebral blood flow in specific regions of frontal cortex and cerebellum was significantly altered in chemotherapy-treated subjects. Cerebral activation in chemotherapy-treated subjects differed most significantly from untreated subjects in inferior frontal gyrus, and resting metabolism in this area correlated with performance on a short-term memory task previously found to be particularly impaired in chemotherapy-treated subjects. In examining drug-class specific effects, metabolism of the basal ganglia was significantly decreased in tamoxifen + chemotherapy-treated patients compared with chemotherapy-only breast cancer subjects or with subjects who had not received chemotherapy, while chemotherapy alone was not associated with decreased basal ganglia activity relative to untreated subjects. Specific alterations in activity of frontal cortex, cerebellum, and basal ganglia in breast cancer survivors were documented by functional neuroimaging 5-10 years after completion of chemotherapy.

  11. Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

    PubMed

    Maurice, Nicolas; Deltheil, Thierry; Melon, Christophe; Degos, Bertrand; Mourre, Christiane; Amalric, Marianne; Kerkerian-Le Goff, Lydia

    2015-01-01

    Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson's disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease.

  12. Total numbers of neurons and glial cells in cortex and basal ganglia of aged brains with Down syndrome--a stereological study.

    PubMed

    Karlsen, Anna Schou; Pakkenberg, Bente

    2011-11-01

    The total numbers of neurons and glial cells in the neocortex and basal ganglia in adults with Down syndrome (DS) were estimated with design-based stereological methods, providing quantitative data on brains affected by delayed development and accelerated aging. Cell numbers, volume of regions, and densities of neurons and glial cell subtypes were estimated in brains from 4 female DS subjects (mean age 66 years) and 6 female controls (mean age 70 years). The DS subjects were estimated to have about 40% fewer neocortical neurons in total (11.1 × 10(9) vs. 17.8 × 10(9), 2p ≤ 0.001) and almost 30% fewer neocortical glial cells with no overlap to controls (12.8 × 10(9) vs. 18.2 × 10(9), 2p = 0.004). In contrast, the total number of neurons in the basal ganglia was the same in the 2 groups, whereas the number of oligodendrocytes in the basal ganglia was reduced by almost 50% in DS (405 × 10(6) vs. 816 × 10(6), 2p = 0.01). We conclude that trisomy 21 affects cortical structures more than central gray matter emphasizing the differential impairment of brain development. Despite concomitant Alzheimer-like pathology, the neurodegenerative outcome in a DS brain deviates from common Alzheimer disease.

  13. The impact of multichannel microelectrode recording (MER) in deep brain stimulation of the basal ganglia.

    PubMed

    Kinfe, Thomas M; Vesper, Jan

    2013-01-01

    Deep brain stimulation (DBS) of the basal ganglia (Ncl. subthalamicus, Ncl. ventralis intermedius thalami, globus pallidus internus) has become an evidence-based and well-established treatment option in otherwise refractory movement disorders. The Ncl. subthalamicus (STN) is the target of choice in Parkinson's disease.However, a considerable discussion is currently ongoing with regard to the necessity for micro-electrode recording (MER) in DBS surgery.The present review provides an overview on deep brain stimulation and (MER) of the STN in patients with Parkinson's disease. Detailed description is given concerning the multichannel MER systems nowadays available for DBS of the basal ganglia, especially of the STN, as a useful tool for target refinement. Furthermore, an overview is given of the historical aspects, spatial mapping of the STN by MER, and its impact for accuracy and precision in current functional stereotactic neurosurgery.The pros concerning target refinement by MER means on the one hand, and cons including increased bleeding risk, increased operation time, local or general anesthesia, and single versus multichannel microelectrode recording are discussed in detail. Finally, the authors favor the use of MER with intraoperative testing combined with imaging to achieve a more precise electrode placement, aiming to ameliorate clinical outcome in therapy-resistant movement disorders.

  14. Basal Ganglia Contributions to Motor Control: A Vigorous Tutor

    PubMed Central

    Turner, Robert S.; Desmurget, Michel

    2010-01-01

    SUMMARY OF RECENT ADVANCES The roles of the basal ganglia (BG) in motor control are much debated. Many influential hypotheses have grown from studies in which output signals of the BG were not blocked, but pathologically-disturbed. A weakness of that approach is that the resulting behavioral impairments reflect degraded function of the BG per se mixed together with secondary dysfunctions of BG-recipient brain areas. To overcome that limitation, several studies have focused on the main skeletomotor output region of the BG, the globus pallidus internus (GPi). Using single-cell recording and inactivation protocols these studies provide consistent support for two hypotheses: the BG modulates movement performance (“vigor”) according to motivational factors (i.e., context-specific cost/reward functions) and the BG contributes to motor learning. Results from these studies also add to the problems that confront theories positing that the BG selects movement, inhibits unwanted motor responses, corrects errors online, or stores and produces well-learned motor skills. PMID:20850966

  15. Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson’s Disease

    PubMed Central

    Maurice, Nicolas; Deltheil, Thierry; Melon, Christophe; Degos, Bertrand; Mourre, Christiane

    2015-01-01

    Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson’s disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease. PMID:26571268

  16. Measurement of Lactate Content and Amide Proton Transfer Values in the Basal Ganglia of a Neonatal Piglet Hypoxic-Ischemic Brain Injury Model Using MRI.

    PubMed

    Zheng, Y; Wang, X-M

    2017-04-01

    As amide proton transfer imaging is sensitive to protein content and intracellular pH, it has been widely used in the nervous system, including brain tumors and stroke. This work aimed to measure the lactate content and amide proton transfer values in the basal ganglia of a neonatal piglet hypoxic-ischemic brain injury model by using MR spectroscopy and amide proton transfer imaging. From 58 healthy neonatal piglets (3-5 days after birth; weight, 1-1.5 kg) selected initially, 9 piglets remained in the control group and 43 piglets, in the hypoxic-ischemic brain injury group. Single-section amide proton transfer imaging was performed at the coronal level of the basal ganglia. Amide proton transfer values of the bilateral basal ganglia were measured in all piglets. The ROI of MR spectroscopy imaging was the right basal ganglia, and the postprocessing was completed with LCModel software. After hypoxic-ischemic insult, the amide proton transfer values immediately decreased, and at 0-2 hours, they remained at their lowest level. Thereafter, they gradually increased and finally exceeded those of the control group at 48-72 hours. After hypoxic-ischemic insult, the lactate content increased immediately, was maximal at 2-6 hours, and then gradually decreased to the level of the control group. The amide proton transfer values were negatively correlated with lactate content ( r = -0.79, P < .05). This observation suggests that after hypoxic-ischemic insult, the recovery of pH was faster than that of lactate homeostasis. © 2017 by American Journal of Neuroradiology.

  17. Basal ganglia, thalamus and neocortical atrophy predicting slowed cognitive processing in multiple sclerosis.

    PubMed

    Batista, Sonia; Zivadinov, Robert; Hoogs, Marietta; Bergsland, Niels; Heininen-Brown, Mari; Dwyer, Michael G; Weinstock-Guttman, Bianca; Benedict, Ralph H B

    2012-01-01

    Information-processing speed (IPS) slowing is a primary cognitive deficit in multiple sclerosis (MS). Basal ganglia, thalamus and neocortex are thought to have a key role for efficient information-processing, yet the specific relative contribution of these structures for MS-related IPS impairment is poorly understood. To determine if basal ganglia and thalamus atrophy independently contribute to visual and auditory IPS impairment in MS, after controlling for the influence of neocortical volume, we enrolled 86 consecutive MS patients and 25 normal controls undergoing 3T brain MRI and neuropsychological testing. Using Sienax and FIRST software, neocortical and deep gray matter (DGM) volumes were calculated. Neuropsychological testing contributed measures of auditory and visual IPS using the Paced Auditory Serial Addition Test (PASAT) and the Symbol Digit Modalities Test (SDMT), respectively. MS patients exhibited significantly slower IPS relative to controls and showed reduction in neocortex, caudate, putamen, globus pallidus, thalamus and nucleus accumbens volume. SDMT and PASAT were significantly correlated with all DGM regions. These effects were mitigated by controlling for the effects of neocortical volume, but all DGM volumes remained significantly correlated with SDMT, putamen (r = 0.409, p < 0.001) and thalamus (r = 0.362, p < 0.001) having the strongest effects, whereas for PASAT, the correlation was significant for putamen (r = 0.313, p < 0.01) but not for thalamus. We confirm the significant role of thalamus atrophy in MS-related IPS slowing and find that putamen atrophy is also a significant contributor to this disorder. These DGM structures have independent, significant roles, after controlling for the influence of neocortex atrophy.

  18. Basal Ganglia, Dopamine and Temporal Processing: Performance on Three Timing Tasks on and off Medication in Parkinson's Disease

    ERIC Educational Resources Information Center

    Jones, Catherine R. G.; Malone, Tim J. L.; Dirnberger, Georg; Edwards, Mark; Jahanshahi, Marjan

    2008-01-01

    A pervasive hypothesis in the timing literature is that temporal processing in the milliseconds and seconds range engages the basal ganglia and is modulated by dopamine. This hypothesis was investigated by testing 12 patients with Parkinson's disease (PD), both "on" and "off" dopaminergic medication, and 20 healthy controls on three timing tasks.…

  19. Eyeblink Conditioning Deficits Indicate Timing and Cerebellar Abnormalities in Schizophrenia

    ERIC Educational Resources Information Center

    Brown, S.M.; Kieffaber, P.D.; Carroll, C.A.; Vohs, J.L.; Tracy, J.A.; Shekhar, A.; O'Donnell, B.F.; Steinmetz, J.E.; Hetrick, W.P.

    2005-01-01

    Accumulating evidence indicates that individuals with schizophrenia manifest abnormalities in structures (cerebellum and basal ganglia) and neurotransmitter systems (dopamine) linked to internal-timing processes. A single-cue tone delay eyeblink conditioning paradigm comprised of 100 learning and 50 extinction trials was used to examine cerebellar…

  20. Neural code alterations and abnormal time patterns in Parkinson’s disease

    NASA Astrophysics Data System (ADS)

    Andres, Daniela Sabrina; Cerquetti, Daniel; Merello, Marcelo

    2015-04-01

    Objective. The neural code used by the basal ganglia is a current question in neuroscience, relevant for the understanding of the pathophysiology of Parkinson’s disease. While a rate code is known to participate in the communication between the basal ganglia and the motor thalamus/cortex, different lines of evidence have also favored the presence of complex time patterns in the discharge of the basal ganglia. To gain insight into the way the basal ganglia code information, we studied the activity of the globus pallidus pars interna (GPi), an output node of the circuit. Approach. We implemented the 6-hydroxydopamine model of Parkinsonism in Sprague-Dawley rats, and recorded the spontaneous discharge of single GPi neurons, in head-restrained conditions at full alertness. Analyzing the temporal structure function, we looked for characteristic scales in the neuronal discharge of the GPi. Main results. At a low-scale, we observed the presence of dynamic processes, which allow the transmission of time patterns. Conversely, at a middle-scale, stochastic processes force the use of a rate code. Regarding the time patterns transmitted, we measured the word length and found that it is increased in Parkinson’s disease. Furthermore, it showed a positive correlation with the frequency of discharge, indicating that an exacerbation of this abnormal time pattern length can be expected, as the dopamine depletion progresses. Significance. We conclude that a rate code and a time pattern code can co-exist in the basal ganglia at different temporal scales. However, their normal balance is progressively altered and replaced by pathological time patterns in Parkinson’s disease.

  1. Learning to Select Actions with Spiking Neurons in the Basal Ganglia

    PubMed Central

    Stewart, Terrence C.; Bekolay, Trevor; Eliasmith, Chris

    2012-01-01

    We expand our existing spiking neuron model of decision making in the cortex and basal ganglia to include local learning on the synaptic connections between the cortex and striatum, modulated by a dopaminergic reward signal. We then compare this model to animal data in the bandit task, which is used to test rodent learning in conditions involving forced choice under rewards. Our results indicate a good match in terms of both behavioral learning results and spike patterns in the ventral striatum. The model successfully generalizes to learning the utilities of multiple actions, and can learn to choose different actions in different states. The purpose of our model is to provide both high-level behavioral predictions and low-level spike timing predictions while respecting known neurophysiology and neuroanatomy. PMID:22319465

  2. Basal ganglia systems in ritualistic social displays: reptiles and humans; function and illness.

    PubMed

    Baxter, Lewis R

    2003-08-01

    Complex, situation-specific territorial maintenance routines are similar across living terrestrial vertebrates (=amniotes). Decades ago, Paul MacLean et al., at the Laboratory of Brain Evolution and Behavior of the National Institute of Mental Health, postulated that these are evolutionarily conserved behaviors whose expression is mediated by the similarly conserved amniote basal ganglia and related brain systems (BG systems). Therefore, they undertook studies in nonhuman primates and in small social lizards (the common green anole, Anolis carolinensis) to examine this idea. MacLean et al. also postulated that when BG systems misfunction in humans, behavioral abnormalities result, some of them under the rubric of psychiatric illnesses. Obsessive-compulsive disorder (OCD) was singled out as one likely candidate. In the last dozen years, functional brain imaging studies of OCD patients have validated the contention that this is, in fact, a condition involving dysfunctioning BG systems. Inspired by the MacLean group's original investigations, my colleagues and I have now applied related functional imaging techniques in naturalistic experiments using Anolis to better understand BG systems' roles in the mediation of complex behavioral routines in healthy amniotes. Here, I will review this functional imaging work in primates (man, and a little in monkey) and in lizards. I believe the literature not only supports MacLean et al.'s contentions about BG systems and behavior in general, but also validates Paul MacLean's life-long contention that human behavioral medicine can profit from a broad comparative approach.

  3. Parsing the roles of the frontal lobes and basal ganglia in task control using multivoxel pattern analysis

    PubMed Central

    Kehagia, Angie A.; Ye, Rong; Joyce, Dan W.; Doyle, Orla M.; Rowe, James B.; Robbins, Trevor W.

    2017-01-01

    Cognitive control has traditionally been associated with the prefrontal cortex, based on observations of deficits in patients with frontal lesions. However, evidence from patients with Parkinson’s disease (PD) indicates that subcortical regions also contribute to control under certain conditions. We scanned 17 healthy volunteers while they performed a task switching paradigm that previously dissociated performance deficits arising from frontal lesions in comparison with PD, as a function of the abstraction of the rules that are switched. From a multivoxel pattern analysis by Gaussian Process Classification (GPC), we then estimated the forward (generative) model to infer regional patterns of activity that predict Switch / Repeat behaviour between rule conditions. At 1000 permutations, Switch / Repeat classification accuracy for concrete rules was significant in the basal ganglia, but at chance in the frontal lobe. The inverse pattern was obtained for abstract rules, whereby the conditions were successfully discriminated in the frontal lobe but not in the basal ganglia. This double dissociation highlights the difference between cortical and subcortical contributions to cognitive control and demonstrates the utility of multivariate approaches in investigations of functions that rely on distributed and overlapping neural substrates. PMID:28387585

  4. Influence of basal ganglia on upper limb locomotor synergies. Evidence from deep brain stimulation and L-DOPA treatment in Parkinson's disease.

    PubMed

    Crenna, P; Carpinella, I; Lopiano, L; Marzegan, A; Rabuffetti, M; Rizzone, M; Lanotte, M; Ferrarin, M

    2008-12-01

    Clinical evidence of impaired arm swing while walking in patients with Parkinson's disease suggests that basal ganglia and related systems play an important part in the control of upper limb locomotor automatism. To gain more information on this supraspinal influence, we measured arm and thigh kinematics during walking in 10 Parkinson's disease patients, under four conditions: (i) baseline (no treatment), (ii) therapeutic stimulation of the subthalamic nucleus (STN), (iii)L-DOPA medication and (iv) combined STN stimulation and L-DOPA. Ten age-matched controls provided reference data. Under baseline conditions the range of patients' arm motion was severely restricted, with no correlation with the excursion of the thigh. In addition, the arm swing was abnormally coupled in time with oscillation of the ipsilateral thigh. STN stimulation significantly increased the gait speed and improved the spatio-temporal parameters of arm and thigh motion. The kinematic changes as a function of gait speed changes, however, were significantly smaller for the upper than the lower limb, in contrast to healthy controls. Arm motion was also less responsive after L-DOPA. Simultaneous deep brain stimulation and L-DOPA had additive effects on thigh motion, but not on arm motion and arm-thigh coupling. The evidence that locomotor automatisms of the upper and lower limbs display uncorrelated impairment upon dysfunction of the basal ganglia, as well as different susceptibility to electrophysiological and pharmacological interventions, points to the presence of heterogeneously distributed, possibly partially independent, supraspinal control channels, whereby STN and dopaminergic systems have relatively weaker influence on the executive structures involved in the arm swing and preferential action on those for lower limb movements. These findings might be considered in the light of phylogenetic changes in supraspinal control of limb motion related to primate bipedalism.

  5. Common Features of Neural Activity during Singing and Sleep Periods in a Basal Ganglia Nucleus Critical for Vocal Learning in a Juvenile Songbird

    PubMed Central

    Yanagihara, Shin; Hessler, Neal A.

    2011-01-01

    Reactivations of waking experiences during sleep have been considered fundamental neural processes for memory consolidation. In songbirds, evidence suggests the importance of sleep-related neuronal activity in song system motor pathway nuclei for both juvenile vocal learning and maintenance of adult song. Like those in singing motor nuclei, neurons in the basal ganglia nucleus Area X, part of the basal ganglia-thalamocortical circuit essential for vocal plasticity, exhibit singing-related activity. It is unclear, however, whether Area X neurons show any distinctive spiking activity during sleep similar to that during singing. Here we demonstrate that, during sleep, Area X pallidal neurons exhibit phasic spiking activity, which shares some firing properties with activity during singing. Shorter interspike intervals that almost exclusively occurred during singing in awake periods were also observed during sleep. The level of firing variability was consistently higher during singing and sleep than during awake non-singing states. Moreover, deceleration of firing rate, which is considered to be an important firing property for transmitting signals from Area X to the thalamic nucleus DLM, was observed mainly during sleep as well as during singing. These results suggest that songbird basal ganglia circuitry may be involved in the off-line processing potentially critical for vocal learning during sensorimotor learning phase. PMID:21991379

  6. Altered cortico-basal ganglia motor pathways reflect reduced volitional motor activity in schizophrenia.

    PubMed

    Bracht, Tobias; Schnell, Susanne; Federspiel, Andrea; Razavi, Nadja; Horn, Helge; Strik, Werner; Wiest, Roland; Dierks, Thomas; Müller, Thomas J; Walther, Sebastian

    2013-02-01

    Little is known about the neurobiology of hypokinesia in schizophrenia. Therefore, the aim of this study was to investigate alterations of white matter motor pathways in schizophrenia and to relate our findings to objectively measured motor activity. We examined 21 schizophrenia patients and 21 healthy controls using diffusion tensor imaging and actigraphy. We applied a probabilistic fibre tracking approach to investigate pathways connecting the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the supplementary motor area proper (SMA-proper), the primary motor cortex (M1), the caudate nucleus, the striatum, the pallidum and the thalamus. Schizophrenia patients had lower activity levels than controls. In schizophrenia we found higher probability indices forming part of a bundle of interest (PIBI) in pathways connecting rACC, pre-SMA and SMA-proper as well as in pathways connecting M1 and pre-SMA with caudate nucleus, putamen, pallidum and thalamus and a reduced spatial extension of motor pathways in schizophrenia. There was a positive correlation between PIBI and activity level in the right pre-SMA-pallidum and the left M1-thalamus connection in healthy controls, and in the left pre-SMA-SMA-proper pathway in schizophrenia. Our results point to reduced volitional motor activity and altered motor pathway organisation in schizophrenia. The identified associations between the amount of movement and structural connectivity of motor pathways suggest dysfunction of cortico-basal ganglia pathways in the pathophysiology of hypokinesia in schizophrenia. Schizophrenia patients may use cortical pathways involving the supplementary motor area to compensate for basal ganglia dysfunction. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. A Biologically Inspired Computational Model of Basal Ganglia in Action Selection.

    PubMed

    Baston, Chiara; Ursino, Mauro

    2015-01-01

    The basal ganglia (BG) are a subcortical structure implicated in action selection. The aim of this work is to present a new cognitive neuroscience model of the BG, which aspires to represent a parsimonious balance between simplicity and completeness. The model includes the 3 main pathways operating in the BG circuitry, that is, the direct (Go), indirect (NoGo), and hyperdirect pathways. The main original aspects, compared with previous models, are the use of a two-term Hebb rule to train synapses in the striatum, based exclusively on neuronal activity changes caused by dopamine peaks or dips, and the role of the cholinergic interneurons (affected by dopamine themselves) during learning. Some examples are displayed, concerning a few paradigmatic cases: action selection in basal conditions, action selection in the presence of a strong conflict (where the role of the hyperdirect pathway emerges), synapse changes induced by phasic dopamine, and learning new actions based on a previous history of rewards and punishments. Finally, some simulations show model working in conditions of altered dopamine levels, to illustrate pathological cases (dopamine depletion in parkinsonian subjects or dopamine hypermedication). Due to its parsimonious approach, the model may represent a straightforward tool to analyze BG functionality in behavioral experiments.

  8. A Biologically Inspired Computational Model of Basal Ganglia in Action Selection

    PubMed Central

    Baston, Chiara

    2015-01-01

    The basal ganglia (BG) are a subcortical structure implicated in action selection. The aim of this work is to present a new cognitive neuroscience model of the BG, which aspires to represent a parsimonious balance between simplicity and completeness. The model includes the 3 main pathways operating in the BG circuitry, that is, the direct (Go), indirect (NoGo), and hyperdirect pathways. The main original aspects, compared with previous models, are the use of a two-term Hebb rule to train synapses in the striatum, based exclusively on neuronal activity changes caused by dopamine peaks or dips, and the role of the cholinergic interneurons (affected by dopamine themselves) during learning. Some examples are displayed, concerning a few paradigmatic cases: action selection in basal conditions, action selection in the presence of a strong conflict (where the role of the hyperdirect pathway emerges), synapse changes induced by phasic dopamine, and learning new actions based on a previous history of rewards and punishments. Finally, some simulations show model working in conditions of altered dopamine levels, to illustrate pathological cases (dopamine depletion in parkinsonian subjects or dopamine hypermedication). Due to its parsimonious approach, the model may represent a straightforward tool to analyze BG functionality in behavioral experiments. PMID:26640481

  9. Prevalence of anti-basal ganglia antibodies in adult obsessive-compulsive disorder: cross-sectional study.

    PubMed

    Nicholson, Timothy R J; Ferdinando, Sumudu; Krishnaiah, Ravikumar B; Anhoury, Sophie; Lennox, Belinda R; Mataix-Cols, David; Cleare, Anthony; Veale, David M; Drummond, Lynne M; Fineberg, Naomi A; Church, Andrew J; Giovannoni, Gavin; Heyman, Isobel

    2012-05-01

    Symptoms of obsessive-compulsive disorder (OCD) have been described in neuropsychiatric syndromes associated with streptococcal infections. It is proposed that antibodies raised against streptococcal proteins cross-react with neuronal proteins (antigens) in the brain, particularly in the basal ganglia, which is a brain region implicated in OCD pathogenesis. To test the hypothesis that post-streptococcal autoimmunity, directed against neuronal antigens, may contribute to the pathogenesis of OCD in adults. Ninety-six participants with OCD were tested for the presence of anti-streptolysin-O titres (ASOT) and the presence of anti-basal ganglia antibodies (ABGA) in a cross-sectional study. The ABGA were tested for with western blots using three recombinant antigens; aldolase C, enolase and pyruvate kinase. The findings were compared with those in a control group of individuals with depression (n = 33) and schizophrenia (n = 17). Positivity for ABGA was observed in 19/96 (19.8%) participants with OCD compared with 2/50 (4%) of controls (Fisher's exact test P = 0.012). The majority of positive OCD sera (13/19) had antibodies against the enolase antigen. No clinical variables were associated with ABGA positivity. Positivity for ASOT was not associated with ABGA positivity nor found at an increased incidence in participants with OCD compared with controls. These findings support the hypothesis that central nervous system autoimmunity may have an aetiological role in some adults with OCD. Further study is required to examine whether the antibodies concerned are pathogenic and whether exposure to streptococcal infection in vulnerable individuals is a risk factor for the development of OCD.

  10. Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution

    PubMed Central

    Schmidt, A; Denier, N; Magon, S; Radue, E-W; Huber, C G; Riecher-Rossler, A; Wiesbeck, G A; Lang, U E; Borgwardt, S; Walter, M

    2015-01-01

    Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy. PMID:25803496

  11. Consequences of partial and severe dopaminergic lesion on basal ganglia oscillatory activity and akinesia.

    PubMed

    Tseng, Kuei Y; Kargieman, Lucila; Gacio, Sebastian; Riquelme, Luis A; Murer, M Gustavo

    2005-11-01

    Severe chronic dopamine (DA) depletion increases the proportion of neurons in the basal ganglia that fire rhythmic bursts of action potential (LFO units) synchronously with the cortical oscillations. Here we report on how different levels of mesencephalic DA denervation affect substantia nigra pars reticulata (SNpr) neuronal activity in the rat and its relationship to akinesia (stepping test). Chronic nigrostriatal lesion induced with 0 (control group), 4, 6 or 8 microg of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle resulted in a dose-dependent decrease of tyrosine hydroxylase positive (TH+) neurons in the SN and ventral tegmental area (VTA). Although 4 microg of 6-OHDA reduced the number of TH+ neurons in the SN by approximately 60%, both stepping test performance and SNpr neuronal activity remained indistinguishable from control animals. By contrast, animals that received 6 microg of 6-OHDA showed a marked reduction of TH+ cells in the SN ( approximately 75%) and VTA ( approximately 55%), a significant stepping test deficit and an increased proportion of LFO units. These changes were not dramatically enhanced with 8 microg 6-OHDA, a dose that induced an extensive DA lesion (> 95%) in the SN and approximately 70% reduction of DA neurons in the VTA. These results suggest a threshold level of DA denervation for both the appearance of motor deficits and LFO units. Thus, the presence of LFO activity in the SNpr is not related to a complete nigrostriatal DA neuron depletion (ultimate stage parkinsonism); instead, it may reflect a functional disruption of cortico-basal ganglia dynamics associated with clinically relevant stages of the disease.

  12. Toward a functional analysis of the basal ganglia.

    PubMed

    Hayes, A E; Davidson, M C; Keele, S W; Rafal, R D

    1998-03-01

    Parkinson patients were tested in two paradigms to test the hypothesis that the basal ganglia are involved in the shifting of attentional set. Set shifting means a respecification of the conditions that regulate responding, a process sometimes referred to as an executive process. In one paradigm, upon the appearance of each stimulus, subjects were instructed to respond either to its color or to its shape. In a second paradigm, subjects learned to produce short sequences of three keypresses in response to two arbitrary stimuli. Reaction times were compared for the cases where set either remained the same or changed for two successive stimuli. Parkinson patients were slow to change set compared to controls. Parkinson patients were also less able to filter the competing but irrelevant set than were control subjects. The switching deficit appears to be dopamine based; the magnitude of the shifting deficit was related to the degree to which 1-dopa-based medication ameliorated patients' motor symptoms. Moreover, temporary withholding of medication, a so-called off manipulation, increased the time to switch. Using the framework of equilibrium point theory of movement, we discuss how a set switching deficit may also underlie clinical motor disturbances seen in Parkinson's disease.

  13. A Biologically Plausible Action Selection System for Cognitive Architectures: Implications of Basal Ganglia Anatomy for Learning and Decision-Making Models

    ERIC Educational Resources Information Center

    Stocco, Andrea

    2018-01-01

    Several attempts have been made previously to provide a biological grounding for cognitive architectures by relating their components to the computations of specific brain circuits. Often, the architecture's action selection system is identified with the basal ganglia. However, this identification overlooks one of the most important features of…

  14. Pharmacologic MRI (phMRI) as a tool to differentiate Parkinson's disease-related from age-related changes in basal ganglia function.

    PubMed

    Andersen, Anders H; Hardy, Peter A; Forman, Eric; Gerhardt, Greg A; Gash, Don M; Grondin, Richard C; Zhang, Zhiming

    2015-02-01

    The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. Although the pathophysiology of PD has been studied extensively, less is known about the functional changes taking place in the basal ganglia circuitry with age. To specifically address this issue, 3 groups of rhesus macaques were studied: normal middle-aged animals (used as controls), middle-aged animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, and aged animals (>20 years old) with declines in motor function. All animals underwent the same behavioral and pharmacologic magnetic resonance imaging (phMRI) procedures to measure changes in basal ganglia function in response to dopaminergic drug challenges consisting of apomorphine administration followed by either a D1 (SCH23390) or a D2 (raclopride) receptor antagonist. Significant functional changes were predominantly seen in the external segment of the globus pallidus (GPe) in aged animals and in the striatum (caudate nucleus and putamen) in MPTP-lesioned animals. Despite significant differences seen in the putamen and GPe between MPTP-lesioned versus aged animals, a similar response profile to dopaminergic stimulations was found between these 2 groups in the internal segment of the GP. In contrast, the pharmacologic responses seen in the control animals were much milder compared with the other 2 groups in all the examined areas. Our phMRI findings in MPTP-lesioned parkinsonian and aged animals suggest that changes in basal ganglia function in the elderly may differ from those seen in parkinsonian patients and that phMRI could be used to distinguish PD from other age-associated functional alterations in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Treatment of biotin-responsive basal ganglia disease: Open comparative study between the combination of biotin plus thiamine versus thiamine alone.

    PubMed

    Tabarki, Brahim; Alfadhel, Majid; AlShahwan, Saad; Hundallah, Khaled; AlShafi, Shatha; AlHashem, Amel

    2015-09-01

    To compare the combination of biotin plus thiamine to thiamine alone in treating patients with biotin-responsive basal ganglia disease in an open-label prospective, comparative study. twenty patients with genetically proven biotin-responsive basal ganglia disease were enrolled, and received for at least 30 months a combination of biotin plus thiamine or thiamine alone. The outcome measures included duration of the crisis, number of recurrence/admissions, the last neurological examination, the severity of dystonia using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), and the brain MRI findings during the crisis and after 30 months of follow-up. Ten children with a mean age of 6 years(1/2) were recruited in the biotin plus thiamine group (group 1) and ten children (6 females and 4 males) with a mean age of 6 years and 2 months were recruited in the thiamine group (group 2). After 2 years of follow-up treatment, 6 of 20 children achieved complete remission, 10 had minimal sequelae in the form of mild dystonia and dysarthria (improvement of the BFMDRS, mean: 80%), and 4 had severe neurologic sequelae. All these 4 patients had delayed diagnosis and management. Regarding outcome measures, both groups have a similar outcome regarding the number of recurrences, the neurologic sequelae (mean BFMDS score between the groups, p = 0.84), and the brain MRI findings. The only difference was the duration of the acute crisis: group 1 had faster recovery (2 days), versus 3 days in group 2 (p = 0.005). Our study suggests that over 30 months of treatment, the combination of biotin plus thiamine is not superior to thiamine alone in the treatment of biotin-responsive basal ganglia disease. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  16. Tremor amplitude and tremor frequency variability in Parkinson's disease is dependent on activity and synchronisation of central oscillators in basal ganglia.

    PubMed

    Bartolić, Andrej; Pirtosek, Zvezdan; Rozman, Janez; Ribaric, Samo

    2010-02-01

    Rest tremor is one of the four main clinical features of Parkinson's disease (PD), besides rigidity, bradykinesia and postural instability. While rigidity, bradykinesia and postural instability can be explained with changes in neurotransmitter concentrations and neuronal activity in basal ganglia, the pathogenesis of parkinsonian tremor is not fully understood. According to the leading hypothesis tremor is generated by neurons or groups of neurons in the basal ganglia which act as central oscillators and generate repetitive impulses to the muscles of the body parts involved. The exact morphological substrate for central oscillators and the mechanisms leading to their activation are still an object of debate. Peripheral neural structures exert modulatory influence on tremor amplitude, but not on tremor frequency. We hypothesise that rest tremor in PD is the result of two mechanisms: increased activity and increased synchronisation of central oscillators. We tested our hypothesis by demonstrating that the reduction in rest tremor amplitude is accompanied by increased variability of tremor frequency. The reduction of tremor amplitude is attributed to decreased activity and poor synchronisation of central oscillators in basal ganglia; the increased variability of tremor frequency is attributed to poor synchronisation of the central oscillators. In addition, we demonstrated that the recurrence of clinically visible rest tremor is accompanied by a reduction in tremor frequency variability. This reduction is attributed to increased synchronisation of central oscillators in basal ganglia. We argue that both mechanisms, increased activity of central oscillators and increased synchronisation of central oscillators, are equally important and we predict that tremor becomes clinically evident only when both mechanisms are active at the same time. In circumstances when one of the mechanisms is suppressed tremor amplitude becomes markedly reduced. On the one hand, if the number

  17. Robust Representation of Stable Object Values in the Oculomotor Basal Ganglia

    PubMed Central

    Yasuda, Masaharu; Yamamoto, Shinya; Hikosaka, Okihide

    2012-01-01

    Our gaze tends to be directed to objects previously associated with rewards. Such object values change flexibly or remain stable. Here we present evidence that the monkey substantia nigra pars reticulata (SNr) in the basal ganglia represents stable, rather than flexible, object values. After across-day learning of object–reward association, SNr neurons gradually showed a response bias to surprisingly many visual objects: inhibition to high-valued objects and excitation to low-valued objects. Many of these neurons were shown to project to the ipsilateral superior colliculus. This neuronal bias remained intact even after >100 d without further learning. In parallel with the neuronal bias, the monkeys tended to look at high-valued objects. The neuronal and behavioral biases were present even if no value was associated during testing. These results suggest that SNr neurons bias the gaze toward objects that were consistently associated with high values in one’s history. PMID:23175843

  18. Electrophysiology of Basal Ganglia and Cortex in Models of Parkinson Disease

    PubMed Central

    Ellens, Damien J.; Leventhal, Daniel K.

    2014-01-01

    Incomplete understanding of the systems-level pathophysiology of Parkinson Disease (PD) remains a significant barrier to improving its treatment. Substantial progress has been made, however, due to the availability of neurotoxins that selectively target monoaminergic (in particular, dopaminergic) neurons. This review discusses the in vivo electrophysiology of basal ganglia (BG), thalamic, and cortical regions after dopamine-depleting lesions. These include firing rate changes, neuronal burst-firing, neuronal oscillations, and neuronal synchrony that result from a combination of local microanatomic changes and network-level interactions. While much is known of the clinical and electrophysiological phenomenology of dopamine loss, a critical gap in our conception of PD pathophysiology is the link between them. We discuss potential mechanisms by which these systems-level electrophysiological changes may emerge, as well as how they may relate to clinical parkinsonism. Proposals for an updated understanding of BG function are reviewed, with an emphasis on how emerging frameworks will guide future research into the pathophysiology and treatment of PD. PMID:23948994

  19. Basal ganglia circuit loops, dopamine and motivation: A review and enquiry

    PubMed Central

    Ikemoto, Satoshi; Yang, Chen; Tan, Aaron

    2015-01-01

    Dopamine neurons located in the midbrain play a role in motivation that regulates approach behavior (approach motivation). In addition, activation and inactivation of dopamine neurons regulate mood and induce reward and aversion, respectively. Accumulating evidence suggests that such motivational role of dopamine neurons is not limited to those located in the ventral tegmental area, but also in the substantia nigra. The present paper reviews previous rodent work concerning dopamine’s role in approach motivation and the connectivity of dopamine neurons, and proposes two working models: One concerns the relationship between extracellular dopamine concentration and approach motivation. High, moderate and low concentrations of extracellular dopamine induce euphoric, seeking and aversive states, respectively. The other concerns circuit loops involving the cerebral cortex, basal ganglia, thalamus, epithalamus, and midbrain through which dopaminergic activity alters approach motivation. These models should help to generate hypothesis-driven research and provide insights for understanding altered states associated with drugs of abuse and affective disorders. PMID:25907747

  20. Effects of Electrical and Optogenetic Deep Brain Stimulation on Synchronized Oscillatory Activity in Parkinsonian Basal Ganglia.

    PubMed

    Ratnadurai-Giridharan, Shivakeshavan; Cheung, Chung C; Rubchinsky, Leonid L

    2017-11-01

    Conventional deep brain stimulation of basal ganglia uses high-frequency regular electrical pulses to treat Parkinsonian motor symptoms but has a series of limitations. Relatively new and not yet clinically tested, optogenetic stimulation is an effective experimental stimulation technique to affect pathological network dynamics. We compared the effects of electrical and optogenetic stimulation of the basal gangliaon the pathologicalParkinsonian rhythmic neural activity. We studied the network response to electrical stimulation and excitatory and inhibitory optogenetic stimulations. Different stimulations exhibit different interactions with pathological activity in the network. We studied these interactions for different network and stimulation parameter values. Optogenetic stimulation was found to be more efficient than electrical stimulation in suppressing pathological rhythmicity. Our findings indicate that optogenetic control of neural synchrony may be more efficacious than electrical control because of the different ways of how stimulations interact with network dynamics.

  1. Blood-nerve barrier: distribution of anionic sites on the endothelial plasma membrane and basal lamina of dorsal root ganglia.

    PubMed

    Bush, M S; Reid, A R; Allt, G

    1991-09-01

    Previous investigations of the blood-nerve barrier have correlated the greater permeability of ganglionic endoneurial vessels, compared to those of nerve trunks, with the presence of fenestrations and open intercellular junctions. Recent studies have demonstrated reduced endothelial cell surface charge in blood vessels showing greater permeability. To determine the distribution of anionic sites on the plasma membranes and basal laminae of endothelial cells in dorsal root ganglia, cationic colloidal gold and cationic ferritin were used. Electron microscopy revealed the existence of endothelial microdomains with differing labelling densities. Labelling indicated that caveolar and fenestral diaphragms and basal laminae are highly anionic at physiological pH, luminal plasma membranes and endothelial processes are moderately charged and abluminal plasma membranes are weakly anionic. Tracers did not occur in caveolae or cytoplasmic vesicles. In vitro tracer experiments at pH values of 7.3, 5.0, 3.5 and 2.0 indicated that the anionic charge on the various endothelial domains was contributed by chemical groups with differing pKa values. In summary, the labelling of ganglionic and sciatic nerve vessels was similar except for the heavy labelling of diaphragms in a minority of endoneurial vessels in ganglia. This difference is likely to account in part for the greater permeability of ganglionic endoneurial vessels. The results are discussed with regard to the blood-nerve and -brain barriers and vascular permeability in other tissues and a comparison made between the ultrastructure and anionic microdomains of epi-, peri- and endoneurial vessels of dorsal root ganglia and sciatic nerves.

  2. Cognitive and motor functioning in a patient with selective infarction of the left basal ganglia: evidence for decreased non-routine response selection and performance.

    PubMed

    Troyer, Angela K; Black, Sandra E; Armilio, Maria L; Moscovitch, Morris

    2004-01-01

    Focal damage to the basal ganglia is relatively rare, and little is known about the cognitive effects of damage to specific basal ganglia structures. A 28-year-old, highly educated male (patient RI) sustained a unilateral left ischemic infarction involving primarily the putamen and secondarily the head of the caudate and the anterior internal capsule. Two detailed neuropsychological assessments, at 3 and 16 months post-infarction, revealed that a majority of cognitive abilities were spared. RI's general intelligence, simple attention, concept formation, cognitive flexibility, and explicit memory were unaffected. Select cognitive abilities were affected, and these appeared to be related to direct involvement of the putamen and/or to indirect disruption of circuits between the basal ganglia and frontal lobes. Consistent with involvement of the left putamen, RI showed micrographia with his right hand. Interestingly, his micrographia was context-dependent, appearing only when verbal expression was involved (e.g., present when writing spontaneously, but not when copying sentences or when drawing). Evidence of disruption to frontal systems included variably decreased sustained attention, mildly decreased ability to generate words and to generate ideas, and significantly impaired abstraction ability in both verbal and visual modalities. Although there are several possible interpretations for these findings, this pattern of cognitive and motor functioning is consistent with neuroimaging research suggesting that the frontal/subcortical circuit between the putamen and frontal motor areas plays a role in non-routine response selection and performance.

  3. Role of Basal Ganglia in Sleep–Wake Regulation: Neural Circuitry and Clinical Significance

    PubMed Central

    Vetrivelan, Ramalingam; Qiu, Mei-Hong; Chang, Celene; Lu, Jun

    2010-01-01

    Researchers over the last decade have made substantial progress toward understanding the roles of dopamine and the basal ganglia (BG) in the control of sleep–wake behavior. In this review, we outline recent advancements regarding dopaminergic modulation of sleep through the BG and extra-BG sites. Our main hypothesis is that dopamine promotes sleep by its action on the D2 receptors in the BG and promotes wakefulness by its action on D1 and D2 receptors in the extra-BG sites. This hypothesis implicates dopamine depletion in the BG (such as in Parkinson's disease) in causing frequent nighttime arousal and overall insomnia. Furthermore, the arousal effects of psychostimulants (methamphetamine, cocaine, and modafinil) may be linked to the ventral periaquductal gray (vPAG) dopaminergic circuitry targeting the extra-BG sleep–wake network. PMID:21151379

  4. Presynaptic Inhibition in the Striatum of the Basal Ganglia Improves Pattern Classification and Thus Promotes Superior Goal Selection

    PubMed Central

    Schwab, David J.; Houk, James C.

    2015-01-01

    This review article takes a multidisciplinary approach to understand how presynaptic inhibition in the striatum of the basal ganglia (BG) contributes to pattern classification and the selection of goals that control behavior. It is a difficult problem both because it is multidimensional and because it is has complex system dynamics. We focus on the striatum because, as the main site for input to the BG, it gets to decide what goals are important to consider. PMID:26696840

  5. A Common Function of Basal Ganglia-Cortical Circuits Subserving Speed in Both Motor and Cognitive Domains.

    PubMed

    Hanakawa, Takashi; Goldfine, Andrew M; Hallett, Mark

    2017-01-01

    Distinct regions of the frontal cortex connect with their basal ganglia and thalamic counterparts, constituting largely segregated basal ganglia-thalamo-cortical (BTC) circuits. However, any common role of the BTC circuits in different behavioral domains remains unclear. Indeed, whether dysfunctional motor and cognitive BTC circuits are responsible for motor slowing and cognitive slowing, respectively, in Parkinson's disease (PD) is a matter of debate. Here, we used an effortful behavioral paradigm in which the effects of task rate on accuracy were tested in movement, imagery, and calculation tasks in humans. Using nonlinear fitting, we separated baseline accuracy ( A base ) and "agility" (ability to function quickly) components of performance in healthy participants and then confirmed reduced agility and preserved A base for the three tasks in PD. Using functional magnetic resonance imaging (fMRI) and diffusion tractography, we explored the neural substrates underlying speeded performance of the three tasks in healthy participants, suggesting the involvement of distinct BTC circuits in cognitive and motor agility. Language and motor BTC circuits were specifically active during speeded performance of the calculation and movement tasks, respectively, whereas premotor BTC circuits revealed activity for speeded performance of all tasks. Finally, PD showed reduced task rate-correlated activity in the language BTC circuits for speeded calculation, in the premotor BTC circuit for speeded imagery, and in the motor BTC circuits for speeded movement, as compared with controls. The present study casts light on the anatomo-functional organization of the BTC circuits and their parallel roles in invigorating movement and cognition through a function of dopamine.

  6. A Common Function of Basal Ganglia-Cortical Circuits Subserving Speed in Both Motor and Cognitive Domains

    PubMed Central

    2017-01-01

    Abstract Distinct regions of the frontal cortex connect with their basal ganglia and thalamic counterparts, constituting largely segregated basal ganglia-thalamo-cortical (BTC) circuits. However, any common role of the BTC circuits in different behavioral domains remains unclear. Indeed, whether dysfunctional motor and cognitive BTC circuits are responsible for motor slowing and cognitive slowing, respectively, in Parkinson’s disease (PD) is a matter of debate. Here, we used an effortful behavioral paradigm in which the effects of task rate on accuracy were tested in movement, imagery, and calculation tasks in humans. Using nonlinear fitting, we separated baseline accuracy (Abase) and “agility” (ability to function quickly) components of performance in healthy participants and then confirmed reduced agility and preserved Abase for the three tasks in PD. Using functional magnetic resonance imaging (fMRI) and diffusion tractography, we explored the neural substrates underlying speeded performance of the three tasks in healthy participants, suggesting the involvement of distinct BTC circuits in cognitive and motor agility. Language and motor BTC circuits were specifically active during speeded performance of the calculation and movement tasks, respectively, whereas premotor BTC circuits revealed activity for speeded performance of all tasks. Finally, PD showed reduced task rate-correlated activity in the language BTC circuits for speeded calculation, in the premotor BTC circuit for speeded imagery, and in the motor BTC circuits for speeded movement, as compared with controls. The present study casts light on the anatomo-functional organization of the BTC circuits and their parallel roles in invigorating movement and cognition through a function of dopamine. PMID:29379873

  7. Functional Connectivity of Insula, Basal Ganglia, and Prefrontal Executive Control Networks during Hypoglycemia in Type 1 Diabetes

    PubMed Central

    Simonson, Donald C.; Nickerson, Lisa D.; Flores, Veronica L.; Siracusa, Tamar; Hager, Brandon; Lyoo, In Kyoon; Renshaw, Perry F.; Jacobson, Alan M.

    2015-01-01

    Human brain networks mediating interoceptive, behavioral, and cognitive aspects of glycemic control are not well studied. Using group independent component analysis with dual-regression approach of functional magnetic resonance imaging data, we examined the functional connectivity changes of large-scale resting state networks during sequential euglycemic–hypoglycemic clamp studies in patients with type 1 diabetes and nondiabetic controls and how these changes during hypoglycemia were related to symptoms of hypoglycemia awareness and to concurrent glycosylated hemoglobin (HbA1c) levels. During hypoglycemia, diabetic patients showed increased functional connectivity of the right anterior insula and the prefrontal cortex within the executive control network, which was associated with higher HbA1c. Controls showed decreased functional connectivity of the right anterior insula with the cerebellum/basal ganglia network and of temporal regions within the temporal pole network and increased functional connectivity in the default mode and sensorimotor networks. Functional connectivity reductions in the right basal ganglia were correlated with increases of self-reported hypoglycemic symptoms in controls but not in patients. Resting state networks that showed different group functional connectivity during hypoglycemia may be most sensitive to glycemic environment, and their connectivity patterns may have adapted to repeated glycemic excursions present in type 1 diabetes. Our results suggest that basal ganglia and insula mediation of interoceptive awareness during hypoglycemia is altered in type 1 diabetes. These changes could be neuroplastic adaptations to frequent hypoglycemic experiences. Functional connectivity changes in the insula and prefrontal cognitive networks could also reflect an adaptation to changes in brain metabolic pathways associated with chronic hyperglycemia. SIGNIFICANCE STATEMENT The major factor limiting improved glucose control in type 1 diabetes is

  8. Individual differences in brainstem and basal ganglia structure predict postural control and balance loss in young and older adults.

    PubMed

    Boisgontier, Matthieu P; Cheval, Boris; Chalavi, Sima; van Ruitenbeek, Peter; Leunissen, Inge; Levin, Oron; Nieuwboer, Alice; Swinnen, Stephan P

    2017-02-01

    It remains unclear which specific brain regions are the most critical for human postural control and balance, and whether they mediate the effect of age. Here, associations between postural performance and corticosubcortical brain regions were examined in young and older adults using multiple structural imaging and linear mixed models. Results showed that of the regions involved in posture, the brainstem was the strongest predictor of postural control and balance: lower brainstem volume predicted larger center of pressure deviation and higher odds of balance loss. Analyses of white and gray matter in the brainstem showed that the pedunculopontine nucleus area appeared to be critical for postural control in both young and older adults. In addition, the brainstem mediated the effect of age on postural control, underscoring the brainstem's fundamental role in aging. Conversely, lower basal ganglia volume predicted better postural performance, suggesting an association between greater neural resources in the basal ganglia and greater movement vigor, resulting in exaggerated postural adjustments. Finally, results showed that practice, shorter height and heavier weight (i.e., higher body mass index), higher total physical activity, and larger ankle active (but not passive) range of motion were predictive of more stable posture, irrespective of age. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Associations of olfactory bulb and depth of olfactory sulcus with basal ganglia and hippocampus in patients with Parkinson's disease.

    PubMed

    Tanik, Nermin; Serin, Halil Ibrahim; Celikbilek, Asuman; Inan, Levent Ertugrul; Gundogdu, Fatma

    2016-05-04

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by hyposmia in the preclinical stages. We investigated the relationships of olfactory bulb (OB) volume and olfactory sulcus (OS) depth with basal ganglia and hippocampal volumes. The study included 25 patients with PD and 40 age- and sex-matched control subjects. Idiopathic PD was diagnosed according to published diagnostic criteria. The Hoehn and Yahr (HY) scale, the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS III), and the Mini-Mental State Examination (MMSE) were administered to participants. Volumetric measurements of olfactory structures, the basal ganglia, and hippocampus were performed using magnetic resonance imaging (MRI). OB volume and OS depth were significantly reduced in PD patients compared to healthy control subjects (p<0.001 and p<0.001, respectively). The OB and left putamen volumes were significantly correlated (p=0.048), and the depth of the right OS was significantly correlated with right hippocampal volume (p=0.018). We found significant correlations between OB and putamen volumes and OS depth and hippocampal volume. Our study is the first to demonstrate associations of olfactory structures with the putamen and hippocampus using MRI volumetric measurements. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. The effects of age on resting state functional connectivity of the basal ganglia from young to middle adulthood.

    PubMed

    Manza, Peter; Zhang, Sheng; Hu, Sien; Chao, Herta H; Leung, Hoi-Chung; Li, Chiang-Shan R

    2015-02-15

    The basal ganglia nuclei are critical for a variety of cognitive and motor functions. Much work has shown age-related structural changes of the basal ganglia. Yet less is known about how the functional interactions of these regions with the cerebral cortex and the cerebellum change throughout the lifespan. Here, we took advantage of a convenient sample and examined resting state functional magnetic resonance imaging data from 250 adults 18 to 49 years of age, focusing specifically on the caudate nucleus, pallidum, putamen, and ventral tegmental area/substantia nigra (VTA/SN). There are a few main findings to report. First, with age, caudate head connectivity increased with a large region of ventromedial prefrontal/medial orbitofrontal cortex. Second, across all subjects, pallidum and putamen showed negative connectivity with default mode network (DMN) regions such as the ventromedial prefrontal cortex and posterior cingulate cortex, in support of anti-correlation of the "task-positive" network (TPN) and DMN. This negative connectivity was reduced with age. Furthermore, pallidum, posterior putamen and VTA/SN connectivity to other TPN regions, such as somatomotor cortex, decreased with age. These results highlight a distinct effect of age on cerebral functional connectivity of the dorsal striatum and VTA/SN from young to middle adulthood and may help research investigating the etiologies or monitoring outcomes of neuropsychiatric conditions that implicate dopaminergic dysfunction. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Default mode network, motor network, dorsal and ventral basal ganglia networks in the rat brain: comparison to human networks using resting state-fMRI.

    PubMed

    Sierakowiak, Adam; Monnot, Cyril; Aski, Sahar Nikkhou; Uppman, Martin; Li, Tie-Qiang; Damberg, Peter; Brené, Stefan

    2015-01-01

    Rodent models are developed to enhance understanding of the underlying biology of different brain disorders. However, before interpreting findings from animal models in a translational aspect to understand human disease, a fundamental step is to first have knowledge of similarities and differences of the biological systems studied. In this study, we analyzed and verified four known networks termed: default mode network, motor network, dorsal basal ganglia network, and ventral basal ganglia network using resting state functional MRI (rsfMRI) in humans and rats. Our work supports the notion that humans and rats have common robust resting state brain networks and that rsfMRI can be used as a translational tool when validating animal models of brain disorders. In the future, rsfMRI may be used, in addition to short-term interventions, to characterize longitudinal effects on functional brain networks after long-term intervention in humans and rats.

  12. Default Mode Network, Motor Network, Dorsal and Ventral Basal Ganglia Networks in the Rat Brain: Comparison to Human Networks Using Resting State-fMRI

    PubMed Central

    Sierakowiak, Adam; Monnot, Cyril; Aski, Sahar Nikkhou; Uppman, Martin; Li, Tie-Qiang; Damberg, Peter; Brené, Stefan

    2015-01-01

    Rodent models are developed to enhance understanding of the underlying biology of different brain disorders. However, before interpreting findings from animal models in a translational aspect to understand human disease, a fundamental step is to first have knowledge of similarities and differences of the biological systems studied. In this study, we analyzed and verified four known networks termed: default mode network, motor network, dorsal basal ganglia network, and ventral basal ganglia network using resting state functional MRI (rsfMRI) in humans and rats. Our work supports the notion that humans and rats have common robust resting state brain networks and that rsfMRI can be used as a translational tool when validating animal models of brain disorders. In the future, rsfMRI may be used, in addition to short-term interventions, to characterize longitudinal effects on functional brain networks after long-term intervention in humans and rats. PMID:25789862

  13. Individual differences in the Simon effect are underpinned by differences in the competitive dynamics in the basal ganglia: An experimental verification and a computational model.

    PubMed

    Stocco, Andrea; Murray, Nicole L; Yamasaki, Brianna L; Renno, Taylor J; Nguyen, Jimmy; Prat, Chantel S

    2017-07-01

    Cognitive control is thought to be made possible by the activity of the prefrontal cortex, which selectively uses task-specific representations to bias the selection of task-appropriate responses over more automated, but inappropriate, ones. Recent models have suggested, however, that prefrontal representations are in turn controlled by the basal ganglia. In particular, neurophysiological considerations suggest that the basal ganglia's indirect pathway plays a pivotal role in preventing irrelevant information from being incorporated into a task, thus reducing response interference due to the processing of inappropriate stimuli dimensions. Here, we test this hypothesis by showing that individual differences in a non-verbal cognitive control task (the Simon task) are correlated with performance on a decision-making task (the Probabilistic Stimulus Selection task) that tracks the contribution of the indirect pathway. Specifically, the higher the effect of the indirect pathway, the smaller was the behavioral costs associated with suppressing interference in incongruent trials. Additionally, it was found that this correlation was driven by individual differences in incongruent trials only (with little effect on congruent ones) and specific to the indirect pathway (with almost no correlation with the effect of the direct pathways). Finally, it is shown that this pattern of results is precisely what is predicted when competitive dynamics of the basal ganglia are added to the selective attention component of a simple model of the Simon task, thus showing that our experimental results can be fully explained by our initial hypothesis. Published by Elsevier B.V.

  14. Singing-related neural activity distinguishes two putative pallidal cell types in the songbird basal ganglia: comparison to the primate internal and external pallidal segments

    PubMed Central

    Goldberg, Jesse H.; Adler, Avital; Bergman, Hagai; Fee, Michale S.

    2010-01-01

    The songbird area X is a basal ganglia homologue that contains two pallidal cell types—local neurons that project within the basal ganglia and output neurons that project to the thalamus. Based on these projections, it has been proposed that these classes are structurally homologous to the primate external (GPe) and internal (GPi) pallidal segments. To test the hypothesis that the two area X pallidal types are functionally homologous to GPe and GPi neurons, we recorded from neurons in area X of singing juvenile male zebra finches, and directly compare their firing patterns to neurons recorded in the primate pallidus. In area X, we find two cell classes that exhibited high firing (HF) rates (>60Hz) characteristic of pallidal neurons. HF-1 neurons, like most GPe neurons we examined, exhibited large firing rate modulations, including bursts and long pauses. In contrast, HF-2 neurons, like GPi neurons, discharged continuously without bursts or long pauses. To test if HF-2 neurons were the output neurons that project to the thalamus, we next recorded directly from pallidal axon terminals in thalamic nucleus DLM, and found that all terminals exhibited singing-related firing patterns indistinguishable from HF-2 neurons. Our data show that singing-related neural activity distinguishes two putative pallidal cell types in area X: thalamus-projecting neurons that exhibit activity similar to the primate GPi, and non-thalamus-projecting neurons that exhibit activity similar to the primate GPe. These results suggest that song learning in birds and motor learning in mammals employ conserved basal ganglia signaling strategies. PMID:20484651

  15. A cortical motor nucleus drives the basal ganglia-recipient thalamus in singing birds

    PubMed Central

    Goldberg, Jesse H.

    2012-01-01

    The pallido-recipient thalamus transmits information from the basal ganglia (BG) to the cortex and plays a critical role motor initiation and learning. Thalamic activity is strongly inhibited by pallidal inputs from the BG, but the role of non-pallidal inputs, such as excitatory inputs from cortex, is unclear. We have recorded simultaneously from presynaptic pallidal axon terminals and postsynaptic thalamocortical neurons in a BG-recipient thalamic nucleus necessary for vocal variability and learning in zebra finches. We found that song-locked rate modulations in the thalamus could not be explained by pallidal inputs alone, and persisted following pallidal lesion. Instead, thalamic activity was likely driven by inputs from a motor ‘cortical’ nucleus also necessary for singing. These findings suggest a role for cortical inputs to the pallido-recipient thalamus in driving premotor signals important for exploratory behavior and learning. PMID:22327474

  16. Technical integration of hippocampus, Basal Ganglia and physical models for spatial navigation.

    PubMed

    Fox, Charles; Humphries, Mark; Mitchinson, Ben; Kiss, Tamas; Somogyvari, Zoltan; Prescott, Tony

    2009-01-01

    Computational neuroscience is increasingly moving beyond modeling individual neurons or neural systems to consider the integration of multiple models, often constructed by different research groups. We report on our preliminary technical integration of recent hippocampal formation, basal ganglia and physical environment models, together with visualisation tools, as a case study in the use of Python across the modelling tool-chain. We do not present new modeling results here. The architecture incorporates leaky-integrator and rate-coded neurons, a 3D environment with collision detection and tactile sensors, 3D graphics and 2D plots. We found Python to be a flexible platform, offering a significant reduction in development time, without a corresponding significant increase in execution time. We illustrate this by implementing a part of the model in various alternative languages and coding styles, and comparing their execution times. For very large-scale system integration, communication with other languages and parallel execution may be required, which we demonstrate using the BRAHMS framework's Python bindings.

  17. A computational model of Dopamine and Acetylcholine aberrant learning in Basal Ganglia.

    PubMed

    Baston, Chiara; Ursino, Mauro

    2015-01-01

    Basal Ganglia (BG) are implied in many motor and cognitive tasks, such as action selection, and have a central role in many pathologies, primarily Parkinson Disease. In the present work, we use a recently developed biologically inspired BG model to analyze how the dopamine (DA) level can affect the temporal response during action selection, and the capacity to learn new actions following rewards and punishments. The model incorporates the 3 main pathways (direct, indirect and hyperdirect) working in BG functioning. The behavior of 2 alternative networks (the first with normal DA levels, the second with reduced DA) is analyzed both in untrained conditions, and during training performed in different epochs. The results show that reduced DA causes delayed temporal responses in the untrained network, and difficult of learning during training, characterized by the necessity of much more epochs. The results provide interesting hints to understand the behavior of healthy and dopamine depleted subjects, such as parkinsonian patients.

  18. Visuo-motor and cognitive procedural learning in children with basal ganglia pathology.

    PubMed

    Mayor-Dubois, C; Maeder, P; Zesiger, P; Roulet-Perez, E

    2010-06-01

    We investigated procedural learning in 18 children with basal ganglia (BG) lesions or dysfunctions of various aetiologies, using a visuo-motor learning test, the Serial Reaction Time (SRT) task, and a cognitive learning test, the Probabilistic Classification Learning (PCL) task. We compared patients with early (<1 year old, n=9), later onset (>6 years old, n=7) or progressive disorder (idiopathic dystonia, n=2). All patients showed deficits in both visuo-motor and cognitive domains, except those with idiopathic dystonia, who displayed preserved classification learning skills. Impairments seem to be independent from the age of onset of pathology. As far as we know, this study is the first to investigate motor and cognitive procedural learning in children with BG damage. Procedural impairments were documented whatever the aetiology of the BG damage/dysfunction and time of pathology onset, thus supporting the claim of very early skill learning development and lack of plasticity in case of damage. Copyright 2010 Elsevier Ltd. All rights reserved.

  19. IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice

    PubMed Central

    Hisatsune, Chihiro; Miyamoto, Hiroyuki; Hirono, Moritoshi; Yamaguchi, Naohide; Sugawara, Takeyuki; Ogawa, Naoko; Ebisui, Etsuko; Ohshima, Toshio; Yamada, Masahisa; Hensch, Takao K.; Hattori, Mitsuharu; Mikoshiba, Katsuhiko

    2013-01-01

    The type 1 inositol 1,4,5- trisphosphate receptor (IP3R1) is a Ca2+ channel on the endoplasmic reticulum and is a predominant isoform in the brain among the three types of IP3Rs. Mice lacking IP3R1 show seizure-like behavior; however the cellular and neural circuit mechanism by which IP3R1 deletion causes the abnormal movements is unknown. Here, we found that the conditional knockout mice lacking IP3R1 specifically in the cerebellum and brainstem experience dystonia and show that cerebellar Purkinje cell (PC) firing patterns were coupled to specific dystonic movements. Recordings in freely behaving mice revealed epochs of low and high frequency PC complex spikes linked to body extension and rigidity, respectively. Remarkably, dystonic symptoms were independent of the basal ganglia, and could be rescued by inactivation of the cerebellum, inferior olive or in the absence of PCs. These findings implicate IP3R1-dependent PC firing patterns in cerebellum in motor coordination and the expression of dystonia through the olivo-cerebellar pathway. PMID:24109434

  20. Basal ganglia atrophy in prodromal Huntington’s disease is detectable over one year using automated segmentation

    PubMed Central

    Majid, DS Adnan; Aron, Adam R; Thompson, Wesley; Sheldon, Sarah; Hamza, Samar; Stoffers, Diederick; Holland, Dominic; Goldstein, Jody; Corey-Bloom, Jody; Dale, Anders M

    2017-01-01

    Background Future clinical trials of neuroprotection in prodromal Huntington’s (known as preHD) require sensitive in vivo imaging biomarkers to track disease progression over the shortest period. Since basal ganglia atrophy is the most prominent structural characteristic of Huntington’s pathology, systematic assessment of longitudinal subcortical atrophy holds great potential for future biomarker development. Methods We studied 36 preHD and 22 age-matched controls using a novel method to quantify regional change from T1-weighted structural images acquired one year apart. We assessed cross-sectional volume differences and longitudinal volumetric change in seven subcortical structures – the accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Results At baseline, accumbens, caudate, pallidum, and putamen volumes were reduced in preHD vs. controls (all p<.01). Longitudinally, atrophy was greater in preHD than controls in the caudate, pallidum, and putamen (all p<.01). Each structure showed a large between-group effect size, especially the pallidum where Cohen’s d was 1.21. Using pallidal atrophy as a biomarker, we estimate that a hypothetical one-year neuroprotection study would require only 35 preHD per arm to detect a 50% slowing in atrophy and only 138 preHD per arm to detect a 25% slowing in atrophy. Conclusions The effect sizes calculated for preHD basal ganglia atrophy over one year are some of the largest reported to date. Consequently, this translates to strikingly small sample size estimates that will greatly facilitate any future neuroprotection study. This underscores the utility of this automatic image segmentation and longitudinal nonlinear registration method for upcoming studies of preHD and other neurodegenerative disorders. PMID:21932302

  1. Gait variability and basal ganglia disorders: stride-to-stride variations of gait cycle timing in Parkinson's disease and Huntington's disease

    NASA Technical Reports Server (NTRS)

    Hausdorff, J. M.; Cudkowicz, M. E.; Firtion, R.; Wei, J. Y.; Goldberger, A. L.

    1998-01-01

    The basal ganglia are thought to play an important role in regulating motor programs involved in gait and in the fluidity and sequencing of movement. We postulated that the ability to maintain a steady gait, with low stride-to-stride variability of gait cycle timing and its subphases, would be diminished with both Parkinson's disease (PD) and Huntington's disease (HD). To test this hypothesis, we obtained quantitative measures of stride-to-stride variability of gait cycle timing in subjects with PD (n = 15), HD (n = 20), and disease-free controls (n = 16). All measures of gait variability were significantly increased in PD and HD. In subjects with PD and HD, gait variability measures were two and three times that observed in control subjects, respectively. The degree of gait variability correlated with disease severity. In contrast, gait speed was significantly lower in PD, but not in HD, and average gait cycle duration and the time spent in many subphases of the gait cycle were similar in control subjects, HD subjects, and PD subjects. These findings are consistent with a differential control of gait variability, speed, and average gait cycle timing that may have implications for understanding the role of the basal ganglia in locomotor control and for quantitatively assessing gait in clinical settings.

  2. Differentiation of sCJD and vCJD forms by automated analysis of basal ganglia intensity distribution in multisequence MRI of the brain--definition and evaluation of new MRI-based ratios.

    PubMed

    Linguraru, Marius George; Ayache, Nicholas; Bardinet, Eric; Ballester, Miguel Angel González; Galanaud, Damien; Haïk, Stéphane; Faucheux, Baptiste; Hauw, Jean-Jacques; Cozzone, Patrick; Dormont, Didier; Brandel, Jean-Philippe

    2006-08-01

    We present a method for the analysis of basal ganglia (including the thalamus) for accurate detection of human spongiform encephalopathy in multisequence magnetic resonance imaging (MRI) of the brain. One common feature of most forms of prion protein diseases is the appearance of hyperintensities in the deep grey matter area of the brain in T2-weighted magnetic resonance (MR) images. We employ T1, T2, and Flair-T2 MR sequences for the detection of intensity deviations in the internal nuclei. First, the MR data are registered to a probabilistic atlas and normalized in intensity. Then smoothing is applied with edge enhancement. The segmentation of hyperintensities is performed using a model of the human visual system. For more accurate results, a priori anatomical data from a segmented atlas are employed to refine the registration and remove false positives. The results are robust over the patient data and in accordance with the clinical ground truth. Our method further allows the quantification of intensity distributions in basal ganglia. The caudate nuclei are highlighted as main areas of diagnosis of sporadic Creutzfeldt-Jakob Disease (sCJD), in agreement with the histological data. The algorithm permitted the classification of the intensities of abnormal signals in sCJD patient FLAIR images with a higher hypersignal in caudate nuclei (10/10) and putamen (6/10) than in thalami. Defining normalized MRI measures of the intensity relations between the internal grey nuclei of patients, we robustly differentiate sCJD and variant CJD (vCJD) patients, in an attempt to create an automatic classification tool of human spongiform encephalopathies.

  3. Adenosine A2A Receptor in the Monkey Basal Ganglia: Ultrastructural Localization and Colocalization With the Metabotropic Glutamate Receptor 5 in the Striatum

    PubMed Central

    Bogenpohl, James W.; Ritter, Stefanie L.; Hall, Randy A.; Smith, Yoland

    2012-01-01

    The adenosine A2A receptor (A2AR) is a potential drug target for the treatment of Parkinson’s disease and other neurological disorders. In rodents, the therapeutic efficacy of A2AR modulation is improved by concomitant modulation of the metabotropic glutamate receptor 5 (mGluR5). To elucidate the anatomical substrate(s) through which these therapeutic benefits could be mediated, pre-embedding electron microscopy immunohistochemistry was used to conduct a detailed, quantitative ultrastructural analysis of A2AR localization in the primate basal ganglia and to assess the degree of A2AR/mGluR5 colocalization in the striatum. A2AR immunoreactivity was found at the highest levels in the striatum and external globus pallidus (GPe). However, the monkey, but not the rat, substantia nigra pars reticulata (SNr) also harbored a significant level of neuropil A2AR immunoreactivity. At the electron microscopic level, striatal A2AR labeling was most commonly localized in postsynaptic elements (58% ± 3% of labeled elements), whereas, in the GPe and SNr, the labeling was mainly presynaptic (71% ± 5%) or glial (27% ± 6%). In both striatal and pallidal structures, putative inhibitory and excitatory terminals displayed A2AR immunoreactivity. Striatal A2AR/mGluR5 colocalization was commonly found; 60–70% of A2AR-immunoreactive dendrites or spines in the monkey striatum coexpress mGluR5. These findings provide the first detailed account of the ultrastructural localization of A2AR in the primate basal ganglia and demonstrate that A2AR and mGluR5 are located to interact functionally in dendrites and spines of striatal neurons. Together, these data foster a deeper understanding of the substrates through which A2AR could regulate primate basal ganglia function and potentially mediate its therapeutic effects in parkinsonism. PMID:21858817

  4. Basal Ganglia Outputs Map Instantaneous Position Coordinates during Behavior

    PubMed Central

    Barter, Joseph W.; Li, Suellen; Sukharnikova, Tatyana; Rossi, Mark A.; Bartholomew, Ryan A.

    2015-01-01

    The basal ganglia (BG) are implicated in many movement disorders, yet how they contribute to movement remains unclear. Using wireless in vivo recording, we measured BG output from the substantia nigra pars reticulata (SNr) in mice while monitoring their movements with video tracking. The firing rate of most nigral neurons reflected Cartesian coordinates (either x- or y-coordinates) of the animal's head position during movement. The firing rates of SNr neurons are either positively or negatively correlated with the coordinates. Using an egocentric reference frame, four types of neurons can be classified: each type increases firing during movement in a particular direction (left, right, up, down), and decreases firing during movement in the opposite direction. Given the high correlation between the firing rate and the x and y components of the position vector, the movement trajectory can be reconstructed from neural activity. Our results therefore demonstrate a quantitative and continuous relationship between BG output and behavior. Thus, a steady BG output signal from the SNr (i.e., constant firing rate) is associated with the lack of overt movement, when a stable posture is maintained by structures downstream of the BG. Any change in SNr firing rate is associated with a change in position (i.e., movement). We hypothesize that the SNr output quantitatively determines the direction, velocity, and amplitude of voluntary movements. By changing the reference signals to downstream position control systems, the BG can produce transitions in body configurations and initiate actions. PMID:25673860

  5. Identifying enhanced cortico-basal ganglia loops associated with prolonged dance training

    PubMed Central

    Li, Gujing; He, Hui; Huang, Mengting; Zhang, Xingxing; Lu, Jing; Lai, Yongxiu; Luo, Cheng; Yao, Dezhong

    2015-01-01

    Studies have revealed that prolonged, specialized training combined with higher cognitive conditioning induces enhanced brain alternation. In particular, dancers with long-term dance experience exhibit superior motor control and integration with their sensorimotor networks. However, little is known about the functional connectivity patterns of spontaneous intrinsic activities in the sensorimotor network of dancers. Our study examined the functional connectivity density (FCD) of dancers with a mean period of over 10 years of dance training in contrast with a matched non-dancer group without formal dance training using resting-state fMRI scans. FCD was mapped and analyzed, and the functional connectivity (FC) analyses were then performed based on the difference of FCD. Compared to the non-dancers, the dancers exhibited significantly increased FCD in the precentral gyri, postcentral gyri and bilateral putamen. Furthermore, the results of the FC analysis revealed enhanced connections between the middle cingulate cortex and the bilateral putamen and between the precentral and the postcentral gyri. All findings indicated an enhanced functional integration in the cortico-basal ganglia loops that govern motor control and integration in dancers. These findings might reflect improved sensorimotor function for the dancers consequent to long-term dance training. PMID:26035693

  6. Relationship between Contrast Enhancement of the Perivascular Space in the Basal Ganglia and Endolymphatic Volume Ratio.

    PubMed

    Ohashi, Toshio; Naganawa, Shinji; Katagiri, Toshio; Kuno, Kayao

    2018-01-10

    We routinely obtain the endolymphatic hydrops (EH) image using heavily T 2 -weighted three dimensional-fluid attenuated inversion recovery (hT 2 w-3D-FLAIR) imaging at 4 hours after intravenous administration of a single-dose of gadolinium-based contrast media (IV-SD-GBCM). While repeating the examination, we speculated that the contrast enhancement of the perivascular space (PVS) in the basal ganglia might be related to the degree of EH. Therefore, the purpose of this study was to investigate the relationship between the endolymphatic volume ratio (%EL volume ) and the signal intensity of the PVS (SI-PVS). In 20 patients with a suspicion of EH, a heavily T 2 -weighted 3D-turbo spin echo sequence for MR cisternography (MRC) and an hT 2 w-3D-FLAIR as a positive perilymph image (PPI) were obtained at 4 hours after IV-SD-GBCM. The %EL volume of the cochlea and the vestibule were measured on the previously reported HYDROPS2-Mi2 image. The PVS in the basal ganglia was segmented on MRC using a region-growing method. The PVS regions were copied and pasted onto the PPI, and the SI-PVS was measured. The larger value of the right and the left ears was employed as the %EL volume , and the weighted average of both sides was employed as the SI-PVS. The correlation between the %EL volume and the SI-PVS was evaluated. There was a strong negative linear correlation between the %EL volume of the cochlea and the SI-PVS (r = -0.743, P < 0.001); however, there was no significant correlation between the %EL volume of the vestibule and the SI-PVS (r = -0.267, P = 0.256). There was a strong negative correlation between the cochlear %EL volume and the SI-PVS. Contrast enhancement of PVS might be a biomarker of EH.

  7. FROM REINFORCEMENT LEARNING MODELS OF THE BASAL GANGLIA TO THE PATHOPHYSIOLOGY OF PSYCHIATRIC AND NEUROLOGICAL DISORDERS

    PubMed Central

    Maia, Tiago V.; Frank, Michael J.

    2013-01-01

    Over the last decade and a half, reinforcement learning models have fostered an increasingly sophisticated understanding of the functions of dopamine and cortico-basal ganglia-thalamo-cortical (CBGTC) circuits. More recently, these models, and the insights that they afford, have started to be used to understand key aspects of several psychiatric and neurological disorders that involve disturbances of the dopaminergic system and CBGTC circuits. We review this approach and its existing and potential applications to Parkinson’s disease, Tourette’s syndrome, attention-deficit/hyperactivity disorder, addiction, schizophrenia, and preclinical animal models used to screen novel antipsychotic drugs. The approach’s proven explanatory and predictive power bodes well for the continued growth of computational psychiatry and computational neurology. PMID:21270784

  8. Quetiapine responsive catatonia in an autistic patient with comorbid bipolar disorder and idiopathic basal ganglia calcification.

    PubMed

    Ishitobi, Makoto; Kawatani, Masao; Asano, Mizuki; Kosaka, Hirotaka; Goto, Takashi; Hiratani, Michio; Wada, Yuji

    2014-10-01

    Bipolar disorder (BD) has been linked with the manifestation of catatonia in subjects with autism spectrum disorders (ASD). Idiopathic basal ganglia calcification (IBGC) is characterized by movement disorders and various neuropsychiatric disturbances including mood disorder. We present a patient with ASD and IBGC who developed catatonia presenting with prominent dystonic feature caused by comorbid BD, which was treated effectively with quetiapine. In addition to considering the possibility of neurodegenerative disease, careful psychiatric interventions are important to avoid overlooking treatable catatonia associated with BD in cases of ASD presenting with both prominent dystonic features and apparent fluctuation of the mood state. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  9. External pallidal stimulation improves parkinsonian motor signs and modulates neuronal activity throughout the basal ganglia thalamic network.

    PubMed

    Vitek, Jerrold L; Zhang, Jianyu; Hashimoto, Takao; Russo, Gary S; Baker, Kenneth B

    2012-01-01

    Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) and the subthalamic nucleus (STN) are effective for the treatment of advanced Parkinson's disease (PD). We have shown previously that DBS of the external segment of the globus pallidus (GPe) is associated with improvements in parkinsonian motor signs; however, the mechanism of this effect is not known. In this study, we extend our findings on the effect of STN and GPi DBS on neuronal activity in the basal ganglia thalamic network to include GPe DBS using the 1-methyl-4-phenyl-1.2.3.6-tetrahydropyridine (MPTP) monkey model. Stimulation parameters that improved bradykinesia were associated with changes in the pattern and mean discharge rate of neuronal activity in the GPi, STN, and the pallidal [ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)] and cerebellar [ventralis lateralis posterior pars oralis (VPLo)] receiving areas of the motor thalamus. Population post-stimulation time histograms revealed a complex pattern of stimulation-related inhibition and excitation for the GPi and VA/VLo, with a more consistent pattern of inhibition in STN and excitation in VPLo. Mean discharge rate was reduced in the GPi and STN and increased in the VPLo. Effective GPe DBS also reduced bursting in the STN and GPi. These data support the hypothesis that therapeutic DBS activates output from the stimulated structure and changes the temporal pattern of neuronal activity throughout the basal ganglia thalamic network and provide further support for GPe as a potential therapeutic target for DBS in the treatment of PD. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. No evidence of perfusion abnormalities in the basal ganglia of a patient with generalized chorea-ballism and polycythaemia vera: analysis using subtraction SPECT co-registered to MRI.

    PubMed

    Kim, Woojun; Kim, Joong-Seok; Lee, Kwang-Soo; Kim, Yeong-In; Park, Chong-Won; Chung, Yong-An

    2008-10-01

    Polycythaemia vera is a well-known cause of symptomatic chorea, however, the pathophysiology of this correlation remains unclear. We report on a patient with generalized chorea-ballism associated with polycythaemia vera, and we present the findings of 99mTc-hexamethylpropylene amine oxime (HMPAO) SPECT done in both the choreic state and the non-choreic state. The SPECT during both the choreic and the non-choreic states did not reveal any definite perfusion changes in specific regions of the brain, as compared with 6 age-matched controls. In addition, the subtraction SPECT co-registered to MRI (SISCOM) analysis did not show any difference in cerebral blood flow during the choreic and non-choreic states. This result suggests that the basic mechanism of chorea associated with polycythaemia vera does not appear to be associated with a reduction in cerebral perfusion to a specific cerebral area, such as the basal ganglia or its thalamocortical connections.

  11. Effective deep brain stimulation suppresses low-frequency network oscillations in the basal ganglia by regularizing neural firing patterns.

    PubMed

    McConnell, George C; So, Rosa Q; Hilliard, Justin D; Lopomo, Paola; Grill, Warren M

    2012-11-07

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson's disease (PD). The effects of DBS depend strongly on stimulation frequency: high frequencies (>90 Hz) improve motor symptoms, while low frequencies (<50 Hz) are either ineffective or exacerbate symptoms. The neuronal basis for these frequency-dependent effects of DBS is unclear. The effects of different frequencies of STN-DBS on behavior and single-unit neuronal activity in the basal ganglia were studied in the unilateral 6-hydroxydopamine lesioned rat model of PD. Only high-frequency DBS reversed motor symptoms, and the effectiveness of DBS depended strongly on stimulation frequency in a manner reminiscent of its clinical effects in persons with PD. Quantification of single-unit activity in the globus pallidus externa (GPe) and substantia nigra reticulata (SNr) revealed that high-frequency DBS, but not low-frequency DBS, reduced pathological low-frequency oscillations (∼9 Hz) and entrained neurons to fire at the stimulation frequency. Similarly, the coherence between simultaneously recorded pairs of neurons within and across GPe and SNr shifted from the pathological low-frequency band to the stimulation frequency during high-frequency DBS, but not during low-frequency DBS. The changes in firing patterns in basal ganglia neurons were not correlated with changes in firing rate. These results indicate that high-frequency DBS is more effective than low-frequency DBS, not as a result of changes in firing rate, but rather due to its ability to replace pathological low-frequency network oscillations with a regularized pattern of neuronal firing.

  12. Effective deep brain stimulation suppresses low frequency network oscillations in the basal ganglia by regularizing neural firing patterns

    PubMed Central

    McConnell, George C.; So, Rosa Q.; Hilliard, Justin D; Lopomo, Paola; Grill, Warren M.

    2012-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson’s disease (PD). The effects of DBS depend strongly on stimulation frequency: high frequencies (>90Hz) improve motor symptoms, while low frequencies (<50Hz) are either ineffective or exacerbate symptoms. The neuronal basis for these frequency-dependent effects of DBS is unclear. The effects of different frequencies of STN-DBS on behavior and single-unit neuronal activity in the basal ganglia were studied in the unilateral 6-hydroxydopamine lesioned rat model of PD. Only high frequency DBS reversed motor symptoms and the effectiveness of DBS depended strongly on stimulation frequency in a manner reminiscent of its clinical effects in persons with PD. Quantification of single-unit activity in the globus pallidus externa (GPe) and substantia nigra reticulata (SNr) revealed that high frequency DBS, but not low frequency DBS, reduced pathological low frequency oscillations (~9Hz) and entrained neurons to fire at the stimulation frequency. Similarly, the coherence between simultaneously recorded pairs of neurons within and across GPe and SNr shifted from the pathological low frequency band to the stimulation frequency during high frequency DBS, but not during low frequency DBS. The changes in firing patterns in basal ganglia neurons were not correlated with changes in firing rate. These results indicate that high frequency DBS is more effective than low frequency DBS, not as a result of changes in firing rate, but rather due to its ability to replace pathological low frequency network oscillations with a regularized pattern of neuronal firing. PMID:23136407

  13. Prospects for cannabinoid therapies in basal ganglia disorders

    PubMed Central

    Fernández-Ruiz, Javier; Moreno-Martet, Miguel; Rodríguez-Cueto, Carmen; Palomo-Garo, Cristina; Gómez-Cañas, María; Valdeolivas, Sara; Guaza, Carmen; Romero, Julián; Guzmán, Manuel; Mechoulam, Raphael; Ramos, José A

    2011-01-01

    Cannabinoids are promising medicines to slow down disease progression in neurodegenerative disorders including Parkinson's disease (PD) and Huntington's disease (HD), two of the most important disorders affecting the basal ganglia. Two pharmacological profiles have been proposed for cannabinoids being effective in these disorders. On the one hand, cannabinoids like Δ9-tetrahydrocannabinol or cannabidiol protect nigral or striatal neurons in experimental models of both disorders, in which oxidative injury is a prominent cytotoxic mechanism. This effect could be exerted, at least in part, through mechanisms independent of CB1 and CB2 receptors and involving the control of endogenous antioxidant defences. On the other hand, the activation of CB2 receptors leads to a slower progression of neurodegeneration in both disorders. This effect would be exerted by limiting the toxicity of microglial cells for neurons and, in particular, by reducing the generation of proinflammatory factors. It is important to mention that CB2 receptors have been identified in the healthy brain, mainly in glial elements and, to a lesser extent, in certain subpopulations of neurons, and that they are dramatically up-regulated in response to damaging stimuli, which supports the idea that the cannabinoid system behaves as an endogenous neuroprotective system. This CB2 receptor up-regulation has been found in many neurodegenerative disorders including HD and PD, which supports the beneficial effects found for CB2 receptor agonists in both disorders. In conclusion, the evidence reported so far supports that those cannabinoids having antioxidant properties and/or capability to activate CB2 receptors may represent promising therapeutic agents in HD and PD, thus deserving a prompt clinical evaluation. LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21545415

  14. Prospects for cannabinoid therapies in basal ganglia disorders.

    PubMed

    Fernández-Ruiz, Javier; Moreno-Martet, Miguel; Rodríguez-Cueto, Carmen; Palomo-Garo, Cristina; Gómez-Cañas, María; Valdeolivas, Sara; Guaza, Carmen; Romero, Julián; Guzmán, Manuel; Mechoulam, Raphael; Ramos, José A

    2011-08-01

    Cannabinoids are promising medicines to slow down disease progression in neurodegenerative disorders including Parkinson's disease (PD) and Huntington's disease (HD), two of the most important disorders affecting the basal ganglia. Two pharmacological profiles have been proposed for cannabinoids being effective in these disorders. On the one hand, cannabinoids like Δ(9) -tetrahydrocannabinol or cannabidiol protect nigral or striatal neurons in experimental models of both disorders, in which oxidative injury is a prominent cytotoxic mechanism. This effect could be exerted, at least in part, through mechanisms independent of CB(1) and CB(2) receptors and involving the control of endogenous antioxidant defences. On the other hand, the activation of CB(2) receptors leads to a slower progression of neurodegeneration in both disorders. This effect would be exerted by limiting the toxicity of microglial cells for neurons and, in particular, by reducing the generation of proinflammatory factors. It is important to mention that CB(2) receptors have been identified in the healthy brain, mainly in glial elements and, to a lesser extent, in certain subpopulations of neurons, and that they are dramatically up-regulated in response to damaging stimuli, which supports the idea that the cannabinoid system behaves as an endogenous neuroprotective system. This CB(2) receptor up-regulation has been found in many neurodegenerative disorders including HD and PD, which supports the beneficial effects found for CB(2) receptor agonists in both disorders. In conclusion, the evidence reported so far supports that those cannabinoids having antioxidant properties and/or capability to activate CB(2) receptors may represent promising therapeutic agents in HD and PD, thus deserving a prompt clinical evaluation. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  15. The basal ganglia is necessary for learning spectral, but not temporal features of birdsong

    PubMed Central

    Ali, Farhan; Fantana, Antoniu L.; Burak, Yoram; Ölveczky, Bence P.

    2013-01-01

    Executing a motor skill requires the brain to control which muscles to activate at what times. How these aspects of control - motor implementation and timing - are acquired, and whether the learning processes underlying them differ, is not well understood. To address this we used a reinforcement learning paradigm to independently manipulate both spectral and temporal features of birdsong, a complex learned motor sequence, while recording and perturbing activity in underlying circuits. Our results uncovered a striking dissociation in how neural circuits underlie learning in the two domains. The basal ganglia was required for modifying spectral, but not temporal structure. This functional dissociation extended to the descending motor pathway, where recordings from a premotor cortex analogue nucleus reflected changes to temporal, but not spectral structure. Our results reveal a strategy in which the nervous system employs different and largely independent circuits to learn distinct aspects of a motor skill. PMID:24075977

  16. A Mathematical Model of Levodopa Medication Effect on Basal Ganglia in Parkinson's Disease: An Application to the Alternate Finger Tapping Task.

    PubMed

    Baston, Chiara; Contin, Manuela; Calandra Buonaura, Giovanna; Cortelli, Pietro; Ursino, Mauro

    2016-01-01

    Malfunctions in the neural circuitry of the basal ganglia (BG), induced by alterations in the dopaminergic system, are responsible for an array of motor disorders and milder cognitive issues in Parkinson's disease (PD). Recently Baston and Ursino (2015a) presented a new neuroscience mathematical model aimed at exploring the role of basal ganglia in action selection. The model is biologically inspired and reproduces the main BG structures and pathways, modeling explicitly both the dopaminergic and the cholinergic system. The present work aims at interfacing this neurocomputational model with a compartmental model of levodopa, to propose a general model of medicated Parkinson's disease. Levodopa effect on the striatum was simulated with a two-compartment model of pharmacokinetics in plasma joined with a motor effect compartment. The latter is characterized by the levodopa removal rate and by a sigmoidal relationship (Hill law) between concentration and effect. The main parameters of this relationship are saturation, steepness, and the half-maximum concentration. The effect of levodopa is then summed to a term representing the endogenous dopamine effect, and is used as an external input for the neurocomputation model; this allows both the temporal aspects of medication and the individual patient characteristics to be simulated. The frequency of alternate tapping is then used as the outcome of the whole model, to simulate effective clinical scores. Pharmacokinetic-pharmacodynamic modeling was preliminary performed on data of six patients with Parkinson's disease (both "stable" and "wearing-off" responders) after levodopa standardized oral dosing over 4 h. Results show that the model is able to reproduce the temporal profiles of levodopa in plasma and the finger tapping frequency in all patients, discriminating between different patterns of levodopa motor response. The more influential parameters are the Hill coefficient, related with the slope of the effect sigmoidal

  17. A Mathematical Model of Levodopa Medication Effect on Basal Ganglia in Parkinson's Disease: An Application to the Alternate Finger Tapping Task

    PubMed Central

    Baston, Chiara; Contin, Manuela; Calandra Buonaura, Giovanna; Cortelli, Pietro; Ursino, Mauro

    2016-01-01

    Malfunctions in the neural circuitry of the basal ganglia (BG), induced by alterations in the dopaminergic system, are responsible for an array of motor disorders and milder cognitive issues in Parkinson's disease (PD). Recently Baston and Ursino (2015a) presented a new neuroscience mathematical model aimed at exploring the role of basal ganglia in action selection. The model is biologically inspired and reproduces the main BG structures and pathways, modeling explicitly both the dopaminergic and the cholinergic system. The present work aims at interfacing this neurocomputational model with a compartmental model of levodopa, to propose a general model of medicated Parkinson's disease. Levodopa effect on the striatum was simulated with a two-compartment model of pharmacokinetics in plasma joined with a motor effect compartment. The latter is characterized by the levodopa removal rate and by a sigmoidal relationship (Hill law) between concentration and effect. The main parameters of this relationship are saturation, steepness, and the half-maximum concentration. The effect of levodopa is then summed to a term representing the endogenous dopamine effect, and is used as an external input for the neurocomputation model; this allows both the temporal aspects of medication and the individual patient characteristics to be simulated. The frequency of alternate tapping is then used as the outcome of the whole model, to simulate effective clinical scores. Pharmacokinetic-pharmacodynamic modeling was preliminary performed on data of six patients with Parkinson's disease (both “stable” and “wearing-off” responders) after levodopa standardized oral dosing over 4 h. Results show that the model is able to reproduce the temporal profiles of levodopa in plasma and the finger tapping frequency in all patients, discriminating between different patterns of levodopa motor response. The more influential parameters are the Hill coefficient, related with the slope of the effect

  18. Hereditary haemochromatosis: a case of iron accumulation in the basal ganglia associated with a parkinsonian syndrome.

    PubMed Central

    Nielsen, J E; Jensen, L N; Krabbe, K

    1995-01-01

    Hereditary haemochromatosis is characterised by excessive parenchymal iron deposition, particularly in the liver. Usually hereditary haemochromatosis is not associated with neurological symptoms and iron deposition in the brain has not previously been described as a pathological phenomenon. A patient is reported with hereditary haemochromatosis and a syndrome of dementia, dysarthria, a slowly progressive gait disturbance, imbalance, muscle weakness, rigidity, bradykinesia, tremor, ataxia, and dyssynergia. The findings on MRI of a large signal decrease in the basal ganglia, consistent with excessive iron accumulation, indicate a causal relation to the symptoms. Although the neurological symptoms did not improve in our patient, hereditary haemochromatosis should be considered in the differential diagnosis of parkinsonian syndromes, because complications of iron induced organ injury may be prevented by phlebotomy. Images PMID:7673967

  19. Long-term increase in coherence between the basal ganglia and motor cortex after asphyxial cardiac arrest and resuscitation in developing rats.

    PubMed

    Aravamuthan, Bhooma R; Shoykhet, Michael

    2015-10-01

    The basal ganglia are vulnerable to injury during cardiac arrest. Movement disorders are a common morbidity in survivors. Yet, neuronal motor network changes post-arrest remain poorly understood. We compared function of the motor network in adult rats that, during postnatal week 3, underwent 9.5 min of asphyxial cardiac arrest (n = 9) or sham intervention (n = 8). Six months after injury, we simultaneously recorded local field potentials (LFP) from the primary motor cortex (MCx) and single neuron firing and LFP from the rat entopeduncular nucleus (EPN), which corresponds to the primate globus pallidus pars interna. Data were analyzed for firing rates, power, and coherence between MCx and EPN spike and LFP activity. Cardiac arrest survivors display chronic motor deficits. EPN firing rate is lower in cardiac arrest survivors (19.5 ± 2.4 Hz) compared with controls (27.4 ± 2.7 Hz; P < 0.05). Cardiac arrest survivors also demonstrate greater coherence between EPN single neurons and MCx LFP (3-100 Hz; P < 0.001). This increased coherence indicates abnormal synchrony in the neuronal motor network after cardiac arrest. Increased motor network synchrony is thought to be antikinetic in primary movement disorders. Characterization of motor network synchrony after cardiac arrest may help guide management of post-hypoxic movement disorders.

  20. Song Selectivity in the Pallial-Basal Ganglia Song Circuit of Zebra Finches Raised Without Tutor Song Exposure

    PubMed Central

    Kojima, Satoshi; Doupe, Allison J.

    2008-01-01

    Acoustic experience critically influences auditory cortical development as well as emergence of highly selective auditory neurons in the songbird sensorimotor circuit. In adult zebra finches, these “song-selective” neurons respond better to the bird's own song (BOS) than to songs of other conspecifics. Birds learn their songs by memorizing a tutor's song and then matching auditory feedback of their voice to the tutor song memory. Song-selective neurons in the pallial-basal ganglia circuit called the anterior forebrain pathway (AFP) reflect the development of BOS. However, during learning, they also respond strongly to tutor song and are compromised in their adult selectivity when birds are prevented from matching BOS to tutor, suggesting that selectivity depends on tutor song learning as well as sensorimotor matching of BOS feedback to the tutor song memory. We examined the contribution of sensory learning of tutor song to song selectivity by recording from AFP neurons in birds reared without exposure to adult conspecifics. We found that AFP neurons in these “isolate” birds had highly tuned responses to isolate BOS. The selectivity was as high, and in the striato-pallidal nucleus Area X, even higher than that in normal birds, due to abnormally weak responsiveness to conspecific song. These results demonstrate that sensory learning of tutor song is not necessary for BOS tuning of AFP neurons. Because isolate birds develop their song via sensorimotor learning, our data further illustrate the importance of individual sensorimotor learning for song selectivity and provide insight into possible functions of song-selective neurons. PMID:17625059

  1. Viral vector-based tools advance knowledge of basal ganglia anatomy and physiology

    PubMed Central

    Sizemore, Rachel J.; Seeger-Armbruster, Sonja; Hughes, Stephanie M.

    2016-01-01

    Viral vectors were originally developed to deliver genes into host cells for therapeutic potential. However, viral vector use in neuroscience research has increased because they enhance interpretation of the anatomy and physiology of brain circuits compared with conventional tract tracing or electrical stimulation techniques. Viral vectors enable neuronal or glial subpopulations to be labeled or stimulated, which can be spatially restricted to a single target nucleus or pathway. Here we review the use of viral vectors to examine the structure and function of motor and limbic basal ganglia (BG) networks in normal and pathological states. We outline the use of viral vectors, particularly lentivirus and adeno-associated virus, in circuit tracing, optogenetic stimulation, and designer drug stimulation experiments. Key studies that have used viral vectors to trace and image pathways and connectivity at gross or ultrastructural levels are reviewed. We explain how optogenetic stimulation and designer drugs used to modulate a distinct pathway and neuronal subpopulation have enhanced our mechanistic understanding of BG function in health and pathophysiology in disease. Finally, we outline how viral vector technology may be applied to neurological and psychiatric conditions to offer new treatments with enhanced outcomes for patients. PMID:26888111

  2. Relationship between Contrast Enhancement of the Perivascular Space in the Basal Ganglia and Endolymphatic Volume Ratio

    PubMed Central

    Ohashi, Toshio; Naganawa, Shinji; Katagiri, Toshio; Kuno, Kayao

    2018-01-01

    Purpose: We routinely obtain the endolymphatic hydrops (EH) image using heavily T2-weighted three dimensional-fluid attenuated inversion recovery (hT2w-3D-FLAIR) imaging at 4 hours after intravenous administration of a single-dose of gadolinium-based contrast media (IV-SD-GBCM). While repeating the examination, we speculated that the contrast enhancement of the perivascular space (PVS) in the basal ganglia might be related to the degree of EH. Therefore, the purpose of this study was to investigate the relationship between the endolymphatic volume ratio (%ELvolume) and the signal intensity of the PVS (SI-PVS). Materials and Methods: In 20 patients with a suspicion of EH, a heavily T2-weighted 3D-turbo spin echo sequence for MR cisternography (MRC) and an hT2w-3D-FLAIR as a positive perilymph image (PPI) were obtained at 4 hours after IV-SD-GBCM. The %ELvolume of the cochlea and the vestibule were measured on the previously reported HYDROPS2-Mi2 image. The PVS in the basal ganglia was segmented on MRC using a region-growing method. The PVS regions were copied and pasted onto the PPI, and the SI-PVS was measured. The larger value of the right and the left ears was employed as the %ELvolume, and the weighted average of both sides was employed as the SI-PVS. The correlation between the %ELvolume and the SI-PVS was evaluated. Result: There was a strong negative linear correlation between the %ELvolume of the cochlea and the SI-PVS (r = −0.743, P < 0.001); however, there was no significant correlation between the %ELvolume of the vestibule and the SI-PVS (r = −0.267, P = 0.256). Conclusion: There was a strong negative correlation between the cochlear %ELvolume and the SI-PVS. Contrast enhancement of PVS might be a biomarker of EH. PMID:28592709

  3. Eyes on MEGDEL: distinctive basal ganglia involvement in dystonia deafness syndrome.

    PubMed

    Wortmann, Saskia B; van Hasselt, Peter M; Barić, Ivo; Burlina, Alberto; Darin, Niklas; Hörster, Friederike; Coker, Mahmut; Ucar, Sema Kalkan; Krumina, Zita; Naess, Karin; Ngu, Lock H; Pronicka, Ewa; Riordan, Gilian; Santer, Rene; Wassmer, Evangeline; Zschocke, Johannes; Schiff, Manuel; de Meirleir, Linda; Alowain, Mohammed A; Smeitink, Jan A M; Morava, Eva; Kozicz, Tamas; Wevers, Ron A; Wolf, Nicole I; Willemsen, Michel A

    2015-04-01

    Pediatric movement disorders are still a diagnostic challenge, as many patients remain without a (genetic) diagnosis. Magnetic resonance imaging (MRI) pattern recognition can lead to the diagnosis. MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome MIM #614739) is a clinically and biochemically highly distinctive dystonia deafness syndrome accompanied by 3-methylglutaconic aciduria, severe developmental delay, and progressive spasticity. Mutations are found in SERAC1, encoding a phosphatidylglycerol remodeling enzyme essential for both mitochondrial function and intracellular cholesterol trafficking. Based on the homogenous phenotype, we hypothesized an accordingly characteristic MRI pattern. A total of 43 complete MRI studies of 30 patients were systematically reevaluated. All patients presented a distinctive brain MRI pattern with five characteristic disease stages affecting the basal ganglia, especially the putamen. In stage 1, T2 signal changes of the pallidum are present. In stage 2, swelling of the putamen and caudate nucleus is seen. The dorsal putamen contains an "eye" that shows no signal alteration and (thus) seems to be spared during this stage of the disease. It later increases, reflecting progressive putaminal involvement. This "eye" was found in all patients with MEGDEL syndrome during a specific age range, and has not been reported in other disorders, making it pathognomonic for MEDGEL and allowing diagnosis based on MRI findings. Georg Thieme Verlag KG Stuttgart · New York.

  4. Neural Dynamics of Autistic Repetitive Behaviors and Fragile X Syndrome: Basal Ganglia Movement Gating and mGluR-Modulated Adaptively Timed Learning.

    PubMed

    Grossberg, Stephen; Kishnan, Devika

    2018-01-01

    This article develops the iSTART neural model that proposes how specific imbalances in cognitive, emotional, timing, and motor processes that involve brain regions like prefrontal cortex, temporal cortex, amygdala, hypothalamus, hippocampus, and cerebellum may interact together to cause behavioral symptoms of autism. These imbalances include underaroused emotional depression in the amygdala/hypothalamus, learning of hyperspecific recognition categories that help to cause narrowly focused attention in temporal and prefrontal cortices, and breakdowns of adaptively timed motivated attention and motor circuits in the hippocampus and cerebellum. The article expands the model's explanatory range by, first, explaining recent data about Fragile X syndrome (FXS), mGluR, and trace conditioning; and, second, by explaining distinct causes of stereotyped behaviors in individuals with autism. Some of these stereotyped behaviors, such as an insistence on sameness and circumscribed interests, may result from imbalances in the cognitive and emotional circuits that iSTART models. These behaviors may be ameliorated by operant conditioning methods. Other stereotyped behaviors, such as repetitive motor behaviors, may result from imbalances in how the direct and indirect pathways of the basal ganglia open or close movement gates, respectively. These repetitive behaviors may be ameliorated by drugs that augment D2 dopamine receptor responses or reduce D1 dopamine receptor responses. The article also notes the ubiquitous role of gating by basal ganglia loops in regulating all the functions that iSTART models.

  5. Light-Induced Alterations in Basil Ganglia Kynurenic Acid Levels

    NASA Technical Reports Server (NTRS)

    Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.; Orr, M. C.

    1997-01-01

    The metabolic synthesis, release and breakdown of several known CNS neurotransmitters have been shown to follow a circadian pattern entrained to the environmental light/dark cycle. The levels of excitatory amino acid (EAA) transmitters such as glutamate, have been shown to vary with environmental lighting conditions. Kynurenic Acid (KA), an endogenous tryptophan metabolite and glutamate receptor antagonist, has been reported to have neuroprotective effects against EAA-induced excitotoxic cell damage. Changes in KA's activity within the mammalian basal ganglia has been proposed as being contributory to neurotoxicity in Huntington's Disease. It is not known whether CNS KA levels follow a circadian pattern or exhibit light-induced fluctuations. However, because the symptoms of certain degenerative motor disorders seem to fluctuate with daily 24 hour rhythm, we initiated studies to determine if basal ganglia KA were influenced by the daily light/dark cycle and could influence motor function. Therefore in this study, HPLC-EC was utilized to determine if basal ganglia KA levels in tissue extracts from adult male Long-Evans rats (200-250g) entrained to 24 and 48 hours constant light and dark conditions, respectively. Samples were taken one hour before the onset of the subjective day and one hour prior to the onset of the subjective night in order to detect possible phase differences in KA levels and to allow for accumulation of factors expressed in association with the light or dark phase. Data analysis revealed that KA levels in the basal ganglia vary with environmental lighting conditions; being elevated generally during the dark. Circadian phase differences in KA levels were also evident during the subjective night and subjective day, respectively. Results from these studies are discussed with respect to potential cyclic changes in neuronal susceptibility to excitotoxic damage during the daily 24 hour cycle and its possible relevance to future therapeutic approaches in

  6. Bilateral Functional Connectivity of the Basal Ganglia in Patients with Parkinson’s Disease and Its Modulation by Dopaminergic Treatment

    PubMed Central

    Little, Simon; Tan, Huiling; Anzak, Anam; Pogosyan, Alek; Kühn, Andrea; Brown, Peter

    2013-01-01

    Parkinson’s disease is characterised by excessive subcortical beta oscillations. However, little is known about the functional connectivity of the two basal ganglia across hemispheres and specifically the role beta plays in this. We recorded local field potentials from the subthalamic nucleus bilaterally in 23 subjects with Parkinson’s disease at rest, on and off medication. We found suppression of low beta power in response to levodopa (t22 = −4.4, p<0.001). There was significant coherence between the two sides in the beta range in 19 of the subjects. Coherence was selectively attenuated in the low beta range following levodopa (t22 = −2.7; p = 0.01). We also separately analysed amplitude co-modulation and phase synchronisation in the beta band and found significant amplitude co-modulation and phase locking values in 17 and 16 subjects respectively, off medication. There was a dissociable effect of levodopa on these measures, with a significant suppression only in low beta phase locking value (t22 = −2.8, p = 0.01) and not amplitude co-modulation. The absolute mean values of amplitude co-modulation (0.40±0.03) and phase synchronisation (0.29±0.02) off medication were, however, relatively low, suggesting that the two basal ganglia networks may have to be approached separately with independent sensing and stimulation during adaptive deep brain stimulation. In addition, our findings highlight the functional distinction between the lower and upper beta frequency ranges and between amplitude co-modulation and phase synchronization across subthalamic nuclei. PMID:24376574

  7. Viral vector-based tools advance knowledge of basal ganglia anatomy and physiology.

    PubMed

    Sizemore, Rachel J; Seeger-Armbruster, Sonja; Hughes, Stephanie M; Parr-Brownlie, Louise C

    2016-04-01

    Viral vectors were originally developed to deliver genes into host cells for therapeutic potential. However, viral vector use in neuroscience research has increased because they enhance interpretation of the anatomy and physiology of brain circuits compared with conventional tract tracing or electrical stimulation techniques. Viral vectors enable neuronal or glial subpopulations to be labeled or stimulated, which can be spatially restricted to a single target nucleus or pathway. Here we review the use of viral vectors to examine the structure and function of motor and limbic basal ganglia (BG) networks in normal and pathological states. We outline the use of viral vectors, particularly lentivirus and adeno-associated virus, in circuit tracing, optogenetic stimulation, and designer drug stimulation experiments. Key studies that have used viral vectors to trace and image pathways and connectivity at gross or ultrastructural levels are reviewed. We explain how optogenetic stimulation and designer drugs used to modulate a distinct pathway and neuronal subpopulation have enhanced our mechanistic understanding of BG function in health and pathophysiology in disease. Finally, we outline how viral vector technology may be applied to neurological and psychiatric conditions to offer new treatments with enhanced outcomes for patients. Copyright © 2016 the American Physiological Society.

  8. Regional atrophy of the basal ganglia and thalamus in idiopathic generalized epilepsy.

    PubMed

    Du, Hanjian; Zhang, Yuanchao; Xie, Bing; Wu, Nan; Wu, Guocai; Wang, Jian; Jiang, Tianzi; Feng, Hua

    2011-04-01

    To determine the regional changes in the shapes of subcortical structures in idiopathic generalized epilepsy using a vertex-based analysis method. Earlier studies found that gray matter volume in the frontal, parietal, and temporal lobes is significantly altered in idiopathic generalized epilepsy (IGE). Research has indicated that a relationship exists between the brain's subcortical structures and epilepsy. However, little is known about possible changes in the subcortical structures in IGE. This study aims to determine the changes in the shape of subcortical structures in IGE using vertex analysis. Fourteen male patients with IGE and 28 age- and sex-matched healthy controls were included in this study, which used high-resolution magnetic resonance imaging. We performed a vertex-based shape analysis, in which we compared patients with IGE with the controls, on the subcortical structures that we had obtained from the MRI data. Statistical analysis showed significant regional atrophy in the left thalamus, left putamen and bilateral globus pallidus in patients with IGE. These results indicate that regional atrophy of the basal ganglia and the thalamus may be related to seizure disorder. In the future, these findings may prove useful for choosing new therapeutic regimens. Copyright © 2011 Wiley-Liss, Inc.

  9. Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive

    PubMed Central

    Fiore, Vincenzo G.; Rigoli, Francesco; Stenner, Max-Philipp; Zaehle, Tino; Hirth, Frank; Heinze, Hans-Jochen; Dolan, Raymond J.

    2016-01-01

    Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson’s disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model. PMID:27004463

  10. Sonographic Alteration of Basal Ganglia in Different Forms of Primary Focal Dystonia: A Cross-sectional Study

    PubMed Central

    Zhang, Ying; Zhang, Ying-Chun; Sheng, Yu-Jing; Chen, Xiao-Fang; Wang, Cai-Shan; Ma, Qi; Chen, Han-Bing; Yu, Li-Fang; Mao, Cheng-Jie; Xiong, Kang-Ping; Luo, Wei-Feng; Liu, Chun-Feng

    2016-01-01

    Background: Few studies have addressed whether abnormalities in the lenticular nucleus (LN) are characteristic transcranial sonography (TCS) echo features in patients with primary dystonia. This study aimed to explore alterations in the basal ganglia in different forms of primary focal dystonia. Methods: cross-sectional observational study was performed between December 2013 and December 2014 in 80 patients with different forms of primary focal dystonia and 55 neurologically normal control subjects. TCS was performed in patients and control subjects. Multiple comparisons of multiple rates were used to compare LN hyperechogenicity ratios between control and patient groups. Results: Thirteen individuals were excluded due to poor temporal bone windows, and two subjects were excluded due to disagreement in evaluation by sonologists. Totally, 70 patients (cervical dystonia, n = 30; blepharospasm, n = 30; oromandibular dystonia, n = 10) and 50 normal controls were included in the final analysis. LN hyperechogenicity was observed in 51% (36/70) of patients with primary focal dystonia, compared with 12% (6/50) of controls (P < 0.001). Substantia nigra hyperechogenicity did not differ between the two groups. LN hyperechogenicity was observed in 73% (22/30) of patients with cervical dystonia, a greater prevalence than in patients with blepharospasm (33%, 10/30, P = 0.002) and oromandibular dystonia (40%, 4/10, P = 0.126). LN hyperechogenicity was more frequently observed in patients with cervical dystonia compared with controls (73% vs. 12%, P < 0.001); however, no significant difference was detected in patients with blepharospasm (33% vs. 12%, P = 0.021) or oromandibular dystonia (40% vs. 12%, P = 0.088). Conclusions: LN hyperechogenicity is more frequently observed in patients with primary focal dystonia than in controls. It does not appear to be a characteristic TCS echo feature in patients with blepharospasm or oromandibular dystonia. PMID:27064039

  11. Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study.

    PubMed

    Simonyan, Kristina; Ludlow, Christy L

    2010-11-01

    Spasmodic dysphonia (SD) is a task-specific focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speaking. Our aim was to identify symptom-specific functional brain activation abnormalities in adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD). Both SD groups showed increased activation extent in the primary sensorimotor cortex, insula, and superior temporal gyrus during symptomatic and asymptomatic tasks and decreased activation extent in the basal ganglia, thalamus, and cerebellum during asymptomatic tasks. Increased activation intensity in SD patients was found only in the primary somatosensory cortex during symptomatic voice production, which showed a tendency for correlation with ADSD symptoms. Both SD groups had lower correlation of activation intensities between the primary motor and sensory cortices and additional correlations between the basal ganglia, thalamus, and cerebellum during symptomatic and asymptomatic tasks. Compared with ADSD patients, ABSD patients had larger activation extent in the primary sensorimotor cortex and ventral thalamus during symptomatic task and in the inferior temporal cortex and cerebellum during symptomatic and asymptomatic voice production. The primary somatosensory cortex shows consistent abnormalities in activation extent, intensity, correlation with other brain regions, and symptom severity in SD patients and, therefore, may be involved in the pathophysiology of SD.

  12. Abnormal Activation of the Primary Somatosensory Cortex in Spasmodic Dysphonia: An fMRI Study

    PubMed Central

    Ludlow, Christy L.

    2010-01-01

    Spasmodic dysphonia (SD) is a task-specific focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speaking. Our aim was to identify symptom-specific functional brain activation abnormalities in adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD). Both SD groups showed increased activation extent in the primary sensorimotor cortex, insula, and superior temporal gyrus during symptomatic and asymptomatic tasks and decreased activation extent in the basal ganglia, thalamus, and cerebellum during asymptomatic tasks. Increased activation intensity in SD patients was found only in the primary somatosensory cortex during symptomatic voice production, which showed a tendency for correlation with ADSD symptoms. Both SD groups had lower correlation of activation intensities between the primary motor and sensory cortices and additional correlations between the basal ganglia, thalamus, and cerebellum during symptomatic and asymptomatic tasks. Compared with ADSD patients, ABSD patients had larger activation extent in the primary sensorimotor cortex and ventral thalamus during symptomatic task and in the inferior temporal cortex and cerebellum during symptomatic and asymptomatic voice production. The primary somatosensory cortex shows consistent abnormalities in activation extent, intensity, correlation with other brain regions, and symptom severity in SD patients and, therefore, may be involved in the pathophysiology of SD. PMID:20194686

  13. A reverse engineering algorithm for neural networks, applied to the subthalamopallidal network of basal ganglia.

    PubMed

    Floares, Alexandru George

    2008-01-01

    Modeling neural networks with ordinary differential equations systems is a sensible approach, but also very difficult. This paper describes a new algorithm based on linear genetic programming which can be used to reverse engineer neural networks. The RODES algorithm automatically discovers the structure of the network, including neural connections, their signs and strengths, estimates its parameters, and can even be used to identify the biophysical mechanisms involved. The algorithm is tested on simulated time series data, generated using a realistic model of the subthalamopallidal network of basal ganglia. The resulting ODE system is highly accurate, and results are obtained in a matter of minutes. This is because the problem of reverse engineering a system of coupled differential equations is reduced to one of reverse engineering individual algebraic equations. The algorithm allows the incorporation of common domain knowledge to restrict the solution space. To our knowledge, this is the first time a realistic reverse engineering algorithm based on linear genetic programming has been applied to neural networks.

  14. [Mineralization of the basal ganglia as the supposed cause of poor tolerance of zuclopenthixol in a patient with long-term untreated paranoid schizophrenia].

    PubMed

    Wichowicz, Hubert M; Wilkowska, Alina; Banecka-Majkutewicz, Zyta; Kummer, Łukasz; Konarzewska, Joanna; Raczak, Alicja

    2013-01-01

    Formations described as intracranial calcifications can appear in the course of diseases of the central nervous system, other systems and organs (e.g. endocrine), but also as a disorder of idiopathic character. They are frequently located in subcortical nuclei and usually constitute an incidental finding. This report presents the case of a patient suffering from paranoid schizophrenia for approximately 40 years, who did not agree to any treatment and was hospitalized against her will because she was the threat to the lives of others. She was treated with zuklopentixol resulting in positive symptoms reduction and considerable improvement in social functioning. Unfortunately neurological symptoms appeared: bradykinesis, rigidity--of the type of the lead pipe, balance, posture and gait abnormalities, disturbances in precise hands movements, double-sided Rossolimo's sign, plantar reflex without the participation of the big toe on the left. Neuroimaging studies have demonstrated changes in the form of lenticular nuclei calcification and reduction of signal intensity in posterior parts of both putamens. Neurological symptoms decreased significantly after switching to atypical neuroleptic (olanzapine), and the patient did not require any additional treatment. Mineralization of the basal ganglia can often be associated with psychiatric disorders and it shouldn't be neglected because it can require modification of pharmacotherapy or additional neurological treatment.

  15. Focal dystonia secondary to cavernous angioma of the basal ganglia: case report and review of the literature.

    PubMed

    Lorenzana, L; Cabezudo, J M; Porras, L F; Polaina, M; Rodriguez-Sanchez, J A; Garcia-Yagüe, L M

    1992-12-01

    The case of a young woman with focal dystonia of the hand due to a cavernous angioma of the basal ganglia is presented. The lesion involved the anterior third of the lentiform nucleus and a large portion of white matter anterior to this nucleus and lateral to the head of the caudate, as shown by magnetic resonance imaging; it was completely removed through a computed tomography-assisted stereotactic craniotomy by microsurgical technique, resulting in the cure of the patient. These facts support the pathophysiological hypothesis of a disruption of the striatopallidothalamic projection to the premotor cortex as the cause of symptomatic dystonia. A review of the reported cases of cavernous angiomas of the deep cerebral gray nuclei shows that this is the first case of cavernous angioma associated with movement disorder.

  16. A direct GABAergic output from the basal ganglia to frontal cortex

    PubMed Central

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

    2014-01-01

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

  17. Believer-Skeptic Meets Actor-Critic: Rethinking the Role of Basal Ganglia Pathways during Decision-Making and Reinforcement Learning.

    PubMed

    Dunovan, Kyle; Verstynen, Timothy

    2016-01-01

    The flexibility of behavioral control is a testament to the brain's capacity for dynamically resolving uncertainty during goal-directed actions. This ability to select actions and learn from immediate feedback is driven by the dynamics of basal ganglia (BG) pathways. A growing body of empirical evidence conflicts with the traditional view that these pathways act as independent levers for facilitating (i.e., direct pathway) or suppressing (i.e., indirect pathway) motor output, suggesting instead that they engage in a dynamic competition during action decisions that computationally captures action uncertainty. Here we discuss the utility of encoding action uncertainty as a dynamic competition between opposing control pathways and provide evidence that this simple mechanism may have powerful implications for bridging neurocomputational theories of decision making and reinforcement learning.

  18. Neural Dynamics of Autistic Repetitive Behaviors and Fragile X Syndrome: Basal Ganglia Movement Gating and mGluR-Modulated Adaptively Timed Learning

    PubMed Central

    Grossberg, Stephen; Kishnan, Devika

    2018-01-01

    This article develops the iSTART neural model that proposes how specific imbalances in cognitive, emotional, timing, and motor processes that involve brain regions like prefrontal cortex, temporal cortex, amygdala, hypothalamus, hippocampus, and cerebellum may interact together to cause behavioral symptoms of autism. These imbalances include underaroused emotional depression in the amygdala/hypothalamus, learning of hyperspecific recognition categories that help to cause narrowly focused attention in temporal and prefrontal cortices, and breakdowns of adaptively timed motivated attention and motor circuits in the hippocampus and cerebellum. The article expands the model’s explanatory range by, first, explaining recent data about Fragile X syndrome (FXS), mGluR, and trace conditioning; and, second, by explaining distinct causes of stereotyped behaviors in individuals with autism. Some of these stereotyped behaviors, such as an insistence on sameness and circumscribed interests, may result from imbalances in the cognitive and emotional circuits that iSTART models. These behaviors may be ameliorated by operant conditioning methods. Other stereotyped behaviors, such as repetitive motor behaviors, may result from imbalances in how the direct and indirect pathways of the basal ganglia open or close movement gates, respectively. These repetitive behaviors may be ameliorated by drugs that augment D2 dopamine receptor responses or reduce D1 dopamine receptor responses. The article also notes the ubiquitous role of gating by basal ganglia loops in regulating all the functions that iSTART models. PMID:29593596

  19. The effect of low frequency stimulation of the pedunculopontine tegmental nucleus on basal ganglia in a rat model of Parkinson's disease.

    PubMed

    Park, Eunkyoung; Song, Inho; Jang, Dong Pyo; Kim, In Young

    2014-08-08

    The pedunculopontine nucleus (PPN) has recently been introduced as an alternative target to the subthalamic nucleus (STN) or globus pallidus internus (GPi) for the treatment of advanced Parkinson's disease with severe and medically intractable axial symptoms such as gait and postural impairment. However, it is little known about how electrical stimulation of the PPN affects control of neuronal activities between the PPN and basal ganglia. We examined how low frequency stimulation of the pedunculopontine tegmental nucleus (PPTg) affects control of neuronal activities between the PPN and basal ganglia in 6-OHDA lesioned rats. In order to identify the effect of low frequency stimulation on the PPTg, neuronal activity in both the STN and substantia nigra par reticulata (SNr) were recorded and subjected to quantitative analysis, including analysis of firing rates and firing patterns. In this study, we found that the firing rates of the STN and SNr were suppressed during low frequency stimulation of the PPTg. However, the firing pattern, in contrast to the firing rate, did not exhibit significant changes in either the STN or SNr of 6-OHDA lesioned rats during low frequency stimulation of the PPTg. In addition, we also found that the firing rate of STN and SNr neurons displaying burst and random pattern were decreased by low frequency stimulation of PPTg, while the neurons displaying regular pattern were not affected. These results indicate that low frequency stimulation of the PPTg affects neuronal activity in both the STN and SNr, and may represent electrophysiological efficacy of low frequency PPN stimulation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Emotional Speech Perception Unfolding in Time: The Role of the Basal Ganglia

    PubMed Central

    Paulmann, Silke; Ott, Derek V. M.; Kotz, Sonja A.

    2011-01-01

    The basal ganglia (BG) have repeatedly been linked to emotional speech processing in studies involving patients with neurodegenerative and structural changes of the BG. However, the majority of previous studies did not consider that (i) emotional speech processing entails multiple processing steps, and the possibility that (ii) the BG may engage in one rather than the other of these processing steps. In the present study we investigate three different stages of emotional speech processing (emotional salience detection, meaning-related processing, and identification) in the same patient group to verify whether lesions to the BG affect these stages in a qualitatively different manner. Specifically, we explore early implicit emotional speech processing (probe verification) in an ERP experiment followed by an explicit behavioral emotional recognition task. In both experiments, participants listened to emotional sentences expressing one of four emotions (anger, fear, disgust, happiness) or neutral sentences. In line with previous evidence patients and healthy controls show differentiation of emotional and neutral sentences in the P200 component (emotional salience detection) and a following negative-going brain wave (meaning-related processing). However, the behavioral recognition (identification stage) of emotional sentences was impaired in BG patients, but not in healthy controls. The current data provide further support that the BG are involved in late, explicit rather than early emotional speech processing stages. PMID:21437277

  1. Late onset familial dystonia: could mitochondrial deficits induce a diffuse lesioning process of the whole basal ganglia system?

    PubMed Central

    Caparros-Lefebvre, D; Destee, A; Petit, H

    1997-01-01

    BACKGROUND—Striatal necrosis has been related to various clinical syndromes, with acute or chronic progression, and juvenile or late occurrence, but the most common type is Leigh's encephalopathy.
METHODS—Between 1967 and 1995, six out of seven related patients with chronic familial dystonia were examined. MRIs were performed in four, between 1992-1994. The seven members, affected over three generations, were the father, three daughters (one surviving), and three surviving grandsons.
RESULTS—The leading symptoms were gait disorders and dystonia in all, dysarthria in six, verbal and motor stereotypies in two, and parkinsonian and cerebellar signs in three. Optic neuropathy was found in three. A frontal lobe syndrome without amnesia occurred in two. Symptoms occurred between the second and the fifth decade, with progressive deterioration. Magnetic resonance imaging, performed in four, showed in the two patients with severe neurological signs diffuse striatopallidal abnormal hyposignal (comparable with CSF signal) in T1 weighted images, suggesting extensive necrosis of the striatum and pallidum, associated with thalamo-subthalamo-rubro-dentato-nigral and substantia innominata hypersignals in T2 weighted images suggesting gliosis in these respective areas. The same images were described to a lesser extent in a third patient. Concentrations of lactate in CSF and serum were normal in three. Muscle biopsy, performed in four, was shown to be normal. Enzyme histochemistry showed complex I, III, and IV deficiency in surviving patients.
CONCLUSION—This familial dystonia of chronic progression may be related to basal ganglia necrosis or gliosis, associated with alterations in the respiratory chain. These metabolic alterations probably play a part in the pathophysiology of these unusual brain lesions.

 PMID:9285458

  2. Where neuroscience and dynamic system theory meet autonomous robotics: a contracting basal ganglia model for action selection.

    PubMed

    Girard, B; Tabareau, N; Pham, Q C; Berthoz, A; Slotine, J-J

    2008-05-01

    Action selection, the problem of choosing what to do next, is central to any autonomous agent architecture. We use here a multi-disciplinary approach at the convergence of neuroscience, dynamical system theory and autonomous robotics, in order to propose an efficient action selection mechanism based on a new model of the basal ganglia. We first describe new developments of contraction theory regarding locally projected dynamical systems. We exploit these results to design a stable computational model of the cortico-baso-thalamo-cortical loops. Based on recent anatomical data, we include usually neglected neural projections, which participate in performing accurate selection. Finally, the efficiency of this model as an autonomous robot action selection mechanism is assessed in a standard survival task. The model exhibits valuable dithering avoidance and energy-saving properties, when compared with a simple if-then-else decision rule.

  3. Believer-Skeptic Meets Actor-Critic: Rethinking the Role of Basal Ganglia Pathways during Decision-Making and Reinforcement Learning

    PubMed Central

    Dunovan, Kyle; Verstynen, Timothy

    2016-01-01

    The flexibility of behavioral control is a testament to the brain's capacity for dynamically resolving uncertainty during goal-directed actions. This ability to select actions and learn from immediate feedback is driven by the dynamics of basal ganglia (BG) pathways. A growing body of empirical evidence conflicts with the traditional view that these pathways act as independent levers for facilitating (i.e., direct pathway) or suppressing (i.e., indirect pathway) motor output, suggesting instead that they engage in a dynamic competition during action decisions that computationally captures action uncertainty. Here we discuss the utility of encoding action uncertainty as a dynamic competition between opposing control pathways and provide evidence that this simple mechanism may have powerful implications for bridging neurocomputational theories of decision making and reinforcement learning. PMID:27047328

  4. Evolution of the dynamic properties of the cortex-basal ganglia network after dopaminergic depletion in rats.

    PubMed

    Dejean, Cyril; Nadjar, Agnes; Le Moine, Catherine; Bioulac, Bernard; Gross, Christian E; Boraud, Thomas

    2012-05-01

    It is well established that parkinsonian syndrome is associated with alterations of neuronal activity temporal pattern basal ganglia (BG). An increase in synchronized oscillations has been observed in different BG nuclei in Parkinson's disease patients as well as animal models such as 6-hydroxydopamine treated rats. We recently demonstrated that this increase in oscillatory synchronization is present during high-voltage spindles (HVS) probably underpinned by the disorganization of cortex-BG interactions. Here we investigated the time course of both oscillatory and motor alterations. For that purpose we performed daily simultaneous recordings of neuronal activity in motor cortex, striatum and substantia nigra pars reticulata (SNr), before and after 6-hydroxydopamine lesion in awake rats. After a brief non-dopamine-specific desynchronization, oscillatory activity first increased during HVS followed by progressive motor impairment and the shortening of SNr activation delay. While the oscillatory firing increase reflects dopaminergic depletion, response alteration in SNr neurons is closely related to motor symptom. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Desynchronization of slow oscillations in the basal ganglia during natural sleep.

    PubMed

    Mizrahi-Kliger, Aviv D; Kaplan, Alexander; Israel, Zvi; Bergman, Hagai

    2018-05-01

    Slow oscillations of neuronal activity alternating between firing and silence are a hallmark of slow-wave sleep (SWS). These oscillations reflect the default activity present in all mammalian species, and are ubiquitous to anesthesia, brain slice preparations, and neuronal cultures. In all these cases, neuronal firing is highly synchronous within local circuits, suggesting that oscillation-synchronization coupling may be a governing principle of sleep physiology regardless of anatomical connectivity. To investigate whether this principle applies to overall brain organization, we recorded the activity of individual neurons from basal ganglia (BG) structures and the thalamocortical (TC) network over 70 full nights of natural sleep in two vervet monkeys. During SWS, BG neurons manifested slow oscillations (∼0.5 Hz) in firing rate that were as prominent as in the TC network. However, in sharp contrast to any neural substrate explored thus far, the slow oscillations in all BG structures were completely desynchronized between individual neurons. Furthermore, whereas in the TC network single-cell spiking was locked to slow oscillations in the local field potential (LFP), the BG LFP exhibited only weak slow oscillatory activity and failed to entrain nearby cells. We thus show that synchrony is not inherent to slow oscillations, and propose that the BG desynchronization of slow oscillations could stem from its unique anatomy and functional connectivity. Finally, we posit that BG slow-oscillation desynchronization may further the reemergence of slow-oscillation traveling waves from multiple independent origins in the frontal cortex, thus significantly contributing to normal SWS.

  6. Fiber tractography of the axonal pathways linking the basal ganglia and cerebellum in Parkinson disease: implications for targeting in deep brain stimulation.

    PubMed

    Sweet, Jennifer A; Walter, Benjamin L; Gunalan, Kabilar; Chaturvedi, Ashutosh; McIntyre, Cameron C; Miller, Jonathan P

    2014-04-01

    Stimulation of white matter pathways near targeted structures may contribute to therapeutic effects of deep brain stimulation (DBS) for patients with Parkinson disease (PD). Two tracts linking the basal ganglia and cerebellum have been described in primates: the subthalamopontocerebellar tract (SPCT) and the dentatothalamic tract (DTT). The authors used fiber tractography to evaluate white matter tracts that connect the cerebellum to the region of the basal ganglia in patients with PD who were candidates for DBS. Fourteen patients with advanced PD underwent 3-T MRI, including 30-directional diffusion-weighted imaging sequences. Diffusion tensor tractography was performed using 2 regions of interest: ipsilateral subthalamic and red nuclei, and contralateral cerebellar hemisphere. Nine patients underwent subthalamic DBS, and the course of each tract was observed relative to the location of the most effective stimulation contact and the volume of tissue activated. In all patients 2 distinct tracts were identified that corresponded closely to the described anatomical features of the SPCT and DTT, respectively. The mean overall distance from the active contact to the DTT was 2.18 ± 0.35 mm, and the mean proportional distance relative to the volume of tissue activated was 1.35 ± 0.48. There was a nonsignificant trend toward better postoperative tremor control in patients with electrodes closer to the DTT. The SPCT and the DTT may be related to the expression of symptoms in PD, and this may have implications for DBS targeting. The use of tractography to identify the DTT might assist with DBS targeting in the future.

  7. Inorganic phosphorus (Pi) in CSF is a biomarker for SLC20A2-associated idiopathic basal ganglia calcification (IBGC1).

    PubMed

    Hozumi, Isao; Kurita, Hisaka; Ozawa, Kazuhiro; Furuta, Nobuyuki; Inden, Masatoshi; Sekine, Shin-Ichiro; Yamada, Megumi; Hayashi, Yuichi; Kimura, Akio; Inuzuka, Takashi; Seishima, Mitsuru

    2018-05-15

    Idiopathic basal ganglia calcification (IBGC), also called Fahr's disease or recently primary familial brain calcification (PFBC), is characterized by abnormal deposits of minerals including calcium mainly and phosphate in the brain. Mutations in SLC20A2 (IBGC1 (merged with former IBGC2 and IBGC3)), which encodes PiT-2, a phosphate transporter, is the major cause of IBGC. Recently, Slc20a2-KO mice have been showed to have elevated levels of inorganic phosphorus (Pi) in cerebrospinal fluid (CSF); however, CSF Pi levels in patients with IBGC have not been fully examined. We investigated the cases of 29 patients with IBGC including six patients with SLC20A2 mutation and three patients with PDGFB mutation, and 13 controls. The levels of sodium (Na), potassium (K), chloride (Cl), calcium (Ca), and Pi in sera and CSF were determined by potentiometry and colorimetry. Moreover, clinical manifestations were investigated in the IBGC patients with high Pi levels in CSF. The study revealed that the average level of Pi in the CSF of the total group of patients with IBGC is significantly higher than that of the control group, and the levels of Pi in CSF of the IBGC patients with SLC20A2 mutations are significantly higher than those of the IBGC patients with PDGFB mutations, the other IBGC patients and controls. Results of this study suggest that the levels of CSF Pi will be a good biomarker for IBGC1. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Electro-acupuncture stimulation acts on the basal ganglia output pathway to ameliorate motor impairment in Parkinsonian model rats.

    PubMed

    Jia, Jun; Li, Bo; Sun, Zuo-Li; Yu, Fen; Wang, Xuan; Wang, Xiao-Min

    2010-04-01

    The role of electro-acupuncture (EA) stimulation on motor symptoms in Parkinson's disease (PD) has not been well studied. In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), EA stimulation improved motor impairment in a frequency-dependent manner. Whereas EA stimulation at a low frequency (2 Hz) had no effect, EA stimulation at a high frequency (100 Hz) significantly improved motor coordination. However, neither low nor high EA stimulation could significantly enhance dopamine levels in the striatum. EA stimulation at 100 Hz normalized the MFB lesion-induced increase in midbrain GABA content, but it had no effect on GABA content in the globus pallidus. These results suggest that high-frequency EA stimulation improves motor impairment in MFB-lesioned rats by increasing GABAergic inhibition in the output structure of the basal ganglia.

  9. Motor Control Abnormalities in Parkinson’s Disease

    PubMed Central

    Mazzoni, Pietro; Shabbott, Britne; Cortés, Juan Camilo

    2012-01-01

    The primary manifestations of Parkinson’s disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms. Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb’s position and speed, are controlled and coordinated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson’s disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neural prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of understanding, however, remains limited, partly because of limitations in our knowledge of normal motor control. In this article, we review the concept of motor control and describe a few motor symptoms that illustrate the challenges in understanding such symptoms as motor control abnormalities. PMID:22675667

  10. Sensory aspects of movement disorders

    PubMed Central

    Patel, Neepa; Jankovic, Joseph; Hallett, Mark

    2016-01-01

    Movement disorders, which include disorders such as Parkinson’s disease, dystonia, Tourette’s syndrome, restless legs syndrome, and akathisia, have traditionally been considered to be disorders of impaired motor control resulting predominantly from dysfunction of the basal ganglia. This notion has been revised largely because of increasing recognition of associated behavioural, psychiatric, autonomic, and other non-motor symptoms. The sensory aspects of movement disorders include intrinsic sensory abnormalities and the effects of external sensory input on the underlying motor abnormality. The basal ganglia, cerebellum, thalamus, and their connections, coupled with altered sensory input, seem to play a key part in abnormal sensorimotor integration. However, more investigation into the phenomenology and physiological basis of sensory abnormalities, and about the role of the basal ganglia, cerebellum, and related structures in somatosensory processing, and its effect on motor control, is needed. PMID:24331796

  11. Real-time simulation of a spiking neural network model of the basal ganglia circuitry using general purpose computing on graphics processing units.

    PubMed

    Igarashi, Jun; Shouno, Osamu; Fukai, Tomoki; Tsujino, Hiroshi

    2011-11-01

    Real-time simulation of a biologically realistic spiking neural network is necessary for evaluation of its capacity to interact with real environments. However, the real-time simulation of such a neural network is difficult due to its high computational costs that arise from two factors: (1) vast network size and (2) the complicated dynamics of biologically realistic neurons. In order to address these problems, mainly the latter, we chose to use general purpose computing on graphics processing units (GPGPUs) for simulation of such a neural network, taking advantage of the powerful computational capability of a graphics processing unit (GPU). As a target for real-time simulation, we used a model of the basal ganglia that has been developed according to electrophysiological and anatomical knowledge. The model consists of heterogeneous populations of 370 spiking model neurons, including computationally heavy conductance-based models, connected by 11,002 synapses. Simulation of the model has not yet been performed in real-time using a general computing server. By parallelization of the model on the NVIDIA Geforce GTX 280 GPU in data-parallel and task-parallel fashion, faster-than-real-time simulation was robustly realized with only one-third of the GPU's total computational resources. Furthermore, we used the GPU's full computational resources to perform faster-than-real-time simulation of three instances of the basal ganglia model; these instances consisted of 1100 neurons and 33,006 synapses and were synchronized at each calculation step. Finally, we developed software for simultaneous visualization of faster-than-real-time simulation output. These results suggest the potential power of GPGPU techniques in real-time simulation of realistic neural networks. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Knockdown of sodium channel NaV1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia

    PubMed Central

    Xie, Wenrui; Strong, Judith A.; Ye, Ling; Mao, Ju-Xian; Zhang, Jun-Ming

    2013-01-01

    Inflammatory processes in the sensory ganglia contribute to many forms of chronic pain. We previously showed that local inflammation of the lumbar sensory ganglia rapidly leads to prolonged mechanical pain behaviors and high levels of spontaneous bursting activity in myelinated cells. Abnormal spontaneous activity of sensory neurons occurs early in many preclinical pain models, and initiates many other pathological changes, but its molecular basis is not well understood. The sodium channel isoform NaV1.6 can underlie repetitive firing and excitatory persistent and resurgent currents. We used in vivo knockdown of this channel via local injection of siRNA to examine its role in chronic pain following local inflammation of the rat lumbar sensory ganglia. In normal DRG, quantitative PCR showed that cells capable of firing repetitively had significantly higher relative expression of NaV1.6. In inflamed DRG, spontaneously active bursting cells expressed high levels of NaV1.6′ immunoreactivity. In vivo knockdown of NaV1.6 locally in the lumbar DRG at the time of DRG inflammation completely blocked development of pain behaviors and abnormal spontaneous activity, while having only minor effects on unmyelinated C-cells. Current research on isoform-specific sodium channel blockers for chronic pain is largely focused on NaV1.8, because it is present primarily in unmyelinated C fiber nociceptors, or on NaV1.7, because lack of this channel causes congenital indifference to pain. However, the results suggest that NaV1.6 may be a useful therapeutic target for chronic pain, and that some pain conditions may be primarily mediated by myelinated A-fiber sensory neurons. PMID:23622763

  13. Decision making under uncertainty in a spiking neural network model of the basal ganglia.

    PubMed

    Héricé, Charlotte; Khalil, Radwa; Moftah, Marie; Boraud, Thomas; Guthrie, Martin; Garenne, André

    2016-12-01

    The mechanisms of decision-making and action selection are generally thought to be under the control of parallel cortico-subcortical loops connecting back to distinct areas of cortex through the basal ganglia and processing motor, cognitive and limbic modalities of decision-making. We have used these properties to develop and extend a connectionist model at a spiking neuron level based on a previous rate model approach. This model is demonstrated on decision-making tasks that have been studied in primates and the electrophysiology interpreted to show that the decision is made in two steps. To model this, we have used two parallel loops, each of which performs decision-making based on interactions between positive and negative feedback pathways. This model is able to perform two-level decision-making as in primates. We show here that, before learning, synaptic noise is sufficient to drive the decision-making process and that, after learning, the decision is based on the choice that has proven most likely to be rewarded. The model is then submitted to lesion tests, reversal learning and extinction protocols. We show that, under these conditions, it behaves in a consistent manner and provides predictions in accordance with observed experimental data.

  14. Executive dysfunction, obsessive-compulsive symptoms, and attention deficit and hyperactivity disorder in Systemic Lupus Erythematosus: Evidence for basal ganglia dysfunction?

    PubMed

    Maciel, Ricardo Oliveira Horta; Ferreira, Gilda Aparecida; Akemy, Bárbara; Cardoso, Francisco

    2016-01-15

    Chorea is well described in a group of patients with Systemic Lupus Erythematosus (SLE). There is less information, however, on other movement disorders as well as non-motor neuropsychiatric features such as obsessive-compulsive symptoms (OCS), executive dysfunction and attention deficit and hyperactivity disorder (ADHD) in subjects with SLE. Fifty-four subjects with SLE underwent a battery of neuropsychiatric tests that included the Mini Mental State Examination, the Montreal Cognitive Assessment, the Frontal Assessment Battery (FAB), the FAS verbal and the categorical (animals) semantic fluency tests, the Obsessive and Compulsive Inventory - Revised, the Yale-Brown Obsessive and Compulsive Scale and Beck's Anxiety and Depression Scales. ADHD was diagnosed according to DSM-IV criteria. SLE disease activity and cumulative damage were evaluated according to the modified SLE Disease Activity Index 2000 (mSLEDAI-2K) and the SLICC/ACR, respectively. Six (11.1%) and 33 (61.1%) patients had cognitive impairment according to the MMSE and MoCA, respectively. Eleven (20.4%) had abnormal FAB scores, and 5 (9.3%) had lower semantic fluency scores than expected. The overall frequency of cognitive dysfunction was 72.2% (39 patients) and of neuropsychiatric SLE was 77.8% (42 patients). Two patients (3.7%) had movement disorders. Fifteen (27.8%) had OCS and 17 (31.5%) met diagnostic criteria for ADHD. ADHD and OCS correlated with higher disease activity, p=0.003 and 0.006, respectively. Higher cumulative damage correlated with lower FAB scores (p 0.026). Executive dysfunction, ADHD, OCS, and movement disorders are common in SLE. Our finding suggests that there is frequent basal ganglia dysfunction in SLE. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Effect of exposure to polycyclic aromatic hydrocarbons on basal ganglia and attention-deficit hyperactivity disorder symptoms in primary school children.

    PubMed

    Mortamais, Marion; Pujol, Jesus; van Drooge, Barend L; Macià, Didac; Martínez-Vilavella, Gerard; Reynes, Christelle; Sabatier, Robert; Rivas, Ioar; Grimalt, Joan; Forns, Joan; Alvarez-Pedrerol, Mar; Querol, Xavier; Sunyer, Jordi

    2017-08-01

    Polycyclic aromatic hydrocarbons (PAHs) have been proposed as environmental risk factors for attention deficit hyperactivity disorder (ADHD). The effects of these pollutants on brain structures potentially involved in the pathophysiology of ADHD are unknown. The aim of this study was to investigate the effects of PAHs on basal ganglia volumes and ADHD symptoms in school children. We conducted an imaging study in 242 children aged 8-12years, recruited through a set of representative schools of the city of Barcelona, Spain. Indoor and outdoor PAHs and benzo[a]pyrene (BPA) levels were assessed in the school environment, one year before the MRI assessment. Whole-brain volumes and basal ganglia volumes (caudate nucleus, globus pallidus, putamen) were derived from structural MRI scans using automated tissue segmentation. ADHD symptoms (ADHD/DSM-IV Scales, American Psychiatric Association 2002) were reported by teachers, and inattentiveness was evaluated with standard error of hit reaction time in the attention network computer-based test. Total PAHs and BPA were associated with caudate nucleus volume (CNV) (i.e., an interquartile range increase in BPA outdoor level (67pg/m 3 ) and indoor level (76pg/m 3 ) was significantly linked to a decrease in CNV (mm 3 ) (β=-150.6, 95% CI [-259.1, -42.1], p=0.007, and β=-122.4, 95% CI [-232.9, -11.8], p=0.030 respectively) independently of intracranial volume, age, sex, maternal education and socioeconomic vulnerability index at home). ADHD symptoms and inattentiveness increased in children with higher exposure to BPA, but these associations were not statistically significant. Exposure to PAHs, and in particular to BPA, is associated with subclinical changes on the caudate nucleus, even below the legislated annual target levels established in the European Union. The behavioral consequences of this induced brain change were not identified in this study, but given the caudate nucleus involvement in many crucial cognitive and behavior

  16. Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans

    PubMed Central

    Haagensen, Brian N.; Christensen, Mark S.; Madsen, Kristoffer H.; Rowe, James B.; Løkkegaard, Annemette; Siebner, Hartwig R.

    2015-01-01

    Dopaminergic signalling in the striatum contributes to reinforcement of actions and motivational enhancement of motor vigour. Parkinson's disease leads to progressive dopaminergic denervation of the striatum, impairing the function of cortico-basal ganglia networks. While levodopa therapy alleviates basal ganglia dysfunction in Parkinson's disease, it often elicits involuntary movements, referred to as levodopa-induced peak-of-dose dyskinesias. Here, we used a novel pharmacodynamic neuroimaging approach to identify the changes in cortico-basal ganglia connectivity that herald the emergence of levodopa-induced dyskinesias. Twenty-six patients with Parkinson's disease (age range: 51–84 years; 11 females) received a single dose of levodopa and then performed a task in which they had to produce or suppress a movement in response to visual cues. Task-related activity was continuously mapped with functional magnetic resonance imaging. Dynamic causal modelling was applied to assess levodopa-induced modulation of effective connectivity between the pre-supplementary motor area, primary motor cortex and putamen when patients suppressed a motor response. Bayesian model selection revealed that patients who later developed levodopa-induced dyskinesias, but not patients without dyskinesias, showed a linear increase in connectivity between the putamen and primary motor cortex after levodopa intake during movement suppression. Individual dyskinesia severity was predicted by levodopa-induced modulation of striato-cortical feedback connections from putamen to the pre-supplementary motor area (Pcorrected = 0.020) and primary motor cortex (Pcorrected = 0.044), but not feed-forward connections from the cortex to the putamen. Our results identify for the first time, aberrant dopaminergic modulation of striatal-cortical connectivity as a neural signature of levodopa-induced dyskinesias in humans. We argue that excessive striato-cortical connectivity in response to levodopa produces an

  17. Inhibitory Control in the Cortico-Basal Ganglia-Thalamocortical Loop: Complex Regulation and Interplay with Memory and Decision Processes.

    PubMed

    Wei, Wei; Wang, Xiao-Jing

    2016-12-07

    We developed a circuit model of spiking neurons that includes multiple pathways in the basal ganglia (BG) and is endowed with feedback mechanisms at three levels: cortical microcircuit, corticothalamic loop, and cortico-BG-thalamocortical system. We focused on executive control in a stop signal task, which is known to depend on BG across species. The model reproduces a range of experimental observations and shows that the newly discovered feedback projection from external globus pallidus to striatum is crucial for inhibitory control. Moreover, stopping process is enhanced by the cortico-subcortical reverberatory dynamics underlying persistent activity, establishing interdependence between working memory and inhibitory control. Surprisingly, the stop signal reaction time (SSRT) can be adjusted by weights of certain connections but is insensitive to other connections in this complex circuit, suggesting novel circuit-based intervention for inhibitory control deficits associated with mental illness. Our model provides a unified framework for inhibitory control, decision making, and working memory. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Larger Gray Matter Volume in the Basal Ganglia of Heavy Cannabis Users Detected by Voxel-Based Morphometry and Subcortical Volumetric Analysis.

    PubMed

    Moreno-Alcázar, Ana; Gonzalvo, Begoña; Canales-Rodríguez, Erick J; Blanco, Laura; Bachiller, Diana; Romaguera, Anna; Monté-Rubio, Gemma C; Roncero, Carlos; McKenna, Peter J; Pomarol-Clotet, Edith

    2018-01-01

    Background: Structural imaging studies of cannabis users have found evidence of both cortical and subcortical volume reductions, especially in cannabinoid receptor-rich regions such as the hippocampus and amygdala. However, the findings have not been consistent. In the present study, we examined a sample of adult heavy cannabis users without other substance abuse to determine whether long-term use is associated with brain structural changes, especially in the subcortical regions. Method: We compared the gray matter volume of 14 long-term, heavy cannabis users with non-using controls. To provide robust findings, we conducted two separate studies using two different MRI techniques. Each study used the same sample of cannabis users and a different control group, respectively. Both control groups were independent of each other. First, whole-brain voxel-based morphometry (VBM) was used to compare the cannabis users against 28 matched controls (HC1 group). Second, a volumetric analysis of subcortical regions was performed to assess differences between the cannabis users and a sample of 100 matched controls (HC2 group) obtained from a local database of healthy volunteers. Results: The VBM study revealed that, compared to the control group HC1, the cannabis users did not show cortical differences nor smaller volume in any subcortical structure but showed a cluster ( p < 0.001) of larger GM volume in the basal ganglia, involving the caudate, putamen, pallidum, and nucleus accumbens, bilaterally. The subcortical volumetric analysis revealed that, compared to the control group HC2, the cannabis users showed significantly larger volumes in the putamen ( p = 0.001) and pallidum ( p = 0.0015). Subtle trends, only significant at the uncorrected level, were also found in the caudate ( p = 0.05) and nucleus accumbens ( p = 0.047). Conclusions: This study does not support previous findings of hippocampal and/or amygdala structural changes in long-term, heavy cannabis users. It does

  19. Proceedings of the workshop on Cerebellum, Basal Ganglia and Cortical Connections Unmasked in Health and Disorder held in Brno, Czech Republic, October 17th, 2013.

    PubMed

    Bareš, Martin; Apps, Richard; Kikinis, Zora; Timmann, Dagmar; Oz, Gulin; Ashe, James J; Loft, Michaela; Koutsikou, Stella; Cerminara, Nadia; Bushara, Khalaf O; Kašpárek, Tomáš

    2015-04-01

    The proceedings of the workshop synthesize the experimental, preclinical, and clinical data suggesting that the cerebellum, basal ganglia (BG), and their connections play an important role in pathophysiology of various movement disorders (like Parkinson's disease and atypical parkinsonian syndromes) or neurodevelopmental disorders (like autism). The contributions from individual distinguished speakers cover the neuroanatomical research of complex networks, neuroimaging data showing that the cerebellum and BG are connected to a wide range of other central nervous system structures involved in movement control. Especially, the cerebellum plays a more complex role in how the brain functions than previously thought.

  20. Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia.

    PubMed

    Simonyan, Kristina; Berman, Brian D; Herscovitch, Peter; Hallett, Mark

    2013-09-11

    Spasmodic dysphonia is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. The pathophysiology of spasmodic dysphonia is thought to involve structural and functional abnormalities in the basal ganglia-thalamo-cortical circuitry; however, neurochemical correlates underpinning these abnormalities as well as their relations to spasmodic dysphonia symptoms remain unknown. We used positron emission tomography with the radioligand [(11)C]raclopride (RAC) to study striatal dopaminergic neurotransmission at the resting state and during production of symptomatic sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We found that patients, compared to healthy controls, had bilaterally decreased RAC binding potential (BP) to striatal dopamine D2/D3 receptors on average by 29.2%, which was associated with decreased RAC displacement (RAC ΔBP) in the left striatum during symptomatic speaking (group average difference 10.2%), but increased RAC ΔBP in the bilateral striatum during asymptomatic tapping (group average difference 10.1%). Patients with more severe voice symptoms and subclinically longer reaction time to initiate the tapping sequence had greater RAC ΔBP measures, while longer duration of spasmodic dysphonia was associated with a decrease in task-induced RAC ΔBP. Decreased dopaminergic transmission during symptomatic speech production may represent a disorder-specific pathophysiological trait involved in symptom generation, whereas increased dopaminergic function during unaffected task performance may be explained by a compensatory adaptation of the nigrostriatal dopaminergic system possibly due to decreased striatal D2/D3 receptor availability. These changes can be linked to the clinical and subclinical features of spasmodic dysphonia and may represent the neurochemical basis of basal ganglia alterations in this disorder.

  1. Dimensions of subcortical infarcts associated with first- to third-order branches of the basal ganglia arteries.

    PubMed

    Phan, Thanh G; van der Voort, Sanne; Beare, Richard; Ma, Henry; Clissold, Benjamin; Holt, Michael; Ly, John; Foster, Emma; Thong, Eleanor; Stuckey, Stephen; Cassell, Martin D; Srikanth, Velandai

    2013-01-01

    It has been described that lacunar infarct is characterized by its smallish size (15-20 mm) in the axial plane. However, the size of the basal ganglia artery responsible for this type of infarct is uncertain. Detection of small arterial occlusion is not possible with current angiography, hindering correlation of arterial occlusion with subcortical infarct size. Recently, investigators have published microangiographic templates of arteries supplying the basal ganglia. These templates display first-order (proximal) to third-order (distal) branching of these arteries and can help with estimating the likely site of arterial disease in subcortical infarcts. We correlated the dimensions of subcortical infarcts with the order of arterial branching described in a microangiographic template. Such data may provide further clues about the type of arteries associated with subcortical infarcts and assist in refining the concept of lacunar infarction. Patients with subcortical infarcts on MR imaging (MRI) admitted to our institution between 2009 and 2011 were included in the study. Infarcts were manually segmented and registered to a standard brain template. These segmented infarcts were scaled and overlapped with published microangiographic templates, and used by 6 raters who independently estimated the branching order of arterial disease that might result in these infarcts. We used regression analysis to relate these ratings to infarct dimensions. Among 777 patients, there were 33 (58% male) patients with subcortical infarcts. The mean age was 63.1 ± 15.1 years. Infarct dimensions for the groups were as follows: group 1 (first-order branch): height 37.6 ± 7.4 mm, horizontal width 21.2 ± 11.6 mm, anterior-posterior length 36.8 ± 20.1 mm; group 2 (second-order branch): height 25.2 ± 7.9 mm, horizontal width 16.6 ± 22.8 mm, anterior-posterior length 16.1 ± 8.0 mm; group 3 (third-order branch): height 11.6 ± 5.7 mm, axial width 5.3 ± 3.1 mm, anterior-posterior length 5

  2. Limbic and Basal Ganglia Neuroanatomical Correlates of Gait and Executive Function: Older Adults With Mild Cognitive Impairment and Intact Cognition.

    PubMed

    McGough, Ellen L; Kelly, Valerie E; Weaver, Kurt E; Logsdon, Rebecca G; McCurry, Susan M; Pike, Kenneth C; Grabowski, Thomas J; Teri, Linda

    2018-04-01

    This study aimed to examine differences in spatiotemporal gait parameters between older adults with amnestic mild cognitive impairment and normal cognition and to examine limbic and basal ganglia neural correlates of gait and executive function in older adults without dementia. This was a cross-sectional study of 46 community-dwelling older adults, ages 70-95 yrs, with amnestic mild cognitive impairment (n = 23) and normal cognition (n = 23). Structural magnetic resonance imaging was used to attain volumetric measures of limbic and basal ganglia structures. Quantitative motion analysis was used to measure spatiotemporal parameters of gait. The Trail Making Test was used to assess executive function. During fast-paced walking, older adults with amnestic mild cognitive impairment demonstrated significantly slower gait speed and shorter stride length compared with older adults with normal cognition. Stride length was positively correlated with hippocampal, anterior cingulate, and nucleus accumbens volumes (P < 0.05). Executive function was positively correlated with hippocampal, anterior cingulate, and posterior cingulate volumes (P < 0.05). Compared with older adults with normal cognition, those with amnestic mild cognitive impairment demonstrated slower gait speed and shorter stride length, during fast-paced walking, and lower executive function. Hippocampal and anterior cingulate volumes demonstrated moderate positive correlation with both gait and executive function, after adjusting for age. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) discuss gait performance and cognitive function in older adults with amnestic mild cognitive impairment versus normal cognition, (2) discuss neurocorrelates of gait and executive function in older adults without dementia, and (3) recognize the importance of assessing gait speed and cognitive

  3. rTMS with Motor Training Modulates Cortico-Basal Ganglia-Thalamocortical Circuits in Stroke Patients

    PubMed Central

    Chang, Won Hyuk; Kim, Yun-Hee; Yoo, Woo-Kyoung; Goo, Kyoung-Hyup; Park, Chang-hyun; Kim, Sung Tae; Pascual-Leone, Alvaro

    2013-01-01

    Background and Purpose Repetitive transcranial magnetic stimulation (rTMS) may enhance plastic changes in the human cortex and modulation of behavior. However, the underlying neural mechanisms have not been sufficiently investigated. We examined the clinical effects and neural correlates of high-frequency rTMS coupled with motor training in patients with hemiparesis after stroke. Methods Twenty-one patients were randomly divided into two groups, and received either real or sham rTMS. Ten daily sessions of 1,000 pulses of real or sham rTMS were applied at 10 Hz over the primary motor cortex of the affected hemisphere, coupled with sequential finger motor training of the paretic hand. Functional MRIs were obtained before and after training using sequential finger motor tasks, and performances were assessed. Results Following rTMS intervention, movement accuracy of sequential finger motor tasks showed significantly greater improvement in the real group than in the sham group (p<0.05). Real rTMS modulated areas of brain activation during performance of motor tasks with a significant interaction effect in the sensorimotor cortex, thalamus, and caudate nucleus. Patients in the real rTMS group also showed significantly enhanced activation in the affected hemisphere compared to the sham rTMS group. Conclusion According to these results, a 10 day course of high-frequency rTMS coupled with motor training improved motor performance through modulation of activities in the cortico-basal ganglia-thalamocortical circuits. PMID:22555430

  4. Distribution and properties of GABA(B) antagonist [3H]CGP 62349 binding in the rhesus monkey thalamus and basal ganglia and the influence of lesions in the reticular thalamic nucleus.

    PubMed

    Ambardekar, A V; Ilinsky, I A; Forestl, W; Bowery, N G; Kultas-Ilinsky, K

    1999-01-01

    GABA(B) receptors are believed to be associated with the efferents of the nucleus reticularis thalami, which is implicated in the regulation of activity in the thalamocortical-corticothalamic circuit and plays a role in absence seizures. Yet, the distribution of GABA(B) receptors in the thalamus has only been studied in the rat, and there is no comparable information in primates. The potent GABA(B) receptor antagonist [3H]CGP 62349 was used to study the distribution and binding properties of the receptor in control monkeys and those with small ibotenic acid lesions in the anterodorsal segment of the nucleus reticularis thalami. Eight-micrometer-thick cryostat sections of the fresh frozen brains were incubated in the presence of varying concentrations of the ligand. Autoradiographs were analysed using a quantitative image analysis technique, and binding parameters were calculated for select thalamic nuclei as well as basal ganglia structures present in the same sections. The overall number of GABA(B) binding sites in the monkey thalamus and basal ganglia was several-fold higher than previously reported values for the rat. In the thalamus, the receptors were distributed rather uniformly and the binding densities and affinities were high (Bmax range of 245.5-437.9 fmol/ mg of tissue, Kd range of 0.136-0.604 nM). In the basal ganglia, the number of binding sites and the affinities were lower (Bmax range of 51.1-244.2 fmol/mg of tissue; K(d) range of 0.416-1.394 nM), and the differences between nuclei were more pronounced, with striatum and substantia nigra pars compacta displaying the highest binding densities. Seven days post-lesion, a 20-30% decrease in Bmax values (P < 0.05) was found in the nuclei receiving input from the lesioned nucleus reticularis thalami sector (the mediodorsal nucleus and densicellular and magnocellular parts of the ventral anterior nucleus) without changes in affinity. No significant changes were detected in any other structures. The results

  5. Parallel and interactive learning processes within the basal ganglia: relevance for the understanding of addiction.

    PubMed

    Belin, David; Jonkman, Sietse; Dickinson, Anthony; Robbins, Trevor W; Everitt, Barry J

    2009-04-12

    In this review we discuss the evidence that drug addiction, defined as a maladaptive compulsive habit, results from the progressive subversion by addictive drugs of striatum-dependent operant and Pavlovian learning mechanisms that are usually involved in the control over behaviour by stimuli associated with natural reinforcement. Although mainly organized through segregated parallel cortico-striato-pallido-thalamo-cortical loops involved in motor or emotional functions, the basal ganglia, and especially the striatum, are key mediators of the modulation of behavioural responses, under the control of both action-outcome and stimulus-response mechanisms, by incentive motivational processes and Pavlovian associations. Here we suggest that protracted exposure to addictive drugs recruits serial and dopamine-dependent, striato-nigro-striatal ascending spirals from the nucleus accumbens to more dorsal regions of the striatum that underlie a shift from action-outcome to stimulus-response mechanisms in the control over drug seeking. When this progressive ventral to dorsal striatum shift is combined with drug-associated Pavlovian influences from limbic structures such as the amygdala and the orbitofrontal cortex, drug seeking behaviour becomes established as an incentive habit. This instantiation of implicit sub-cortical processing of drug-associated stimuli and instrumental responding might be a key mechanism underlying the development of compulsive drug seeking and the high vulnerability to relapse which are hallmarks of drug addiction.

  6. Proton magnetic resonance spectroscopy of late-life major depressive disorder.

    PubMed

    Chen, Cheng-Sheng; Chiang, I-Chan; Li, Chun-Wei; Lin, Wei-Chen; Lu, Chia-Ying; Hsieh, Tsyh-Jyi; Liu, Gin-Chung; Lin, Hsiu-Fen; Kuo, Yu-Ting

    2009-06-30

    The primary goal of this study was to examine the biochemical abnormalities of late-life major depression by using 3-tesla (3-T) proton magnetic resonance spectroscopy ((1)H-MRS). The antidepressant effects on the biochemical abnormalities were investigated as well. Study participants were 27 elderly patients with major depressive disorders (among which 9 were on antidepressant medication) and 19 comparison elderly subjects. (1)H-MRS spectra were acquired from voxels that were placed in the left frontal white matter, left periventricular white matter, and left basal ganglia. Ratios of N-acetylaspartate (NAA), choline (Cho) and myo-inositol to creatine were calculated. Patients with late-life major depressive disorder had a significantly lower NAA/creatine ratio in the left frontal white matter, and higher Cho/creatine and myo-inositol/creatine ratios in the left basal ganglia when compared with the control subjects. The myo-inositol correlated with global cognitive function among the patients. The biochemical abnormalities in late-life major depressive disorder were found on the left side of the frontal white matter and the basal ganglia. Neuron degeneration in the frontal white matter and second messenger system dysfunction or glial dysfunction in the basal ganglia are suggested to be associated with late-life depression.

  7. Perspective on basal ganglia connections as described by Nauta and Mehler in 1966: Where we were and how this paper effected where we are now.

    PubMed

    Haber, Suzanne

    2016-08-15

    identified. Most, and possibly all, of the ansal fibers composing the so-called pallidohypothalamic tract loop back into Forel's fields after a shorter or longer descent into the hypothalamus. (d) Fibers of the fasciculus lenticularis by-passing the thalamus are distributed to the nucleus of Forel's field H (prerubral field). Longer fibers of the same category pass caudalward lateral and ventral to the red nucleus and terminate in the nucleus tegmenti pedunculopontinus, particularly in the latter's caudal subnucleus compactus (terminology of Olszewski and Baxter). A few such pallidomesencephalic fibers appear to end in a small circumscript caudal area of the substantia nigra, pars compacta. No evidence was obtained of pallidotegmental fibers extending caudally beyond the mesencephalon. (e) Pallidal efferents to the zona incerta could not be identified. Only sporadic pallidofugal fibers could be followed to the red nucleus, nucleus interstitialis, and nucleus of Darkschewitsch. The article, 'Projections of the lentiform nucleus in the monkey', by Walle J.H. Nauta and William R. Mehler used a relatively new anatomical tracing method that allowed visualization of degenerating myelin following carefully placed lesions to identify the efferent projections from the lentiform nucleus. While several of the basal ganglia pathways had been described or suspected, this publication validated many of these, resolved controversies regarding some connections, and demonstrated a few that had not previously been shown. This seminal paper became a main reference for basal ganglia connections until newer, more specific tracer techniques were developed. Several students and colleagues who worked closely with Nauta continued to use anatomical tracing methods to make key important contributions to delineating basal ganglia circuits and function. Collectively these studies have impacted greatly on our understanding of the role of the basal ganglia in normal behavior and in neurological and

  8. Dopamine physiology in the basal ganglia of male zebra finches during social stimulation.

    PubMed

    Ihle, Eva C; van der Hart, Marieke; Jongsma, Minke; Tecott, Larry H; Doupe, Allison J

    2015-06-01

    Accumulating evidence suggests that dopamine (DA) is involved in altering neural activity and gene expression in a zebra finch cortical-basal ganglia circuit specialized for singing, upon the shift between solitary singing and singing as a part of courtship. Our objective here was to sample changes in the extracellular concentrations of DA in Area X of adult and juvenile birds, to test the hypothesis that DA levels would change similarly during presentation of a socially salient stimulus in both age groups. We used microdialysis to sample the extracellular milieu of Area X in awake, behaving adult and juvenile male zebra finches, and analysed the dialysate using high-performance liquid chromatography coupled with electrochemical detection. The extracellular levels of DA in Area X increased significantly during both female presentation to adult males and tutor presentation to juvenile males. DA levels were not correlated with the time spent singing. We also reverse-dialysed Area X with pharmacologic agents that act either on DA systems directly or on norepinephrine, and found that all of these agents significantly increased DA levels (3- to 10-fold) in Area X. These findings suggest that changes in extracellular DA levels can be stimulated similarly by very different social contexts (courtship and interaction with tutor), and influenced potently by dopaminergic and noradrenergic drugs. These results raise the possibility that the arousal level or attentional state of the subject (rather than singing behavior) is the common feature eliciting changes in extracellular DA concentration. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  9. Voluntary saccade inhibition deficits correlate with extended white-matter cortico-basal atrophy in Huntington's disease.

    PubMed

    Vaca-Palomares, Israel; Coe, Brian C; Brien, Donald C; Munoz, Douglas P; Fernandez-Ruiz, Juan

    2017-01-01

    The ability to inhibit automatic versus voluntary saccade commands in demanding situations can be impaired in neurodegenerative diseases such as Huntington's disease (HD). These deficits could result from disruptions in the interaction between basal ganglia and the saccade control system. To investigate voluntary oculomotor control deficits related to the cortico-basal circuitry, we evaluated early HD patients using an interleaved pro- and anti-saccade task that requires flexible executive control to generate either an automatic response (look at a peripheral visual stimulus) or a voluntary response (look away from the stimulus in the opposite direction). The impairments of HD patients in this task are mainly attributed to degeneration in the striatal medium spiny neurons leading to an over-activation of the indirect-pathway thorough the basal ganglia. However, some studies have proposed that damage outside the indirect-pathway also contribute to executive and saccade deficits. We used the interleaved pro- and anti-saccade task to study voluntary saccade inhibition deficits, Voxel-based morphometry and Tract-based spatial statistic to map cortico-basal ganglia circuitry atrophy in HD. HD patients had voluntary saccade inhibition control deficits, including increased regular-latency anti-saccade errors and increased anticipatory saccades. These deficits correlated with white-matter atrophy in the inferior fronto-occipital fasciculus, anterior thalamic radiation, anterior corona radiata and superior longitudinal fasciculus. These findings suggest that cortico-basal ganglia white-matter atrophy in HD, disrupts the normal connectivity in a network controlling voluntary saccade inhibitory behavior beyond the indirect-pathway. This suggests that in vivo measures of white-matter atrophy can be a reliable marker of the progression of cognitive deficits in HD.

  10. Rule-Based Categorization Deficits in Focal Basal Ganglia Lesion and Parkinson’s Disease Patients

    PubMed Central

    Ell, Shawn W.; Weinstein, Andrea; Ivry, Richard B.

    2010-01-01

    Patients with basal ganglia (BG) pathology are consistently found to be impaired on rule-based category learning tasks in which learning is thought to depend upon the use of an explicit, hypothesis-guided strategy. The factors that influence this impairment remain unclear. Moreover, it remains unknown if the impairments observed in patients with degenerative disorders such as Parkinson's disease (PD) are also observed in those with focal BG lesions. In the present study, we tested patients with either focal BG lesions or PD on two categorization tasks that varied in terms of their demands on selective attention and working memory. Individuals with focal BG lesions were impaired on the task in which working-memory demand was high and performed similarly to healthy controls on the task in which selective-attention demand was high. In contrast, individuals with PD were impaired on both tasks, and accuracy rates did not differ between on- and off-medication states for a subset of patients who were also tested after abstaining from dopaminergic medication. Quantitative, model-based analyses attributed the performance deficit for both groups in the task with high working-memory demand to the utilization of suboptimal strategies, whereas the PD-specific impairment on the task with high selective-attention demand was driven by the inconsistent use of an optimal strategy. These data suggest that the demands on selective attention and working memory affect the presence of impairment in patients with focal BG lesions and the nature of the impairment in patients with PD. PMID:20600196

  11. Monoclonal antibody (AFH1) immunoreactive on morphologically abnormal basal melanocytes within dysplastic nevi, nevocellular nevus nests, and melanoma.

    PubMed

    Aronson, P J; Ito, K; Fukaya, T; Hashimoto, K; Mehregan, A H

    1988-04-01

    The mouse monoclonal antibody AFH1 was produced using formalin-fixed, sham paraffin-embedded human melanoma cell culture line A375 as immunogen. Reactivity of this antibody was assessed by immunohistochemical techniques against formalin- or acid alcohol-fixed paraffin-embedded tissue as well as formalin- or acid alcohol-fixed unembedded lesions. Ninety-seven nevomelanocytic lesions, neurofibromas, epithelial lesions, and a plasmacellular infiltrate were evaluated. AFH1 was immunoreactive on 54 of 55 nevocytic lesions (98.2%), 15 of 16 primary melanomas (93.7%), a lentigo maligna, and nests in 21 of 21 dysplastic nevi (100%). Of 100 consecutive basal melanocytes of intraepidermal melanoma cells counted in each lesion, mean AFH1 immunoreactivity for nonnested basal melanocytes in nevocellular nevi was 3.8%; for dysplastic nevi, 13.8%; and for intraepidermal melanoma cells, 78.0%. When nonnested basal melanocytes were subdivided into cytologically normal and abnormal cell groups, AFH1 immunoreactivity was 9.4% and 72.6%, respectively. AFH1 recognition of the lentiginous portion of dysplastic nevi corresponds statistically to the appearance of abnormal melanocyte cytology, nest formation, or both. Using 50% immunoreactive nonnested melanocytes as the criterion, AFH1 seems to distinguish primary melanoma from dysplastic nevi with a sensitivity of 93.8% and a specificity of 95.8%.

  12. Interaction of oscillations, and their suppression via deep brain stimulation, in a model of the cortico-basal ganglia network.

    PubMed

    Kang, Guiyeom; Lowery, Madeleine M

    2013-03-01

    Growing evidence suggests that synchronized neural oscillations in the cortico-basal ganglia network may play a critical role in the pathophysiology of Parkinson's disease. In this study, a new model of the closed loop network is used to explore the generation and interaction of network oscillations and their suppression through deep brain stimulation (DBS). Under simulated dopamine depletion conditions, increased gain through the hyperdirect pathway resulted in the interaction of neural oscillations at different frequencies in the cortex and subthalamic nucleus (STN), leading to the emergence of synchronized oscillations at a new intermediate frequency. Further increases in synaptic gain resulted in the cortex driving synchronous oscillatory activity throughout the network. When DBS was added to the model a progressive reduction in STN power at the tremor and beta frequencies was observed as the frequency of stimulation was increased, with resonance effects occurring for low frequency DBS (40 Hz) in agreement with experimental observations. The results provide new insights into the mechanisms by which synchronous oscillations can arise within the network and how DBS may suppress unwanted oscillatory activity.

  13. Neonatal Brain MRI and Motor Outcome at School Age in Children with Neonatal Encephalopathy: A Review of Personal Experience

    PubMed Central

    Mercuri, Eugenio; Barnett, Anna L.

    2003-01-01

    The aim of this paper is to review (i) the spectrum of neuromotor function at school age in children who had been born full-term and presented with neonatal encephalopathy (NE) and low Apgar scores and (ii) the relation between the presence/absence of such difficulties and neonatal brain MRI. Motor outcome appears to be mainly related to the severity of basal ganglia and internal capsule involvement. Severe basal ganglia lesions were always associated with the most severe outcome, microcephaly, tetraplegia, and severe global delay, whereas more discrete basal ganglia lesions were associated with athetoid cerebral palsy, with normal cognitive development or minor neuro-motor abnormalities. White matter lesions were associated with abnormal motor outcome only if the internal capsule was involved. Children with moderate white matter changes but normal internal capsule, had normal motor outcome at school age. PMID:14640307

  14. Basal Ganglia Disorders Associated with Imbalances in the Striatal Striosome and Matrix Compartments

    PubMed Central

    Crittenden, Jill R.; Graybiel, Ann M.

    2011-01-01

    The striatum is composed principally of GABAergic, medium spiny striatal projection neurons (MSNs) that can be categorized based on their gene expression, electrophysiological profiles, and input–output circuits. Major subdivisions of MSN populations include (1) those in ventromedial and dorsolateral striatal regions, (2) those giving rise to the direct and indirect pathways, and (3) those that lie in the striosome and matrix compartments. The first two classificatory schemes have enabled advances in understanding of how basal ganglia circuits contribute to disease. However, despite the large number of molecules that are differentially expressed in the striosomes or the extra-striosomal matrix, and the evidence that these compartments have different input–output connections, our understanding of how this compartmentalization contributes to striatal function is still not clear. A broad view is that the matrix contains the direct and indirect pathway MSNs that form parts of sensorimotor and associative circuits, whereas striosomes contain MSNs that receive input from parts of limbic cortex and project directly or indirectly to the dopamine-containing neurons of the substantia nigra, pars compacta. Striosomes are widely distributed within the striatum and are thought to exert global, as well as local, influences on striatal processing by exchanging information with the surrounding matrix, including through interneurons that send processes into both compartments. It has been suggested that striosomes exert and maintain limbic control over behaviors driven by surrounding sensorimotor and associative parts of the striatal matrix. Consistent with this possibility, imbalances between striosome and matrix functions have been reported in relation to neurological disorders, including Huntington’s disease, L-DOPA-induced dyskinesias, dystonia, and drug addiction. Here, we consider how signaling imbalances between the striosomes and matrix might relate to symptomatology

  15. Motor cortex stimulation does not improve dystonia secondary to a focal basal ganglia lesion.

    PubMed

    Rieu, Isabelle; Aya Kombo, Magaly; Thobois, Stéphane; Derost, Philippe; Pollak, Pierre; Xie, Jing; Pereira, Bruno; Vidailhet, Marie; Burbaud, Pierre; Lefaucheur, Jean Pascal; Lemaire, Jean Jacques; Mertens, Patrick; Chabardes, Stephan; Broussolle, Emmanuel; Durif, Franck

    2014-01-14

    To assess the efficacy of epidural motor cortex stimulation (MCS) on dystonia, spasticity, pain, and quality of life in patients with dystonia secondary to a focal basal ganglia (BG) lesion. In this double-blind, crossover, multicenter study, 5 patients with dystonia secondary to a focal BG lesion were included. Two quadripolar leads were implanted epidurally over the primary motor (M1) and premotor cortices, contralateral to the most dystonic side. The leads were placed parallel to the central sulcus. Only the posterior lead over M1 was activated in this study. The most lateral or medial contact of the lead (depending on whether the dystonia predominated in the upper or lower limb) was selected as the anode, and the other 3 as cathodes. One month postoperatively, patients were randomly assigned to on- or off-stimulation for 3 months each, with a 1-month washout between the 2 conditions. Voltage, frequency, and pulse width were fixed at 3.8 V, 40 Hz, and 60 μs, respectively. Evaluations of dystonia (Burke-Fahn-Marsden Scale), spasticity (Ashworth score), pain intensity (visual analog scale), and quality of life (36-Item Short Form Health Survey) were performed before surgery and after each period of stimulation. Burke-Fahn-Marsden Scale, Ashworth score, pain intensity, and quality of life were not statistically significantly modified by MCS. Bipolar epidural MCS failed to improve any clinical feature in dystonia secondary to a focal BG lesion. This study provides Class I evidence that bipolar epidural MCS with the anode placed over the motor representation of the most affected limb failed to improve any clinical feature in dystonia secondary to a focal BG lesion.

  16. Tracking Deceased-Related Thinking with Neural Pattern Decoding of a Cortical-Basal Ganglia Circuit.

    PubMed

    Schneck, Noam; Haufe, Stefan; Tu, Tao; Bonanno, George A; Ochsner, Kevin; Sajda, Paul; Mann, J John

    2017-07-01

    Deceased-related thinking is central to grieving and potentially critical to processing of the loss. Self-report measurements might fail to capture important elements of deceased-related thinking and processing. Here, we used a machine learning approach applied to fMRI - known as neural decoding - to develop a measure of ongoing deceased-related processing. 23 subjects grieving the loss of a first-degree relative, spouse or partner within 14 months underwent two fMRI tasks. They first viewed pictures and stories related to the deceased, a living control and a demographic control figure while providing ongoing valence and arousal ratings. Second, they performed a 10-minute Sustained Attention to Response Task (SART) with thought probes every 25-35 seconds to identify deceased, living and self-related thoughts. A conjunction analysis, controlling for valence/arousal, identified neural clusters in basal ganglia, orbital prefrontal cortex and insula associated with both types of deceased-related stimuli vs. the two control conditions in the first task. This pattern was applied to fMRI data collected during the SART, and discriminated deceased-related but not living or self-related thoughts, independently of grief-severity and time since loss. Deceased-related thoughts on the SART correlated with self-reported avoidance. The neural model predicted avoidance over and above deceased-related thoughts. A neural pattern trained to identify mental representations of the deceased tracked deceased-related thinking during a sustained attention task and also predicted subject-level avoidance. This approach provides a new imaging tool to be used as an index of processing the deceased for future studies of complicated grief.

  17. [A case of neurofibromatosis type I associated with basal meningocele and abnormal vessels].

    PubMed

    Yoshioka, H; Sakoda, K; Kohno, H; Hada, H; Hanaya, R; Arita, K; Kurisu, K

    1998-03-01

    A 21-year-old man with neurofibromatosis type 1 (NF 1) had many widespread cutaneous neurofibroma on his right face. Magnetic resonance imaging (MRI) revealed basal meningocele due to dysplasia of the skull base. Carotid and vertebral angiograms revealed occlusion of the right internal carotid artery, persistent primitive trigeminal artery. We have reviewed the clinical and radiographic features of this case of neurofibromatosis, meningocele and cerebral arterial abnormalities. NF associated with both intracranial vascular malformation and meningocele is very rare, and in our case both were thought to arise congenitally as a manifestation of mesodermal dysplasia. Careful follow up using MRI and MR angiography should be performed for such patients.

  18. The relative phases of basal ganglia activities dynamically shape effective connectivity in Parkinson's disease.

    PubMed

    Cagnan, Hayriye; Duff, Eugene Paul; Brown, Peter

    2015-06-01

    Optimal phase alignment between oscillatory neural circuits is hypothesized to optimize information flow and enhance system performance. This theory is known as communication-through-coherence. The basal ganglia motor circuit exhibits exaggerated oscillatory and coherent activity patterns in Parkinson's disease. Such activity patterns are linked to compromised motor system performance as evinced by bradykinesia, rigidity and tremor, suggesting that network function might actually deteriorate once a certain level of net synchrony is exceeded in the motor circuit. Here, we characterize the processes underscoring excessive synchronization and its termination. To this end, we analysed local field potential recordings from the subthalamic nucleus and globus pallidus of five patients with Parkinson's disease (four male and one female, aged 37-64 years). We observed that certain phase alignments between subthalamic nucleus and globus pallidus amplified local neural synchrony in the beta frequency band while others either suppressed it or did not induce any significant change with respect to surrogates. The increase in local beta synchrony directly correlated with how long the two nuclei locked to beta-amplifying phase alignments. Crucially, administration of the dopamine prodrug, levodopa, reduced the frequency and duration of periods during which subthalamic and pallidal populations were phase-locked to beta-amplifying alignments. Conversely ON dopamine, the total duration over which subthalamic and pallidal populations were aligned to phases that left beta-amplitude unchanged with respect to surrogates increased. Thus dopaminergic input shifted circuit dynamics from persistent periods of locking to amplifying phase alignments, associated with compromised motoric function, to more dynamic phase alignment and improved motoric function. This effect of dopamine on local circuit resonance suggests means by which novel electrical interventions might prevent resonance

  19. Function of basal ganglia in bridging cognitive and motor modules to perform an action

    PubMed Central

    Nagano-Saito, Atsuko; Martinu, Kristina; Monchi, Oury

    2014-01-01

    The basal ganglia (BG) are thought to be involved in the integration of multiple sources of information, and their dysfunction can lead to disorders such as Parkinson's disease (PD). PD patients show motor and cognitive dysfunction with specific impairments in the internal generation of motor actions and executive deficits, respectively. The role of the BG, then, would be to integrate information from several sources in order to make a decision on a resulting action adequate for the required task. Reanalyzing the data set from our previous study (Martinu et al., 2012), we investigated this hypothesis by applying a graph theory method to a series of fMRI data during the performance of self-initiated (SI) finger movement tasks obtained in healthy volunteers (HV) and early stage PD patients. Dorsally, connectivity strength between the medial prefrontal areas (mPFC) and cortical regions including the primary motor area (M1), the extrastriate visual cortex, and the associative cortex, was reduced in the PD patients. The connectivity strengths were positively correlated to activity in the striatum in both groups. Ventrally, all connectivity between the striatum, the thalamus, and the extrastriate visual cortex decreased in strength in the PD, as did the connectivity between the striatum and the ventrolateral PFC (VLPFC). Individual response time (RT) was negatively correlated to connectivity strength between the dorsolateral PFC (DLPFC) and the striatum and positively correlated to connectivity between the VLPFC and the striatum in the HV. These results indicate that the BG, with the mPFC and thalamus, are involved in integrating multiple sources of information from areas such as DLPFC, and VLPFC, connecting to M1, thereby determining a network that leads to the adequate decision and performance of the resulting action. PMID:25071432

  20. Social modulation of learned behavior by dopamine in the basal ganglia: insights from songbirds.

    PubMed

    Leblois, Arthur

    2013-06-01

    Dysfunction of the dopaminergic system leads to motor, cognitive, and motivational symptoms in brain disorders such as Parkinson's disease. The basal ganglia (BG) are involved in sensorimotor learning and receive a strong dopaminergic signal, shown to play an important role in social interactions. The function of the dopaminergic input to the BG in the integration of social cues during sensorimotor learning remains however largely unexplored. Songbirds use learned vocalizations to communicate during courtship and aggressive behaviors. Like language learning in humans, song learning strongly depends on social interactions. In songbirds, a specialized BG-thalamo-cortical loop devoted to song is particularly tractable for elucidating the signals carried by dopamine in the BG, and the function of dopamine signaling in mediating social cues during skill learning and execution. Here, I review experimental findings uncovering the physiological effects and function of the dopaminergic signal in the songbird BG, in light of our knowledge of the BG-dopamine interactions in mammals. Interestingly, the compact nature of the striato-pallidal circuits in birds led to new insight on the physiological effects of the dopaminergic input on the BG network as a whole. In singing birds, D1-like receptor agonist and antagonist can modulate the spectral variability of syllables bi-directionally, suggesting that social context-dependent changes in spectral variability are triggered by dopaminergic input through D1-like receptors. As variability is crucial for exploration during motor learning, but must be reduced after learning to optimize performance, I propose that, the dopaminergic input to the BG could be responsible for the social-dependent regulation of the exploration/exploitation balance in birdsong, and possibly in learned skills in other vertebrates. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Cortico-basal ganglia networks subserving goal-directed behavior mediated by conditional visuo-goal association

    PubMed Central

    Hoshi, Eiji

    2013-01-01

    Action is often executed according to information provided by a visual signal. As this type of behavior integrates two distinct neural representations, perception and action, it has been thought that identification of the neural mechanisms underlying this process will yield deeper insights into the principles underpinning goal-directed behavior. Based on a framework derived from conditional visuomotor association, prior studies have identified neural mechanisms in the dorsal premotor cortex (PMd), dorsolateral prefrontal cortex (dlPFC), ventrolateral prefrontal cortex (vlPFC), and basal ganglia (BG). However, applications resting solely on this conceptualization encounter problems related to generalization and flexibility, essential processes in executive function, because the association mode involves a direct one-to-one mapping of each visual signal onto a particular action. To overcome this problem, we extend this conceptualization and postulate a more general framework, conditional visuo-goal association. According to this new framework, the visual signal identifies an abstract behavioral goal, and an action is subsequently selected and executed to meet this goal. Neuronal activity recorded from the four key areas of the brains of monkeys performing a task involving conditional visuo-goal association revealed three major mechanisms underlying this process. First, visual-object signals are represented primarily in the vlPFC and BG. Second, all four areas are involved in initially determining the goals based on the visual signals, with the PMd and dlPFC playing major roles in maintaining the salience of the goals. Third, the cortical areas play major roles in specifying action, whereas the role of the BG in this process is restrictive. These new lines of evidence reveal that the four areas involved in conditional visuomotor association contribute to goal-directed behavior mediated by conditional visuo-goal association in an area-dependent manner. PMID:24155692

  2. Gd-based Contrast Enhancement of the Perivascular Spaces in the Basal Ganglia.

    PubMed

    Naganawa, Shinji; Nakane, Toshiki; Kawai, Hisashi; Taoka, Toshiaki

    2017-01-10

    In textbooks, the perivascular space (PVS) is described as non-enhancing after the intravenous administration of gadolinium-based contrast agent (IV-GBCA). We noticed that the PVS sometimes has high signal intensity (SI) on heavily T 2 -weighted 3D-FLAIR (hT 2 -FL) images obtained 4 h after IV-GBCA. The purpose of this study was to retrospectively evaluate the contrast enhancement of the PVS. In 8 healthy subjects and 19 patients with suspected endolymphatic hydrops, magnetic resonance cisternography (MRC) and hT 2 -FL images were obtained before and 4 h after a single dose of IV-GBCA. No subjects had renal insufficiency. On axial MRC at the level of the anterior commissure (AC)-posterior commissure (PC) line, 1 cm circular regions of interest (ROIs) were drawn centering on the PVS in the bilateral basal ganglia and thalami. Three-millimeter diameter ROIs were set in the cerebrospinal fluid (CSF) of the bilateral ambient cistern. The ROIs on MRC were copied onto the hT 2 -FL images and the SI was measured. The SI ratio (SIR) was defined as SIR PVS = SI of PVS/SI of the thalami, and SIR CSF = SI of CSF/SI of the thalami. The average of the bilateral values was used for the calculation. The SIR CSF , SIR PVS , and SI of the thalami were compared between before and 4 h after IV-GBCA. The SIR was increased significantly from 1.02 ± 0.37 to 2.65 ± 0.82 in the CSF (P < 0.01) and from 1.20 ± 0.35 to 2.13 ± 1.23 in the PVS at 4 h after IV-GBCA (P < 0.01). The SI of the thalami showed no significant difference. The enhancement of the PVS at 4 h after IV-GBCA was confirmed even in subjects without renal insufficiency. It is possible that the GBCA in the blood vessels might have permeated into the cerebrospinal fluid (CSF) space and the PVS. This might be a first step in the imaging evaluation of the glymphatic system (waste clearance system) of the brain.

  3. Gd-based Contrast Enhancement of the Perivascular Spaces in the Basal Ganglia

    PubMed Central

    Naganawa, Shinji; Nakane, Toshiki; Kawai, Hisashi; Taoka, Toshiaki

    2017-01-01

    Purpose: In textbooks, the perivascular space (PVS) is described as non-enhancing after the intravenous administration of gadolinium-based contrast agent (IV-GBCA). We noticed that the PVS sometimes has high signal intensity (SI) on heavily T2-weighted 3D-FLAIR (hT2-FL) images obtained 4 h after IV-GBCA. The purpose of this study was to retrospectively evaluate the contrast enhancement of the PVS. Materials and Methods: In 8 healthy subjects and 19 patients with suspected endolymphatic hydrops, magnetic resonance cisternography (MRC) and hT2-FL images were obtained before and 4 h after a single dose of IV-GBCA. No subjects had renal insufficiency. On axial MRC at the level of the anterior commissure (AC)-posterior commissure (PC) line, 1 cm circular regions of interest (ROIs) were drawn centering on the PVS in the bilateral basal ganglia and thalami. Three-millimeter diameter ROIs were set in the cerebrospinal fluid (CSF) of the bilateral ambient cistern. The ROIs on MRC were copied onto the hT2-FL images and the SI was measured. The SI ratio (SIR) was defined as SIRPVS = SI of PVS/SI of the thalami, and SIRCSF = SI of CSF/SI of the thalami. The average of the bilateral values was used for the calculation. The SIRCSF, SIRPVS, and SI of the thalami were compared between before and 4 h after IV-GBCA. Results: The SIR was increased significantly from 1.02 ± 0.37 to 2.65 ± 0.82 in the CSF (P < 0.01) and from 1.20 ± 0.35 to 2.13 ± 1.23 in the PVS at 4 h after IV-GBCA (P < 0.01). The SI of the thalami showed no significant difference. Conclusion: The enhancement of the PVS at 4 h after IV-GBCA was confirmed even in subjects without renal insufficiency. It is possible that the GBCA in the blood vessels might have permeated into the cerebrospinal fluid (CSF) space and the PVS. This might be a first step in the imaging evaluation of the glymphatic system (waste clearance system) of the brain. PMID:27430361

  4. Widespread abnormality of the γ-aminobutyric acid-ergic system in Tourette syndrome

    PubMed Central

    Bagic, Anto; Simmons, Janine M.; Mari, Zoltan; Bonne, Omer; Xu, Ben; Kazuba, Diane; Herscovitch, Peter; Carson, Richard E.; Murphy, Dennis L.; Drevets, Wayne C.; Hallett, Mark

    2012-01-01

    Dysfunction of the γ-aminobutyric acid-ergic system in Tourette syndrome may conceivably underlie the symptoms of motor disinhibition presenting as tics and psychiatric manifestations, such as attention deficit hyperactivity disorder and obsessive–compulsive disorder. The purpose of this study was to identify a possible dysfunction of the γ-aminobutyric acid-ergic system in Tourette patients, especially involving the basal ganglia-thalamo-cortical circuits and the cerebellum. We studied 11 patients with Tourette syndrome and 11 healthy controls. Positron emission tomography procedure: after injection of 20 mCi of [11C]flumazenil, dynamic emission images of the brain were acquired. Structural magnetic resonance imaging scans were obtained to provide an anatomical framework for the positron emission tomography data analysis. Images of binding potential were created using the two-step version of the simplified reference tissue model. The binding potential images then were spatially normalized, smoothed and compared between groups using statistical parametric mapping. We found decreased binding of GABAA receptors in Tourette patients bilaterally in the ventral striatum, globus pallidus, thalamus, amygdala and right insula. In addition, the GABAA receptor binding was increased in the bilateral substantia nigra, left periaqueductal grey, right posterior cingulate cortex and bilateral cerebellum. These results are consistent with the longstanding hypothesis that circuits involving the basal ganglia and thalamus are disinhibited in Tourette syndrome patients. In addition, the abnormalities in GABAA receptor binding in the insula and cerebellum appear particularly noteworthy based upon recent evidence implicating these structures in the generation of tics. PMID:22577221

  5. Integration of cortical and pallidal inputs in the basal ganglia-recipient thalamus of singing birds

    PubMed Central

    Goldberg, Jesse H.; Farries, Michael A.

    2012-01-01

    The basal ganglia-recipient thalamus receives inhibitory inputs from the pallidum and excitatory inputs from cortex, but it is unclear how these inputs interact during behavior. We recorded simultaneously from thalamic neurons and their putative synaptically connected pallidal inputs in singing zebra finches. We find, first, that each pallidal spike produces an extremely brief (∼5 ms) pulse of inhibition that completely suppresses thalamic spiking. As a result, thalamic spikes are entrained to pallidal spikes with submillisecond precision. Second, we find that the number of thalamic spikes that discharge within a single pallidal interspike interval (ISI) depends linearly on the duration of that interval but does not depend on pallidal activity prior to the interval. In a detailed biophysical model, our results were not easily explained by the postinhibitory “rebound” mechanism previously observed in anesthetized birds and in brain slices, nor could most of our data be characterized as “gating” of excitatory transmission by inhibitory pallidal input. Instead, we propose a novel “entrainment” mechanism of pallidothalamic transmission that highlights the importance of an excitatory conductance that drives spiking, interacting with brief pulses of pallidal inhibition. Building on our recent finding that cortical inputs can drive syllable-locked rate modulations in thalamic neurons during singing, we report here that excitatory inputs affect thalamic spiking in two ways: by shortening the latency of a thalamic spike after a pallidal spike and by increasing thalamic firing rates within individual pallidal ISIs. We present a unifying biophysical model that can reproduce all known modes of pallidothalamic transmission—rebound, gating, and entrainment—depending on the amount of excitation the thalamic neuron receives. PMID:22673333

  6. Psychological intervention with working memory training increases basal ganglia volume: A VBM study of inpatient treatment for methamphetamine use.

    PubMed

    Brooks, S J; Burch, K H; Maiorana, S A; Cocolas, E; Schioth, H B; Nilsson, E K; Kamaloodien, K; Stein, D J

    2016-01-01

    Protracted methamphetamine (MA) use is associated with decreased control over drug craving and altered brain volume in the frontostriatal network. However, the nature of volumetric changes following a course of psychological intervention for MA use is not yet known. 66 males (41 MA patients, 25 healthy controls, HC) between the ages of 18-50 were recruited, the MA patients from new admissions to an in-patient drug rehabilitation centre and the HC via public advertisement, both in Cape Town, South Africa. 17 MA patients received 4 weeks of treatment as usual (TAU), and 24 MA patients completed TAU plus daily 30-minute cognitive training (CT) using an N-back working memory task. Magnetic resonance imaging (MRI) at baseline and 4-week follow-up was acquired and voxel-based morphometry (VBM) was used for analysis. TAU was associated with larger bilateral striatum (caudate/putamen) volume, whereas CT was associated with more widespread increases of the bilateral basal ganglia (incorporating the amygdala and hippocampus) and reduced bilateral cerebellum volume coinciding with improvements in impulsivity scores. While psychological intervention is associated with larger volume in mesolimbic reward regions, the utilisation of additional working memory training as an adjunct to treatment may further normalize frontostriatal structure and function.

  7. Kir2 potassium channels in rat striatum are strategically localized to control basal ganglia function.

    PubMed

    Prüss, Harald; Wenzel, Mareike; Eulitz, Dirk; Thomzig, Achim; Karschin, Andreas; Veh, Rüdiger W

    2003-02-20

    Parkinson's disease is the most frequent movement disorder caused by loss of dopaminergic neurons in the midbrain. Intentions to avoid side effects of the conventional therapy should aim to identify additional targets for potential pharmacological intervention. In principle, every step of a signal transduction cascade such as presynaptic transmitter release, type and occupation of postsynaptic receptors, G protein-mediated effector mechanisms, and the alterations of pre- or postsynaptic potentials as determined by the local ion channel composition, have to be considered. Due to their diversity and their widespread but distinct localizations, potassium channels represent interesting candidates for new therapeutic strategies. As a first step, the present report aimed to study in the striatum the cellular and subcellular distribution of the individual members of the Kir2 family, a group of proteins forming inwardly rectifying potassium channels. For this purpose polyclonal monospecific affinity-purified antibodies against the less conserved carboxyterminal sequences from the Kir2.1, Kir2.2, Kir2.3, and Kir2.4 proteins were prepared. All subunits of the Kir2 family were detected on somata and dendrites of most striatal neurons. However, the distribution of two of them was not homogeneous. Striatal patch areas were largely devoid of the Kir2.3 protein, and the Kir2.4 subunit was most prominently expressed on the tonically active, giant cholinergic interneurons of the striatum. These two structures are among the key players in regulating dopaminergic and cholinergic neurotransmission within the striatum, and therefore are of major importance for the output of the basal ganglia. The heterogeneous localization of the Kir2.3 and the Kir2.4 subunits with respect to these strategic structures pinpoints to these channel proteins as promising targets for future pharmacological efforts.

  8. The role of cortical oscillations in a spiking neural network model of the basal ganglia.

    PubMed

    Fountas, Zafeirios; Shanahan, Murray

    2017-01-01

    Although brain oscillations involving the basal ganglia (BG) have been the target of extensive research, the main focus lies disproportionally on oscillations generated within the BG circuit rather than other sources, such as cortical areas. We remedy this here by investigating the influence of various cortical frequency bands on the intrinsic effective connectivity of the BG, as well as the role of the latter in regulating cortical behaviour. To do this, we construct a detailed neural model of the complete BG circuit based on fine-tuned spiking neurons, with both electrical and chemical synapses as well as short-term plasticity between structures. As a measure of effective connectivity, we estimate information transfer between nuclei by means of transfer entropy. Our model successfully reproduces firing and oscillatory behaviour found in both the healthy and Parkinsonian BG. We found that, indeed, effective connectivity changes dramatically for different cortical frequency bands and phase offsets, which are able to modulate (or even block) information flow in the three major BG pathways. In particular, alpha (8-12Hz) and beta (13-30Hz) oscillations activate the direct BG pathway, and favour the modulation of the indirect and hyper-direct pathways via the subthalamic nucleus-globus pallidus loop. In contrast, gamma (30-90Hz) frequencies block the information flow from the cortex completely through activation of the indirect pathway. Finally, below alpha, all pathways decay gradually and the system gives rise to spontaneous activity generated in the globus pallidus. Our results indicate the existence of a multimodal gating mechanism at the level of the BG that can be entirely controlled by cortical oscillations, and provide evidence for the hypothesis of cortically-entrained but locally-generated subthalamic beta activity. These two findings suggest new insights into the pathophysiology of specific BG disorders.

  9. The role of cortical oscillations in a spiking neural network model of the basal ganglia

    PubMed Central

    Fountas, Zafeirios; Shanahan, Murray

    2017-01-01

    Although brain oscillations involving the basal ganglia (BG) have been the target of extensive research, the main focus lies disproportionally on oscillations generated within the BG circuit rather than other sources, such as cortical areas. We remedy this here by investigating the influence of various cortical frequency bands on the intrinsic effective connectivity of the BG, as well as the role of the latter in regulating cortical behaviour. To do this, we construct a detailed neural model of the complete BG circuit based on fine-tuned spiking neurons, with both electrical and chemical synapses as well as short-term plasticity between structures. As a measure of effective connectivity, we estimate information transfer between nuclei by means of transfer entropy. Our model successfully reproduces firing and oscillatory behaviour found in both the healthy and Parkinsonian BG. We found that, indeed, effective connectivity changes dramatically for different cortical frequency bands and phase offsets, which are able to modulate (or even block) information flow in the three major BG pathways. In particular, alpha (8–12Hz) and beta (13–30Hz) oscillations activate the direct BG pathway, and favour the modulation of the indirect and hyper-direct pathways via the subthalamic nucleus—globus pallidus loop. In contrast, gamma (30–90Hz) frequencies block the information flow from the cortex completely through activation of the indirect pathway. Finally, below alpha, all pathways decay gradually and the system gives rise to spontaneous activity generated in the globus pallidus. Our results indicate the existence of a multimodal gating mechanism at the level of the BG that can be entirely controlled by cortical oscillations, and provide evidence for the hypothesis of cortically-entrained but locally-generated subthalamic beta activity. These two findings suggest new insights into the pathophysiology of specific BG disorders. PMID:29236724

  10. Dissociation of functional and anatomical brain abnormalities in unaffected siblings of schizophrenia patients.

    PubMed

    Guo, Wenbin; Song, Yan; Liu, Feng; Zhang, Zhikun; Zhang, Jian; Yu, Miaoyu; Liu, Jianrong; Xiao, Changqing; Liu, Guiying; Zhao, Jingping

    2015-05-01

    Schizophrenia patients and their unaffected siblings share similar brain functional and structural abnormalities. However, no study is engaged to investigate whether and how functional abnormalities are related to structural abnormalities in unaffected siblings. This study was undertaken to examine the association between functional and anatomical abnormalities in unaffected siblings. Forty-six unaffected siblings of schizophrenia patients and 46 age-, sex-, and education-matched healthy controls underwent structural and resting-state functional magnetic resonance imaging scanning. Voxel-based morphometry (VBM), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were utilized to analyze imaging data. The VBM analysis showed gray matter volume decreases in the fronto-temporal regions (the left middle temporal gyrus and right inferior frontal gyrus, orbital part) and increases in basal ganglia system (the left putamen). Functional abnormalities measured by ALFF and fALFF mainly involved in the fronto-limbic-sensorimotor circuit (decreased ALFF in bilateral middle frontal gyrus and the right middle cingulate gyrus, and decreased fALFF in the right inferior frontal gyrus, orbital part; and increased ALFF in the left fusiform gyrus and left lingual gyrus, and increased fALFF in bilateral calcarine cortex). No significant correlation was found between functional and anatomical abnormalities in the sibling group. A dissociation pattern of brain regions with functional and anatomical abnormalities is observed in unaffected siblings. Our findings suggest that brain functional and anatomical abnormalities might be present independently in unaffected siblings of schizophrenia patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  11. Alteration of Basal Ganglia and Right Frontoparietal Network in Early Drug-Naïve Parkinson's Disease during Heat Pain Stimuli and Resting State.

    PubMed

    Tan, Ying; Tan, Juan; Deng, Jiayan; Cui, Wenjuan; He, Hui; Yang, Fei; Deng, Hongjie; Xiao, Ruhui; Huang, Zhengkuan; Zhang, Xingxing; Tan, Rui; Shen, Xiaotao; Liu, Tao; Wang, Xiaoming; Yao, Dezhong; Luo, Cheng

    2015-01-01

    The symptoms and pathogenesis of Parkinson's disease (PD) are complicated and an accurate diagnosis of PD is difficult, particularly in early-stage. Because functional magnetic resonance imaging (fMRI) is non-invasive and is characterized by the integration of different brain areas in terms of functional connectivity (FC), fMRI has been widely used in PD research. Non-motor symptom (NMS) features are also frequently present in PD before the onset of classical motor symptoms with pain as the primary NMS. Considering that PD could affect the pain process at multiple levels, we hypothesized that pain is one of the earliest symptoms in PD and investigated whether FC of the pain network was disrupted in PD without pain. To better understand the pathogenesis of pain in PD, we combined resting state and pain-stimuli-induced task state fMRI to identify alterations in FC related to pain in PD. Fourteen early drug-naïve PD without pain and 17 age- and sex-matched healthy controls (HC) participated in our testing task. We used independent component analysis to select seven functional networks related to PD and pain. We focused on abnormalities in FC and in functional network connectivity (FNC) in PD compared with HC during the task (51°C heat pain stimuli) and at rest. Compared with HC, PD showed decreased FC in putamen within basal ganglia network (BGN) in task state and decreased FC in putamen of salience network (SN) and mid-cingulate cortex of sensorimotor network in rest state. FNC between the BGN and the SN are reduced during both states in PD compared with HC. In addition, right frontoparietal network (RFPN), which is considered as a bridge between the SN and default-mode network, was significantly disturbed during the task. These findings suggest that BGN plays a role in the pathological mechanisms of pain underlying PD, and RFPN likely contributes greatly to harmonization between intrinsic brain activity and external stimuli.

  12. Higher ambulatory systolic blood pressure independently associated with enlarged perivascular spaces in basal ganglia.

    PubMed

    Yang, Shuna; Yuan, Junliang; Zhang, Xiaoyu; Fan, Huimin; Li, Yue; Yin, Jiangmei; Hu, Wenli

    2017-09-01

    Enlarged perivascular spaces (EPVS) have been identified as a marker of cerebral small vessel diseases (CSVD). Ambulatory blood pressure (ABP) is the strongest predictor of hypertension-related brain damage. However, the relationship between ABP levels and EPVS is unclear. This study aimed to investigate the association between ABP levels and EPVS by 24-hour ambulatory blood pressure monitoring (ABPM). We prospectively recruited inpatients for physical examinations in our hospital from May 2013 to Jun 2016. 24-hour ABPM data and cranial magnetic resonance imaging information were collected. EPVS in basal ganglia (BG) and centrum semiovale (CSO) were identified and classified into three categories by the severity. White matter hyperintensities were scored by Fazekas scale. Spearman correlation analysis and multiple logistic regression analysis were used to determine the relationship between ABP levels and EPVS. A total of 573 subjects were enrolled in this study. 24-hour, day and night systolic blood pressure (SBP) levels were positively related to higher numbers of EPVS in BG (24-hour SBP: r = 0.23, p < 0.01; day SBP: r = 0.25, p < 0.01; night SBP: r = 0.30, p < 0.01). The association was unchanged after controlling for confounders by multiple logistic regression analysis. 24-hour and day diastolic blood pressure (DBP) levels increased with an increasing degree of EPVS in CSO (p = 0.04 and 0.049, respectively). But the association disappeared after adjusting for confounders. Spearman correlation analysis indicated that ABP levels were not associated with higher numbers of EPVS in CSO (p > 0.05). DBP levels were not independently associated with the severity of EPVS in BG and CSO. Higher SBP levels were independently associated with EPVS in BG, but not in CSO, which supported EPVS in BG to be a marker of CSVD. Pathogenesis of EPVS in BG and CSO might be different.

  13. Basal ganglia and gait control: apomorphine administration and internal pallidum stimulation in Parkinson's disease.

    PubMed

    Grasso, R; Peppe, A; Stratta, F; Angelini, D; Zago, M; Stanzione, P; Lacquaniti, F

    1999-05-01

    Gait coordination was analyzed (four-camera 100 Hz ELITE system) in two groups of idiopathic Parkinson disease (PD) patients. Five patients underwent continuous infusion of apomorphine and were recorded in two different sessions (APO OFF and APO ON) in the same day. Three patients with a previous chronic electrode implantation in both internal globi pallidi (GPi) were recorded in the same experimental session with the electrodes on and off (STIM ON and STIM OFF). The orientation of both the trunk and the lower-limb segments was described with respect to the vertical in the sagittal plane. Lower-limb inter-segmental coordination was evaluated by analyzing the co-variation between thigh, shank, and foot elevation angles by means of orthogonal planar regression. At least 30 gait cycles per experimental condition were processed. We found that the trunk was bent forward in STIM OFF, whereas it was better aligned with the vertical in STIM ON in both PD groups. The legs never fully extended during the gait cycle in STIM OFF, whereas they extended before heel strike in STIM ON. The multisegmental coordination of the lower limb changed almost in parallel with the changes in trunk orientation. In STIM OFF, both the shape and the spatial orientation of the planar gait loops (thigh angle vs. shank angle vs. foot angle) differed from those of physiological locomotion, whereas in STIM ON the gait loop tended to resume features closer to the control. Switching the electrodes on and off in patients with GPi electrodes resulted in quasi-parallel changes of the trunk inclination and of the planar gait loop. The bulk of the data suggest that the basal-ganglia circuitry may be relevant in locomotion by providing an appropriate spatio-temporal framework for the control of posture and movement in a gravity-based body-centered frame of reference. Pallido-thalamic and/or pallido-mesencephalic pathways may influence the timing of the inter-segmental coordination for gait.

  14. The development of repetitive motor behaviors in deer mice: Effects of environmental enrichment, repeated testing, and differential mediation by indirect basal ganglia pathway activation

    PubMed Central

    Bechard, Allison R.; Bliznyuk, Nikolay; Lewis, Mark H.

    2017-01-01

    Little is known about the mechanisms mediating the development of repetitive behaviors in human or animals. Deer mice reared with environmental enrichment (EE) exhibit fewer repetitive behaviors and greater indirect basal ganglia pathway activation as adults than those reared in standard cages. The developmental progression of these behavioral and neural circuitry changes has not been characterized. We assessed the development of repetitive behavior in deer mice using both a longitudinal and cohort design. Repeated testing negated the expected effect of EE, but cohort analyses showed that progression of repetitive behavior was arrested after one week of EE and differed significantly from controls after 3 weeks. Moreover, EE reductions in repetitive behavior were associated with increasing activation of indirect pathway nuclei in males across adolescence, but not females. These findings provide the first assessment of developmental trajectories within EE and support indirect pathway mediation of repetitive behavior in male deer mice. PMID:28181216

  15. Massive Submucosal Ganglia in Colonic Inertia.

    PubMed

    Naemi, Kaveh; Stamos, Michael J; Wu, Mark Li-Cheng

    2018-02-01

    - Colonic inertia is a debilitating form of primary chronic constipation with unknown etiology and diagnostic criteria, often requiring pancolectomy. We have occasionally observed massively enlarged submucosal ganglia containing at least 20 perikarya, in addition to previously described giant ganglia with greater than 8 perikarya, in cases of colonic inertia. These massively enlarged ganglia have yet to be formally recognized. - To determine whether such "massive submucosal ganglia," defined as ganglia harboring at least 20 perikarya, characterize colonic inertia. - We retrospectively reviewed specimens from colectomies of patients with colonic inertia and compared the prevalence of massive submucosal ganglia occurring in this setting to the prevalence of massive submucosal ganglia occurring in a set of control specimens from patients lacking chronic constipation. - Seven of 8 specimens affected by colonic inertia harbored 1 to 4 massive ganglia, for a total of 11 massive ganglia. One specimen lacked massive ganglia but had limited sampling and nearly massive ganglia. Massive ganglia occupied both superficial and deep submucosal plexus. The patient with 4 massive ganglia also had 1 mitotically active giant ganglion. Only 1 massive ganglion occupied the entire set of 10 specimens from patients lacking chronic constipation. - We performed the first, albeit distinctly small, study of massive submucosal ganglia and showed that massive ganglia may be linked to colonic inertia. Further, larger studies are necessary to determine whether massive ganglia are pathogenetic or secondary phenomena, and whether massive ganglia or mitotically active ganglia distinguish colonic inertia from other types of chronic constipation.

  16. Safinamide Differentially Modulates In Vivo Glutamate and GABA Release in the Rat Hippocampus and Basal Ganglia.

    PubMed

    Morari, Michele; Brugnoli, Alberto; Pisanò, Clarissa Anna; Novello, Salvatore; Caccia, Carla; Melloni, Elsa; Padoani, Gloria; Vailati, Silvia; Sardina, Marco

    2018-02-01

    Safinamide has been recently approved as an add-on to levodopa therapy for Parkinson disease. In addition to inhibiting monoamine oxidase type B, it blocks sodium channels and modulates glutamate (Glu) release in vitro. Since this property might contribute to the therapeutic action of the drug, we undertook the present study to investigate whether safinamide inhibits Glu release also in vivo and whether this effect is consistent across different brain areas and is selective for glutamatergic neurons. To this aim, in vivo microdialysis was used to monitor the spontaneous and veratridine-induced Glu and GABA release in the hippocampus and basal ganglia of naive, awake rats. Brain levels of safinamide were measured as well. To shed light on the mechanisms underlying the effect of safinamide, sodium currents were measured by patch-clamp recording in rat cortical neurons. Safinamide maximally inhibited the veratridine-induced Glu and GABA release in hippocampus at 15 mg/kg, which reached free brain concentrations of 1.89-1.37 µ M. This dose attenuated veratridine-stimulated Glu (but not GABA) release in subthalamic nucleus, globus pallidus, and substantia nigra reticulata, but not in striatum. Safinamide was ineffective on spontaneous neurotransmitter release. In vitro, safinamide inhibited sodium channels, showing a greater affinity at depolarized (IC 50 = 8 µ M) than at resting (IC 50 = 262 µ M) potentials. We conclude that safinamide inhibits in vivo Glu release from stimulated nerve terminals, likely via blockade of sodium channels at subpopulations of neurons with specific firing patterns. These data are consistent with the anticonvulsant and antiparkinsonian actions of safinamide and provide support for the nondopaminergic mechanism of its action. Copyright © 2018 The Author(s).

  17. Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease.

    PubMed

    Lammers, Nicolette M; Sondermeijer, Brigitte M; Twickler, Th B Marcel; de Bie, Rob M; Ackermans, Mariëtte T; Fliers, Eric; Schuurman, P Richard; La Fleur, Susanne E; Serlie, Mireille J

    2014-01-01

    Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans.

  18. Recurrent interactions between the input and output of a songbird cortico-basal ganglia pathway are implicated in vocal sequence variability

    PubMed Central

    Hamaguchi, Kosuke; Mooney, Richard

    2012-01-01

    Complex brain functions, such as the capacity to learn and modulate vocal sequences, depend on activity propagation in highly distributed neural networks. To explore the synaptic basis of activity propagation in such networks, we made dual in vivo intracellular recordings in anesthetized zebra finches from the input (nucleus HVC) and output (lateral magnocellular nucleus of the anterior nidopallium (LMAN)) neurons of a songbird cortico-basal ganglia (BG) pathway necessary to the learning and modulation of vocal motor sequences. These recordings reveal evidence of bidirectional interactions, rather than only feedforward propagation of activity from HVC to LMAN, as had been previously supposed. A combination of dual and triple recording configurations and pharmacological manipulations was used to map out circuitry by which activity propagates from LMAN to HVC. These experiments indicate that activity travels to HVC through at least two independent ipsilateral pathways, one of which involves fast signaling through a midbrain dopaminergic cell group, reminiscent of recurrent mesocortical loops described in mammals. We then used in vivo pharmacological manipulations to establish that augmented LMAN activity is sufficient to restore high levels of sequence variability in adult birds, suggesting that recurrent interactions through highly distributed forebrain – midbrain pathways can modulate learned vocal sequences. PMID:22915110

  19. [Emotion and basal ganglia (II): what can we learn from subthalamic nucleus deep brain stimulation in Parkinson's disease?].

    PubMed

    Péron, J; Dondaine, T

    2012-01-01

    The subthalamic nucleus deep-brain stimulation Parkinson's disease patient model seems to represent a unique opportunity for studying the functional role of the basal ganglia and notably the subthalamic nucleus in human emotional processing. Indeed, in addition to constituting a therapeutic advance for severely disabled Parkinson's disease patients, deep brain stimulation is a technique, which selectively modulates the activity of focal structures targeted by surgery. There is growing evidence of a link between emotional impairments and deep-brain stimulation of the subthalamic nucleus. In this context, according to the definition of emotional processing exposed in the companion paper available in this issue, the aim of the present review will consist in providing a synopsis of the studies that investigated the emotional disturbances observed in subthalamic nucleus deep brain stimulation Parkinson's disease patients. This review leads to the conclusion that several emotional components would be disrupted after subthalamic nucleus deep brain stimulation in Parkinson's disease: subjective feeling, neurophysiological activation, and motor expression. Finally, after a description of the limitations of this study model, we discuss the functional role of the subthalamic nucleus (and the striato-thalamo-cortical circuits in which it is involved) in emotional processing. It seems reasonable to conclude that the striato-thalamo-cortical circuits are indeed involved in emotional processing and that the subthalamic nucleus plays a central in role the human emotional architecture. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  20. An Avian Basal Ganglia-Forebrain Circuit Contributes Differentially to Syllable Versus Sequence Variability of Adult Bengalese Finch Song

    PubMed Central

    Hampton, Cara M.; Sakata, Jon T.; Brainard, Michael S.

    2009-01-01

    Behavioral variability is important for motor skill learning but continues to be present and actively regulated even in well-learned behaviors. In adult songbirds, two types of song variability can persist and are modulated by social context: variability in syllable structure and variability in syllable sequencing. The degree to which the control of both types of adult variability is shared or distinct remains unknown. The output of a basal ganglia-forebrain circuit, LMAN (the lateral magnocellular nucleus of the anterior nidopallium), has been implicated in song variability. For example, in adult zebra finches, neurons in LMAN actively control the variability of syllable structure. It is unclear, however, whether LMAN contributes to variability in adult syllable sequencing because sequence variability in adult zebra finch song is minimal. In contrast, Bengalese finches retain variability in both syllable structure and syllable sequencing into adulthood. We analyzed the effects of LMAN lesions on the variability of syllable structure and sequencing and on the social modulation of these forms of variability in adult Bengalese finches. We found that lesions of LMAN significantly reduced the variability of syllable structure but not of syllable sequencing. We also found that LMAN lesions eliminated the social modulation of the variability of syllable structure but did not detect significant effects on the modulation of sequence variability. These results show that LMAN contributes differentially to syllable versus sequence variability of adult song and suggest that these forms of variability are regulated by distinct neural pathways. PMID:19357331

  1. Lesion of the Centromedian Thalamic Nucleus in MPTP-Treated Monkeys

    PubMed Central

    Lanciego, Jose L.; Rodríguez-Oroz, Maria C.; Blesa, Francisco J.; Alvarez-Erviti, Lydia; Guridi, Jorge; Barroso-Chinea, Pedro; Smith, Yoland; Obeso, Jose A.

    2015-01-01

    The caudal intralaminar nuclei are a major source of glutamatergic afferents to the basal ganglia. Experiments in the 6-hydroxydopamine rat model have shown that the parafascicular nucleus is overactive and its lesion alleviates basal ganglia neurochemical abnormalities associated with dopamine depletion. Accordingly, removal of this excitatory innervation of the basal ganglia could have a beneficial value in the parkinsonian state. To test this hypothesis, unilateral kainate-induced chemical ablation of the centromedian thalamic nucleus (CM) has been performed in MPTP-treated monkeys. Successful lesions restricted to the CM boundaries (n = 2) without spreading over other neighboring thalamic nuclei showed an initial, short-lasting, and mild change in the parkinsonian motor scale but no effect against levodopa-induced dyskinesias. The lack of significant and persistent motor improvement leads us to conclude that unilateral selective lesion of the CM alone cannot be considered as a suitable surgical approach for the treatment of PD or levo-dopa-induced dyskinesias. The role of the caudal intralaminar nuclei in the pathophysiology of movement disorders of basal ganglia origin remains to be clarified. PMID:18175345

  2. Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging

    PubMed Central

    Roussotte, Florence; Soderberg, Lindsay

    2010-01-01

    Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse. PMID:20978945

  3. Optogenetic stimulation in a computational model of the basal ganglia biases action selection and reward prediction error.

    PubMed

    Berthet, Pierre; Lansner, Anders

    2014-01-01

    Optogenetic stimulation of specific types of medium spiny neurons (MSNs) in the striatum has been shown to bias the selection of mice in a two choices task. This shift is dependent on the localisation and on the intensity of the stimulation but also on the recent reward history. We have implemented a way to simulate this increased activity produced by the optical flash in our computational model of the basal ganglia (BG). This abstract model features the direct and indirect pathways commonly described in biology, and a reward prediction pathway (RP). The framework is similar to Actor-Critic methods and to the ventral/dorsal distinction in the striatum. We thus investigated the impact on the selection caused by an added stimulation in each of the three pathways. We were able to reproduce in our model the bias in action selection observed in mice. Our results also showed that biasing the reward prediction is sufficient to create a modification in the action selection. However, we had to increase the percentage of trials with stimulation relative to that in experiments in order to impact the selection. We found that increasing only the reward prediction had a different effect if the stimulation in RP was action dependent (only for a specific action) or not. We further looked at the evolution of the change in the weights depending on the stage of learning within a block. A bias in RP impacts the plasticity differently depending on that stage but also on the outcome. It remains to experimentally test how the dopaminergic neurons are affected by specific stimulations of neurons in the striatum and to relate data to predictions of our model.

  4. A theory about a role of the hyper direct pathway in pattern expression by the basal ganglia.

    PubMed

    Jourdan, Ivan; Barttfeld, Pablo; Zanutto, B Silvano

    2010-01-01

    The Basal Ganglia (BG) are a group of nuclei, in the brain of mammalians and other vertebrates, strongly connected with the cerebral cortex, thalamus and other brain areas. The BG are associated with several brain functions including learning and motor control. When there is cortical activation, there is a strong synchronization between BG and cortex, i.e. when a given task is being executed or in the case of Parkinson disease[1], [2]. If we consider the internal segment of the Globus Pallidus (GPi) there is synchronism between GPi-cortex at frequencies as low as 3Hz to as high as 85Hz [1], [3]. In the other hand, in a delta sleep or in an anesthetized case, a very low frequency correlation is observed (1-10 Hz), but no high frequency correlation between GPi-cortex [1], [2], [3]. It is unknown why this decorrelation happens. But It is agreement that when there is no pattern to select, like in delta sleep or with an anesthetized model, the BG network would maintain the GPi and cortex decorrelated at high frequencies. Many thalamus-BG and thalamus-BG-cortex loops are modulators of the BG activity. Particularly there exists an anatomic thalamus-BG loop, formed by GPi, intralaminar thalamic nuclei (IL) and Subthalamic Nucleus (STN) [4]. Using a computational model, based on an "Integrate and Fire" neural network, we analyzed the IL nucleus as a modulator of the so-called hyper direct pathway. Our results show that, in an anesthetic case, this thalamic path could be relevant to allow a high frequency decorrelated state between the GPi and cortex.

  5. Recent advances in Tourette syndrome research.

    PubMed

    Albin, Roger L; Mink, Jonathan W

    2006-03-01

    Tourette syndrome (TS) is a developmentally regulated neurobehavioral disorder characterized by involuntary, stereotyped, repetitive movements. Recent anatomical and neuroimaging studies have provided evidence for abnormal basal ganglia and dopaminergic function in TS. Basic research on striatal inhibitory mechanisms and dopaminergic function complements the recent neuroimaging and anatomical data. Parallel studies of basal ganglia participation in the normal performance and learning of stereotyped repetitive behaviors or habits has provided additional insight. These lines of research have provided new pieces to the TS puzzle, and their increasing convergence is showing how those pieces can be put together.

  6. The impact of basal ganglia lesions on sensorimotor synchronization, spontaneous motor tempo, and the detection of tempo changes.

    PubMed

    Schwartze, Michael; Keller, Peter E; Patel, Aniruddh D; Kotz, Sonja A

    2011-01-20

    The basal ganglia (BG) are part of extensive subcortico-cortical circuits that are involved in a variety of motor and non-motor cognitive functions. Accumulating evidence suggests that one specific function that engages the BG and associated cortico-striato-thalamo-cortical circuitry is temporal processing, i.e., the mechanisms that underlie the encoding, decoding and evaluation of temporal relations or temporal structure. In the current study we investigated the interplay of two processes that require precise representations of temporal structure, namely the perception of an auditory pacing signal and manual motor production by means of finger tapping in a sensorimotor synchronization task. Patients with focal lesions of the BG and healthy control participants were asked to align finger taps to tone sequences that either did or did not contain a tempo acceleration or tempo deceleration at a predefined position, and to continue tapping at the final tempo after the pacing sequence had ceased. Performance in this adaptive synchronization-continuation paradigm differed between the two groups. Selective damage to the BG affected the abilities to detect tempo changes and to perform attention-dependent error correction, particularly in response to tempo decelerations. An additional assessment of preferred spontaneous, i.e., unpaced but regular, production rates yielded more heterogeneous results in the patient group. Together these findings provide evidence for less efficient processing in the perception and the production of temporal structure in patients with focal BG lesions. The results also support the functional role of the BG system in attention-dependent temporal processing. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. One View of the Current State of Understanding in Basal Ganglia Pathophysiology and What is Needed for the Future

    PubMed Central

    Montgomery, Erwin B.

    2011-01-01

    Deep Brain Stimulation (DBS), arguably, is the most dramatic development in movement disorders since the levodopa for Parkinson’s disease. Yet, its mechanisms of action of DBS are unknown. However, DBS related research already has demonstrated that current concepts of basal ganglia pathophysiology are wrong. Specifically, the notion that over-activity of the globus pallidus interna causes parkinsonism, the basis for the most current theories, is no longer tenable. The development of any new theory will be aided by an understanding of how current theories are wrong and why have these flawed theories persist. Many of the problems of current theories are more matters of inference, assumptions, presumptions, and the accepted level of ambiguity than they are of fact. Consequently, it is imperative that these issues be addressed. Just as the inappropriate use of a tool or method is grounds for criticism, methods of reasoning are tools that can be used inappropriately and should be subject to discussion just as misuse of any other tool. Thorough criticism can provide very important lesions though the process could be mistaken as harsh or personal; neither is the case here. At the least, such analyzes can point to potential pitfalls that could be avoided in the development of new theories. As will be discussed, theories are important for the development of therapies but perhaps most important, for the acceptance of new therapies, as was the case for the recent resurgence of interest in surgical therapies. PMID:24868387

  8. Stimulation sites in the subthalamic nucleus projected onto a mean 3-D atlas of the thalamus and basal ganglia.

    PubMed

    Sarnthein, Johannes; Péus, Dominik; Baumann-Vogel, Heide; Baumann, Christian R; Sürücü, Oguzkan

    2013-09-01

    In patients with severe forms of Parkinson's disease (PD), deep brain stimulation (DBS) commonly targets the subthalamic nucleus (STN). Recently, the mean 3-D Morel-Atlas of the basal ganglia and the thalamus was introduced. It combines information contained in histological data from ten post-mortem brains. We were interested whether the Morel-Atlas is applicable for the visualization of stimulation sites. In a consecutive PD patient series, we documented preoperative MRI planning, intraoperative target adjustment based on electrophysiological and neurological testing, and perioperative CT target reconstruction. The localization of the DBS electrodes and the optimal stimulation sites were projected onto the Morel-Atlas. We included 20 patients (median age 62 years). The active contact had mean coordinates Xlat = ±12.1 mm, Yap = -1.8 mm, Zvert = -3.2 mm. There was a significant difference between the initially planned site and the coordinates of the postoperative active contact site (median 2.2 mm). The stimulation site was, on average, more anterior and more dorsal. The electrode contact used for optimal stimulation was found within the STN of the atlas in 38/40 (95 %) of implantations. The cluster of stimulation sites in individual patients-as deduced from preoperative MR, intraoperative electrophysiology and neurological testing-showed a high degree of congruence with the atlas. The mean 3D Morel Atlas is thus a useful tool for postoperative target visualization. This represents the first clinical evaluation of the recently created atlas.

  9. Oculomotor learning revisited: a model of reinforcement learning in the basal ganglia incorporating an efference copy of motor actions

    PubMed Central

    Fee, Michale S.

    2012-01-01

    In its simplest formulation, reinforcement learning is based on the idea that if an action taken in a particular context is followed by a favorable outcome, then, in the same context, the tendency to produce that action should be strengthened, or reinforced. While reinforcement learning forms the basis of many current theories of basal ganglia (BG) function, these models do not incorporate distinct computational roles for signals that convey context, and those that convey what action an animal takes. Recent experiments in the songbird suggest that vocal-related BG circuitry receives two functionally distinct excitatory inputs. One input is from a cortical region that carries context information about the current “time” in the motor sequence. The other is an efference copy of motor commands from a separate cortical brain region that generates vocal variability during learning. Based on these findings, I propose here a general model of vertebrate BG function that combines context information with a distinct motor efference copy signal. The signals are integrated by a learning rule in which efference copy inputs gate the potentiation of context inputs (but not efference copy inputs) onto medium spiny neurons in response to a rewarded action. The hypothesis is described in terms of a circuit that implements the learning of visually guided saccades. The model makes testable predictions about the anatomical and functional properties of hypothesized context and efference copy inputs to the striatum from both thalamic and cortical sources. PMID:22754501

  10. Oculomotor learning revisited: a model of reinforcement learning in the basal ganglia incorporating an efference copy of motor actions.

    PubMed

    Fee, Michale S

    2012-01-01

    In its simplest formulation, reinforcement learning is based on the idea that if an action taken in a particular context is followed by a favorable outcome, then, in the same context, the tendency to produce that action should be strengthened, or reinforced. While reinforcement learning forms the basis of many current theories of basal ganglia (BG) function, these models do not incorporate distinct computational roles for signals that convey context, and those that convey what action an animal takes. Recent experiments in the songbird suggest that vocal-related BG circuitry receives two functionally distinct excitatory inputs. One input is from a cortical region that carries context information about the current "time" in the motor sequence. The other is an efference copy of motor commands from a separate cortical brain region that generates vocal variability during learning. Based on these findings, I propose here a general model of vertebrate BG function that combines context information with a distinct motor efference copy signal. The signals are integrated by a learning rule in which efference copy inputs gate the potentiation of context inputs (but not efference copy inputs) onto medium spiny neurons in response to a rewarded action. The hypothesis is described in terms of a circuit that implements the learning of visually guided saccades. The model makes testable predictions about the anatomical and functional properties of hypothesized context and efference copy inputs to the striatum from both thalamic and cortical sources.

  11. Deep brain stimulation of the center median-parafascicular complex of the thalamus has efficient anti-parkinsonian action associated with widespread cellular responses in the basal ganglia network in a rat model of Parkinson's disease.

    PubMed

    Jouve, Loréline; Salin, Pascal; Melon, Christophe; Kerkerian-Le Goff, Lydia

    2010-07-21

    The thalamic centromedian-parafascicular (CM/Pf) complex, mainly represented by Pf in rodents, is proposed as an interesting target for the neurosurgical treatment of movement disorders, including Parkinson's disease. In this study, we examined the functional impact of subchronic high-frequency stimulation (HFS) of Pf in the 6-hydroxydopamine-lesioned hemiparkinsonian rat model. Pf-HFS had significant anti-akinetic action, evidenced by alleviation of limb use asymmetry (cylinder test). Whereas this anti-akinetic action was moderate, Pf-HFS totally reversed lateralized neglect (corridor task), suggesting potent action on sensorimotor integration. At the cellular level, Pf-HFS partially reversed the dopamine denervation-induced increase in striatal preproenkephalin A mRNA levels, a marker of the neurons of the indirect pathway, without interfering with the markers of the direct pathway (preprotachykinin and preprodynorphin). Pf-HFS totally reversed the lesion-induced changes in the gene expression of cytochrome oxidase subunit I in the subthalamic nucleus, the globus pallidus, and the substantia nigra pars reticulata, and partially in the entopeduncular nucleus. Unlike HFS of the subthalamic nucleus, Pf-HFS did not induce per se dyskinesias and directly, although partially, alleviated L-3,4-dihydroxyphenylalanine (L-DOPA)-induced forelimb dyskinesia. Conversely, L-DOPA treatment negatively interfered with the anti-parkinsonian effect of Pf-HFS. Altogether, these data show that Pf-DBS, by recruiting a large basal ganglia circuitry, provides moderate to strong anti-parkinsonian benefits that might, however, be affected by L-DOPA. The widespread behavioral and cellular outcomes of Pf-HFS evidenced here demonstrate that CM/Pf is an important node for modulating the pathophysiological functioning of basal ganglia and related disorders.

  12. Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay.

    PubMed

    Floor, E; Wetzel, M G

    1998-01-01

    The dopaminergic phenotype of neurons in human substantia nigra deteriorates during normal aging, and loss of these neurons is prominent in Parkinson's disease. These degenerative processes are hypothesized to involve oxidative stress. To compare oxidative stress in the nigra and related regions, we measured carbonyl modifications of soluble proteins in postmortem samples of substantia nigra, basal ganglia, and prefrontal cortex from neurologically normal subjects, using an improved 2,4-dinitrophenylhydrazine assay. The protein carbonyl content was found to be about twofold higher in substantia nigra pars compacta than in the other regions. To further analyze this oxidative damage, the distribution of carbonyl groups on soluble proteins was determined by western immunoblot analysis. This method revealed that carbonyl content of the major proteins in each region was linearly dependent on molecular weight. This distribution raises the possibility that protein carbonyl content is controlled by a size-dependent mechanism in vivo. Our results suggest that oxidative stress is elevated in human substantia nigra pars compacta in comparison with other regions and that oxidative damage is higher within the dopaminergic neurons. Elevated oxidative damage may contribute to the degeneration of nigral dopaminergic neurons in aging and in Parkinson's disease.

  13. Dynamic stereotypic responses of Basal Ganglia neurons to subthalamic nucleus high-frequency stimulation in the parkinsonian primate.

    PubMed

    Moran, Anan; Stein, Edward; Tischler, Hadass; Belelovsky, Katya; Bar-Gad, Izhar

    2011-01-01

    Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinson's disease (PD); however, its mechanism of action is still unclear. In this study we explored static and dynamic activation patterns in the basal ganglia (BG) during high-frequency macro-stimulation of the STN. Extracellular multi-electrode recordings were performed in primates rendered parkinsonian using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Recordings were preformed simultaneously in the STN and the globus pallidus externus and internus. Single units were recorded preceding and during the stimulation. During the stimulation, STN mean firing rate dropped significantly, while pallidal mean firing rates did not change significantly. The vast majority of neurons across all three nuclei displayed stimulation driven modulations, which were stereotypic within each nucleus but differed across nuclei. The predominant response pattern of STN neurons was somatic inhibition. However, most pallidal neurons demonstrated synaptic activation patterns. A minority of neurons across all nuclei displayed axonal activation. Temporal dynamics were observed in the response to stimulation over the first 10 seconds in the STN and over the first 30 seconds in the pallidum. In both pallidal segments, the synaptic activation response patterns underwent delay and decay of the magnitude of the peak response due to short term synaptic depression. We suggest that during STN macro-stimulation the STN goes through a functional ablation as its upper bound on information transmission drops significantly. This notion is further supported by the evident dissociation between the stimulation driven pre-synaptic STN somatic inhibition and the post-synaptic axonal activation of its downstream targets. Thus, BG output maintains its firing rate while losing the deleterious effect of the STN. This may be a part of the mechanism leading to the beneficial effect of DBS in PD.

  14. Genetics Home Reference: TUBB4A-related leukodystrophy

    MedlinePlus

    ... with atrophy of the basal ganglia and cerebellum (H-ABC). This disorder begins in infancy or early ... early childhood (developmental regression). In addition, individuals with H-ABC have other movement abnormalities, such as involuntary ...

  15. High-frequency stimulation of the globus pallidus interna nucleus modulates GFRα1 gene expression in the basal ganglia.

    PubMed

    Ho, Duncun Xun Kiat; Tan, Yong Chee; Tan, Jiayi; Too, Heng Phon; Ng, Wai Hoe

    2014-04-01

    Deep brain stimulation (DBS) is an established therapy for movement disorders such as Parkinson's disease (PD). Although the efficacy of DBS is clear, its precise molecular mechanism remains unknown. The glial cell line derived factor (GDNF) family of ligands has been shown to confer neuroprotective effects on dopaminergic neurons, and putaminal infusion of GDNF have been investigated in PD patients with promising results. Despite the potential therapeutic role of GDNF in alleviating motor symptoms, there is no data on the effects of electrical stimulation on GDNF-family receptor (GFR) expression in the basal ganglia structures. Here, we report the effects of electrical stimulation on GFRα1 isoforms, particularly GFRα1a and GFRα1b. Wistar rats underwent 2 hours of high frequency stimulation (HFS) at the globus pallidus interna nucleus. A control group was subjected to a similar procedure but without stimulation. The HFS group, sacrificed 24 hours after treatment, had a threefold decrease in mRNA expression level of GFRα1b (p=0.037), but the expression level reverted to normal 72 hours after stimulation. Our preliminary data reveal the acute effects of HFS on splice isoforms of GFRα1, and suggest that HFS may modulate the splice isoforms of GFRα1a and GFRα1b to varying degrees. Going forward, elucidating the interactions between HFS and GFR may shed new insights into the complexity of GDNF signaling in the nervous system and lead to better design of clinical trials using these signaling pathways to halt disease progression in PD and other neurodegenerative diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Herpes Simplex Virus 1 Reactivates from Autonomic Ciliary Ganglia Independently from Sensory Trigeminal Ganglia To Cause Recurrent Ocular Disease

    PubMed Central

    Lee, Sungseok; Ives, Angela M.

    2015-01-01

    ABSTRACT Herpes simplex virus 1 (HSV-1) and HSV-2 establish latency in sensory and autonomic neurons after ocular or genital infection, but their recurrence patterns differ. HSV-1 reactivates from latency to cause recurrent orofacial disease, and while HSV-1 also causes genital lesions, HSV-2 recurs more efficiently in the genital region and rarely causes ocular disease. The mechanisms regulating these anatomical preferences are unclear. To determine whether differences in latent infection and reactivation in autonomic ganglia contribute to differences in HSV-1 and HSV-2 anatomical preferences for recurrent disease, we compared HSV-1 and HSV-2 clinical disease, acute and latent viral loads, and viral gene expression in sensory trigeminal and autonomic superior cervical and ciliary ganglia in a guinea pig ocular infection model. HSV-2 produced more severe acute disease, correlating with higher viral DNA loads in sensory and autonomic ganglia, as well as higher levels of thymidine kinase expression, a marker of productive infection, in autonomic ganglia. HSV-1 reactivated in ciliary ganglia, independently from trigeminal ganglia, to cause more frequent recurrent symptoms, while HSV-2 replicated simultaneously in autonomic and sensory ganglia to cause more persistent disease. While both HSV-1 and HSV-2 expressed the latency-associated transcript (LAT) in the trigeminal and superior cervical ganglia, only HSV-1 expressed LAT in ciliary ganglia, suggesting that HSV-2 is not reactivation competent or does not fully establish latency in ciliary ganglia. Thus, differences in replication and viral gene expression in autonomic ganglia may contribute to differences in HSV-1 and HSV-2 acute and recurrent clinical disease. IMPORTANCE Herpes simplex virus 1 (HSV-1) and HSV-2 establish latent infections, from which the viruses reactivate to cause recurrent disease throughout the life of the host. However, the viruses exhibit different manifestations and frequencies of recurrent

  17. A system-level mathematical model of Basal Ganglia motor-circuit for kinematic planning of arm movements.

    PubMed

    Salimi-Badr, Armin; Ebadzadeh, Mohammad Mehdi; Darlot, Christian

    2018-01-01

    In this paper, a novel system-level mathematical model of the Basal Ganglia (BG) for kinematic planning, is proposed. An arm composed of several segments presents a geometric redundancy. Thus, selecting one trajectory among an infinite number of possible ones requires overcoming redundancy, according to some kinds of optimization. Solving this optimization is assumed to be the function of BG in planning. In the proposed model, first, a mathematical solution of kinematic planning is proposed for movements of a redundant arm in a plane, based on minimizing energy consumption. Next, the function of each part in the model is interpreted as a possible role of a nucleus of BG. Since the kinematic variables are considered as vectors, the proposed model is presented based on the vector calculus. This vector model predicts different neuronal populations in BG which is in accordance with some recent experimental studies. According to the proposed model, the function of the direct pathway is to calculate the necessary rotation of each joint, and the function of the indirect pathway is to control each joint rotation considering the movement of the other joints. In the proposed model, the local feedback loop between Subthalamic Nucleus and Globus Pallidus externus is interpreted as a local memory to store the previous amounts of movements of the other joints, which are utilized by the indirect pathway. In this model, activities of dopaminergic neurons would encode, at short-term, the error between the desired and actual positions of the end-effector. The short-term modulating effect of dopamine on Striatum is also modeled as cross product. The model is simulated to generate the commands of a redundant manipulator. The performance of the model is studied for different reaching movements between 8 points in a plane. Finally, some symptoms of Parkinson's disease such as bradykinesia and akinesia are simulated by modifying the model parameters, inspired by the dopamine depletion

  18. Abuse of Amphetamines and Structural Abnormalities in Brain

    PubMed Central

    Berman, Steven; O’Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D.

    2009-01-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse, and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques that include manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common, and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre-existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain

  19. Abnormal Striatal Dopaminergic Neurotransmission during Rest and Task Production in Spasmodic Dysphonia

    PubMed Central

    Berman, Brian D.; Herscovitch, Peter; Hallett, Mark

    2013-01-01

    Spasmodic dysphonia is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. The pathophysiology of spasmodic dysphonia is thought to involve structural and functional abnormalities in the basal ganglia–thalamo-cortical circuitry; however, neurochemical correlates underpinning these abnormalities as well as their relations to spasmodic dysphonia symptoms remain unknown. We used positron emission tomography with the radioligand [11C]raclopride (RAC) to study striatal dopaminergic neurotransmission at the resting state and during production of symptomatic sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We found that patients, compared to healthy controls, had bilaterally decreased RAC binding potential (BP) to striatal dopamine D2/D3 receptors on average by 29.2%, which was associated with decreased RAC displacement (RAC ΔBP) in the left striatum during symptomatic speaking (group average difference 10.2%), but increased RAC ΔBP in the bilateral striatum during asymptomatic tapping (group average difference 10.1%). Patients with more severe voice symptoms and subclinically longer reaction time to initiate the tapping sequence had greater RAC ΔBP measures, while longer duration of spasmodic dysphonia was associated with a decrease in task-induced RAC ΔBP. Decreased dopaminergic transmission during symptomatic speech production may represent a disorder-specific pathophysiological trait involved in symptom generation, whereas increased dopaminergic function during unaffected task performance may be explained by a compensatory adaptation of the nigrostriatal dopaminergic system possibly due to decreased striatal D2/D3 receptor availability. These changes can be linked to the clinical and subclinical features of spasmodic dysphonia and may represent the neurochemical basis of basal ganglia alterations in this disorder. PMID:24027271

  20. The Frequency and Severity of Magnetic Resonance Imaging Abnormalities in Infants with Mild Neonatal Encephalopathy.

    PubMed

    Walsh, Brian H; Neil, Jeffrey; Morey, JoAnn; Yang, Edward; Silvera, Michelle V; Inder, Terrie E; Ortinau, Cynthia

    2017-08-01

    To assess and contrast the incidence and severity of abnormalities on cerebral magnetic resonance imaging (MRI) between infants with mild, moderate, and severe neonatal encephalopathy who received therapeutic hypothermia. This retrospective cohort studied infants with mild, moderate, and severe neonatal encephalopathy who received therapeutic hypothermia at a single tertiary neonatal intensive care unit between 2013 and 2015. Two neuroradiologists masked to the clinical condition evaluated brain MRIs for cerebral injury after therapeutic hypothermia using the Barkovich classification system. Additional abnormalities not included in this classification system were also noted. The rate, pattern, and severity of abnormalities/injury were compared across the grades of neonatal encephalopathy. Eighty-nine infants received therapeutic hypothermia and met study criteria, 48 with mild neonatal encephalopathy, 35 with moderate neonatal encephalopathy, and 6 with severe neonatal encephalopathy. Forty-eight infants (54%) had an abnormality on MRI. There was no difference in the rate of overall MRI abnormalities by grade of neonatal encephalopathy (mild neonatal encephalopathy 54%, moderate neonatal encephalopathy 54%, and severe neonatal encephalopathy 50%; P= .89). Basal ganglia/thalamic injury was more common in those with severe neonatal encephalopathy (mild neonatal encephalopathy 4%, moderate neonatal encephalopathy 9%, severe neonatal encephalopathy 34%; P = .03). In contrast, watershed injury did not differ between neonatal encephalopathy grades (mild neonatal encephalopathy 36%, moderate neonatal encephalopathy 32%, severe neonatal encephalopathy 50%; P = .3). Mild neonatal encephalopathy is commonly associated with MRI abnormalities after therapeutic hypothermia. The grade of neonatal encephalopathy during the first hours of life may not discriminate adequately between infants with and without cerebral injury noted on MRI after therapeutic hypothermia

  1. Manganese-Induced Atypical Parkinsonism Is Associated with Altered Basal Ganglia Activity and Changes in Tissue Levels of Monoamines in the Rat

    PubMed Central

    Bouabid, Safa; Delaville, Claire; De Deurwaerdère, Philippe; Lakhdar-Ghazal, Nouria; Benazzouz, Abdelhamid

    2014-01-01

    Manganese neurotoxicity is associated with motor and cognitive disturbances known as Manganism. However, the mechanisms underlying these deficits remain unknown. Here we investigated the effects of manganese intoxication on motor and non-motor parkinsonian-like deficits such as locomotor activity, motor coordination, anxiety and “depressive-like” behaviors. Then, we studied the impact of this intoxication on the neuronal activity, the globus pallidus (GP) and subthalamic nucleus (STN). At the end of experiments, post-mortem tissue level of the three monoamines (dopamine, norepinephrine and serotonin) has been determined. The experiments were carried out in adult Sprague-Dawley rats, daily treated with MnCl2 (10 mg/kg/, i.p.) for 5 weeks. We show that manganese progressively reduced locomotor activity as well as motor coordination in parallel with the manifestation of anxiety and “depressive-like” behaviors. Electrophysiological results show that, while majority of GP and STN neurons discharged regularly in controls, manganese increased the number of GP and STN neurons discharging irregularly and/or with bursts. Biochemical results show that manganese significantly decreased tissue levels of norepinephrine and serotonin with increased metabolism of dopamine in the striatum. Our data provide evidence that manganese intoxication is associated with impaired neurotransmission of monoaminergic systems, which is at the origin of changes in basal ganglia neuronal activity and the manifestation of motor and non-motor deficits similar to those observed in atypical Parkinsonism. PMID:24896650

  2. Repetitive transcranial magnetic stimulation for depression after basal ganglia ischaemic stroke: protocol for a multicentre randomised double-blind placebo-controlled trial.

    PubMed

    Tang, Ying; Chen, Aimin; Zhu, Shuzhen; Yang, Li; Zhou, Jiyuan; Pan, Suyue; Shao, Min; Zhao, Lianxu

    2018-02-03

    Studies suggest that repetitive transcranial magnetic stimulation (rTMS) is effective for the treatment of depression and promotes the repair of white matter. This study aims to assess the effectiveness of rTMS in treating depression after basal ganglia ischaemic stroke and to examine whether such effects are related to restoration of white matter integrity. Sixty-six participants will be recruited from Zhujiang Hospital, Nanfang Hospital and Sichuan Bayi Rehabilitation Hospital and randomised in a 1:1 ratio to receive active rTMS treatment or sham rTMS treatment in addition to routine supportive treatments. The data will be collected at 0, 2 and 4 weeks after the commencement of treatment. The primary outcome is the measurement of 24-item Hamilton Depression Rating Scale scores, and the secondary outcomes include diffusion tensor imaging results and the results of neuropsychological tests including the National Institutes of Health Stroke Scale, Activities of Daily Living Scale, Montreal Cognitive Assessment, Clinical Global Impressions scales, Aphasia Battery in Chinese, Social Support Revalued Scale and Medical Coping Modes Questionnaire. This study has been approved by the Ethics Committee of Zhujiang Hospital of Southern Medical University. The findings will be disseminated by publication in a peer-reviewed journal and by presentation at international conferences. NCT03159351. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Good recovery from aphasia is also supported by right basal ganglia: a longitudinal controlled PET study. EJPRM-ESPRM 2008 award winner.

    PubMed

    De Boissezon, X; Marie, N; Castel-Lacanal, E; Marque, P; Bezy, C; Gros, H; Lotterie, J-A; Cardebat, D; Puel, M; Demonet, J-F

    2009-12-01

    It has long been a matter of debate whether recovery from aphasia after left perisylvian lesion is mediated by perilesional left hemispheric regions or by right homologous areas. To investigate the neural substrates of aphasia recovery, a longitudinal study in patients after a left single perisylvian stroke was performed. Thirteen aphasic patients were H2(15)O PET-scanned twice at a one year interval during a word generation task. Patients are divided into two groups according to language performance for the word generation task at PET2. For the Good Recovery (GR) group, patients' performances are indistinguishable from those of normal subjects, while patients from the Poor Recovery (PR) group keep language disorders. Using SPM2, Language-Rest contrast is computed for both groups at both PET stages. Then, Session Effect contrast (TEP2-TEP1>0) is calculated for both groups. For the GR group, the Session Effect contrast shows an increase of activations in the left Postero-Superior Temporal Gyrus PSTG but also in the right thalamus and lenticular nuclei; for PR patients, the right lenticular nucleus activation is more important at PET1 than PET2. The crucial role of the left temporal activation is confirmed and its increase is linked to behavioural recovery. The role of the right basal ganglia to support good recovery from aphasia is a new finding. Their activation may be more task-dependant and related to inhibition of the right frontal cortex.

  4. The Effects of Medium Spiny Neuron Morphologcial Changes on Basal Ganglia Network under External Electric Field: A Computational Modeling Study

    PubMed Central

    Zhang, Xiaohan; Liu, Shenquan; Zhan, Feibiao; Wang, Jing; Jiang, Xiaofang

    2017-01-01

    The damage of dopaminergic neurons that innervate the striatum has been considered to be the proximate cause of Parkinson's disease (PD). In the dopamine-denervated state, the loss of dendritic spines and the decrease of dendritic length may prevent medium spiny neuron (MSN) from receiving too much excitatory stimuli from the cortex, thereby reducing the symptom of Parkinson's disease. However, the reduction in dendritic spine density obtained by different experiments is significantly different. We developed a biological-based network computational model to quantify the effect of dendritic spine loss and dendrites tree degeneration on basal ganglia (BG) signal regulation. Through the introduction of error index (EI), which was used to measure the attenuation of the signal, we explored the amount of dendritic spine loss and dendritic trees degradation required to restore the normal regulatory function of the network, and found that there were two ranges of dendritic spine loss that could reduce EI to normal levels in the case of dopamine at a certain level, this was also true for dendritic trees. However, although these effects were the same, the mechanisms of these two cases were significant difference. Using the method of phase diagram analysis, we gained insight into the mechanism of signal degradation. Furthermore, we explored the role of cortex in MSN morphology changes dopamine depletion-induced and found that proper adjustments to cortical activity do stop the loss in dendritic spines induced by dopamine depleted. These results suggested that modifying cortical drive onto MSN might provide a new idea on clinical therapeutic strategies for Parkinson's disease. PMID:29123477

  5. The Effects of Medium Spiny Neuron Morphologcial Changes on Basal Ganglia Network under External Electric Field: A Computational Modeling Study.

    PubMed

    Zhang, Xiaohan; Liu, Shenquan; Zhan, Feibiao; Wang, Jing; Jiang, Xiaofang

    2017-01-01

    The damage of dopaminergic neurons that innervate the striatum has been considered to be the proximate cause of Parkinson's disease (PD). In the dopamine-denervated state, the loss of dendritic spines and the decrease of dendritic length may prevent medium spiny neuron (MSN) from receiving too much excitatory stimuli from the cortex, thereby reducing the symptom of Parkinson's disease. However, the reduction in dendritic spine density obtained by different experiments is significantly different. We developed a biological-based network computational model to quantify the effect of dendritic spine loss and dendrites tree degeneration on basal ganglia (BG) signal regulation. Through the introduction of error index (EI), which was used to measure the attenuation of the signal, we explored the amount of dendritic spine loss and dendritic trees degradation required to restore the normal regulatory function of the network, and found that there were two ranges of dendritic spine loss that could reduce EI to normal levels in the case of dopamine at a certain level, this was also true for dendritic trees. However, although these effects were the same, the mechanisms of these two cases were significant difference. Using the method of phase diagram analysis, we gained insight into the mechanism of signal degradation. Furthermore, we explored the role of cortex in MSN morphology changes dopamine depletion-induced and found that proper adjustments to cortical activity do stop the loss in dendritic spines induced by dopamine depleted. These results suggested that modifying cortical drive onto MSN might provide a new idea on clinical therapeutic strategies for Parkinson's disease.

  6. Temporal Sequence of Ictal discharges Propagation in the Corticolimbic Basal Ganglia System during Amygdala Kindled Seizures in Freely Moving Rats

    PubMed Central

    Shi, Li-Hong; Luo, Fei; Woodward, Donald J.; McIntyre, Dan C.; Chang, Jing-Yu

    2007-01-01

    We used a multiple channel, single unit recording technique to investigate the neural activity in different corticolimbic and basal ganglia regions in freely moving rats before and during generalized amygdala kindled seizures. Neural activity was recorded simultaneously in the sensorimotor cortex (Ctx), hippocampus, amygdala, substantia nigra pars reticulata (SNr) and the subthalamic nucleus (STN). We observed massive synchronized activity among neurons of different brain regions during seizure episodes. Neurons in the kindled amygdala led other regions in synchronized firing, revealed by time lags of neurons in other regions in crosscorrelogram analysis. While there was no obvious time lag between Ctx and SNr, the STN and hippocampus did lag behind the Ctx and SNr in correlated firing. Activity in the amygdala and SNr contralateral to the kindling stimulation site lagged behind their ipsilateral counterparts. However no time lag was found between the kindling and contralateral sides of Ctx, hippocampus and STN. Our data confirm that the amygdala is an epileptic focus that emits ictal discharges to other brain regions. The observed temporal pattern indicates that ictal discharges from the amygdala arrive first at Ctx and SNr, and then spread to the hippocampus and STN. The simultaneous activation of both sides of the Ctx suggests that the neocortex participates in kindled seizures as a unisonant entity to provoke the clonic motor seizures. Early activation of the SNr (before the STN and hippocampus) points to an important role of the SNr in amygdala kindled seizures and supports the view that different SNr manipulations may be effective ways to control seizures. PMID:17049434

  7. Machine learning classifier using abnormal brain network topological metrics in major depressive disorder.

    PubMed

    Guo, Hao; Cao, Xiaohua; Liu, Zhifen; Li, Haifang; Chen, Junjie; Zhang, Kerang

    2012-12-05

    Resting state functional brain networks have been widely studied in brain disease research. However, it is currently unclear whether abnormal resting state functional brain network metrics can be used with machine learning for the classification of brain diseases. Resting state functional brain networks were constructed for 28 healthy controls and 38 major depressive disorder patients by thresholding partial correlation matrices of 90 regions. Three nodal metrics were calculated using graph theory-based approaches. Nonparametric permutation tests were then used for group comparisons of topological metrics, which were used as classified features in six different algorithms. We used statistical significance as the threshold for selecting features and measured the accuracies of six classifiers with different number of features. A sensitivity analysis method was used to evaluate the importance of different features. The result indicated that some of the regions exhibited significantly abnormal nodal centralities, including the limbic system, basal ganglia, medial temporal, and prefrontal regions. Support vector machine with radial basis kernel function algorithm and neural network algorithm exhibited the highest average accuracy (79.27 and 78.22%, respectively) with 28 features (P<0.05). Correlation analysis between feature importance and the statistical significance of metrics was investigated, and the results revealed a strong positive correlation between them. Overall, the current study demonstrated that major depressive disorder is associated with abnormal functional brain network topological metrics and statistically significant nodal metrics can be successfully used for feature selection in classification algorithms.

  8. Differences in MYB expression and gene abnormalities further confirm that salivary cribriform basal cell tumors and adenoid cystic carcinoma are two distinct tumor entities.

    PubMed

    Tian, Zhen; Li, Lei; Zhang, Chun-Ye; Gu, Ting; Li, Jiang

    2016-10-01

    In practices, some cases of salivary basal cell tumors that consist mainly of cribriform growth pattern are difficult to differentiate from adenoid cystic carcinoma (AdCC). Identification of reliable molecular biomarkers for the differential diagnosis between them is required. Twenty-two cases of cribriform salivary basal cell tumors (at least 10% cribriform pattern present in each tumor) comprising 18 cases of basal cell adenoma (BCA) and four cases of basal cell adenocarcinoma (BcAC) were collected between 1985 and 2008. Twenty cases of cribriform AdCC were retrieved from our archives. MYB protein expression and gene abnormalities were detected in all cases by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analyses, respectively. Neither MYB protein nor split genes were detected in any of the cases of cribriform basal cell tumors, while 55% (11/20) of cases of cribriform AdCC had MYB protein expression. High MYB expression was detected in 81.8% (9/11) cases, while low expression was found in the remaining cases. FISH analysis indicated that nine AdCC tumors with high MYB protein expression were split gene-positive, while MYB gene splitting was not detected in the 11 cases with low or absent MYB protein expression. The molecular changes in AdCC differ from those associated with cribriform basal cell tumors, which further confirms that cribriform basal cell tumors and AdCC are two distinct tumor entities. Simultaneous detection of MYB protein expression and the associated molecular changes could be beneficial in differentiating salivary cribriform basal cell tumors from AdCC. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Action selection performance of a reconfigurable basal ganglia inspired model with Hebbian–Bayesian Go-NoGo connectivity

    PubMed Central

    Berthet, Pierre; Hellgren-Kotaleski, Jeanette; Lansner, Anders

    2012-01-01

    Several studies have shown a strong involvement of the basal ganglia (BG) in action selection and dopamine dependent learning. The dopaminergic signal to striatum, the input stage of the BG, has been commonly described as coding a reward prediction error (RPE), i.e., the difference between the predicted and actual reward. The RPE has been hypothesized to be critical in the modulation of the synaptic plasticity in cortico-striatal synapses in the direct and indirect pathway. We developed an abstract computational model of the BG, with a dual pathway structure functionally corresponding to the direct and indirect pathways, and compared its behavior to biological data as well as other reinforcement learning models. The computations in our model are inspired by Bayesian inference, and the synaptic plasticity changes depend on a three factor Hebbian–Bayesian learning rule based on co-activation of pre- and post-synaptic units and on the value of the RPE. The model builds on a modified Actor-Critic architecture and implements the direct (Go) and the indirect (NoGo) pathway, as well as the reward prediction (RP) system, acting in a complementary fashion. We investigated the performance of the model system when different configurations of the Go, NoGo, and RP system were utilized, e.g., using only the Go, NoGo, or RP system, or combinations of those. Learning performance was investigated in several types of learning paradigms, such as learning-relearning, successive learning, stochastic learning, reversal learning and a two-choice task. The RPE and the activity of the model during learning were similar to monkey electrophysiological and behavioral data. Our results, however, show that there is not a unique best way to configure this BG model to handle well all the learning paradigms tested. We thus suggest that an agent might dynamically configure its action selection mode, possibly depending on task characteristics and also on how much time is available. PMID:23060764

  10. An extended reinforcement learning model of basal ganglia to understand the contributions of serotonin and dopamine in risk-based decision making, reward prediction, and punishment learning

    PubMed Central

    Balasubramani, Pragathi P.; Chakravarthy, V. Srinivasa; Ravindran, Balaraman; Moustafa, Ahmed A.

    2014-01-01

    Although empirical and neural studies show that serotonin (5HT) plays many functional roles in the brain, prior computational models mostly focus on its role in behavioral inhibition. In this study, we present a model of risk based decision making in a modified Reinforcement Learning (RL)-framework. The model depicts the roles of dopamine (DA) and serotonin (5HT) in Basal Ganglia (BG). In this model, the DA signal is represented by the temporal difference error (δ), while the 5HT signal is represented by a parameter (α) that controls risk prediction error. This formulation that accommodates both 5HT and DA reconciles some of the diverse roles of 5HT particularly in connection with the BG system. We apply the model to different experimental paradigms used to study the role of 5HT: (1) Risk-sensitive decision making, where 5HT controls risk assessment, (2) Temporal reward prediction, where 5HT controls time-scale of reward prediction, and (3) Reward/Punishment sensitivity, in which the punishment prediction error depends on 5HT levels. Thus the proposed integrated RL model reconciles several existing theories of 5HT and DA in the BG. PMID:24795614

  11. Abnormal neurofilament inclusions and segregations in dorsal root ganglia of a Charcot-Marie-Tooth type 2E mouse model.

    PubMed

    Zhao, Jian; Brown, Kristy; Liem, Ronald K H

    2017-01-01

    Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy is the most prevalent inherited peripheral neuropathy and is associated with over 90 causative genes. Mutations in neurofilament light polypeptide gene, NEFL cause CMT2E, an axonal form of CMT that results in abnormal structures and/or functions of peripheral axons in spinal cord motor neurons and dorsal root ganglion neurons. We have previously generated and characterized a knock-in mouse model of CMT2E with the N98S mutation in Nefl that presented with multiple inclusions in spinal cord neurons. In this report, we conduct immunofluorescence studies of cultured dorsal root ganglia (DRG) from NeflN98S/+ mice, and show that inclusions found in DRG neurites can occur in embryonic stages. Ultrastructural analyses reveal that the inclusions are disordered neurofilaments packed in high density, segregated from other organelles. Immunochemical studies show decreased NFL protein levels in DRG, cerebellum and spinal cord in NeflN98S/+ mice, and total NFL protein pool is shifted toward the triton-insoluble fraction. Our findings reveal the nature of the inclusions in NeflN98S/+ mice, provide useful information to understand mechanisms of CMT2E disease, and identify DRG from NeflN98S/+ mice as a useful cell line model for therapeutic discoveries.

  12. Use of a Novel High-Resolution Magnetic Resonance Neurography Protocol to Detect Abnormal Dorsal Root Ganglia in Sjögren Patients With Neuropathic Pain

    PubMed Central

    Birnbaum, Julius; Duncan, Trisha; Owoyemi, Kristie; Wang, Kenneth C.; Carrino, John; Chhabra, Avneesh

    2014-01-01

    Abstract The diagnosis and treatment of patients with Sjögren syndrome (SS) with neuropathic pain pose several challenges. Patients with SS may experience unorthodox patterns of burning pain not conforming to a traditional “stocking-and-glove” distribution, which can affect the face, torso, and proximal extremities. This distribution of neuropathic pain may reflect mechanisms targeting the proximal-most element of the peripheral nervous system—the dorsal root ganglia (DRG). Skin biopsy can diagnose such a small-fiber neuropathy and is a surrogate marker of DRG neuronal cell loss. However, SS patients have been reported who have similar patterns of proximal neuropathic pain, despite having normal skin biopsy studies. In such cases, DRGs may be targeted by mechanisms not associated with neuronal cell loss. Therefore, alternative approaches are warranted to help characterize abnormal DRGs in SS patients with proximal neuropathic pain. We performed a systematic review of the literature to define the frequency and spectrum of SS peripheral neuropathies, and to better understand the attribution of SS neuropathic pain to peripheral neuropathies. We found that the frequency of SS neuropathic pain exceeded the prevalence of peripheral neuropathies, and that painful peripheral neuropathies occurred less frequently than neuropathies not always associated with pain. We developed a novel magnetic resonance neurography (MRN) protocol to evaluate DRG abnormalities. Ten SS patients with proximal neuropathic pain were evaluated by this MRN protocol, as well as by punch skin biopsies evaluating for intraepidermal nerve fiber density (IENFD) of unmyelinated nerves. Five patients had radiographic evidence of DRG abnormalities. Patients with MRN DRG abnormalities had increased IENFD of unmyelinated nerves compared to patients without MRN DRG abnormalities (30.2 [interquartile range, 4.4] fibers/mm vs. 11.0 [4.1] fibers/mm, respectively; p = 0.03). Two of these 5 SS patients

  13. Brain abnormalities in high-risk violent offenders and their association with psychopathic traits and criminal recidivism.

    PubMed

    Leutgeb, V; Leitner, M; Wabnegger, A; Klug, D; Scharmüller, W; Zussner, T; Schienle, A

    2015-11-12

    Measures of psychopathy have been proved to be valuable for risk assessment in violent criminals. However, the neuronal basis of psychopathy and its contribution to the prediction of criminal recidivism is still poorly understood. We compared structural imaging data from 40 male high-risk violent offenders and 37 non-delinquent healthy controls via voxel-based morphometry. Psychopathic traits and risk of violence recidivism were correlated with gray matter volume (GMV) of regions of interest previously shown relevant for criminal behavior. Relative to controls, criminals showed less GMV in the prefrontal cortex (PFC) and more GMV in cerebellar regions and basal ganglia structures. Within criminals, we found a negative correlation between prefrontal GMV and psychopathy. Additionally, there was a positive correlation between cerebellar GMV and psychopathy as well as risk of recidivism for violence. Moreover, GMVs of the basal ganglia and supplementary motor area (SMA) were positively correlated with anti-sociality. GMV of the amygdala was negatively correlated with dynamic risk for violence recidivism. In contrast, GMV of (para)limbic areas (orbitofrontal cortex, insula) was positively correlated with anti-sociality and risk of violence recidivism. The current investigation revealed that in violent offenders deviations in GMV of the PFC as well as areas involved in the motor component of impulse control (cerebellum, basal ganglia, SMA) are differentially related to psychopathic traits and the risk of violence recidivism. The results might be valuable for improving existing risk assessment tools. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Cerebral signal intensity abnormalities on T2-weighted MR images in HIV patients with highly active antiretroviral therapy: relationship with clinical parameters and interval changes.

    PubMed

    Hanning, Uta; Husstedt, Ingo W; Niederstadt, Thomas-Ulrich; Evers, Stefan; Heindel, Walter; Kloska, Stephan P

    2011-09-01

    The aim of this study was to assess the relationship between immune state and cerebral signal intensity abnormalities (SIAs) on T2-weighted magnetic resonance images in subjects with human immunodeficiency virus type 1 infection and highly active antiretroviral therapy. Thirty-two subjects underwent a total of 109 magnetic resonance studies. The presence of human immunodeficiency virus-associated neurocognitive disorder, categorized CD4(+) T lymphocyte count, and plasma viral load were assessed for relationship with the severity and interval change of SIAs for different anatomic locations of the brain. Subjects with multifocal patterns of SIAs had CD4(+) cell counts < 200 cells/μL in 66.0%, whereas subjects with diffuse patterns of SIAs had CD4(+) cell counts < 200 cells/μL in only 31.4% (P < .001). Subjects without SIAs in the basal ganglia had CD4(+) cell counts < 200 cells/μL in 37.0%, whereas subjects with minor and moderate SIAs in the basal ganglia had CD4(+) cell counts < 200 cells/μL in 78.3% and 80.0%, respectively (P < .005). The percentage of subjects with CD4(+) cell counts < 200 cells/μL was 85.7% when there were progressive periventricular SIA changes and 45.5% when periventricular SIA changes were stable in follow-up (P < .05). The presence and progression of cerebral SIAs on T2-weighted magnetic resonance images reflecting cerebral infection with human immunodeficiency virus are significantly related to impaired immune state as measured by CD4(+) cell count. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

  15. Dynamical analysis of Parkinsonian state emulated by hybrid Izhikevich neuron models

    NASA Astrophysics Data System (ADS)

    Liu, Chen; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xile; Li, Huiyan; Loparo, Kenneth A.; Fietkiewicz, Chris

    2015-11-01

    Computational models play a significant role in exploring novel theories to complement the findings of physiological experiments. Various computational models have been developed to reveal the mechanisms underlying brain functions. Particularly, in the development of therapies to modulate behavioral and pathological abnormalities, computational models provide the basic foundations to exhibit transitions between physiological and pathological conditions. Considering the significant roles of the intrinsic properties of the globus pallidus and the coupling connections between neurons in determining the firing patterns and the dynamical activities of the basal ganglia neuronal network, we propose a hypothesis that pathological behaviors under the Parkinsonian state may originate from combined effects of intrinsic properties of globus pallidus neurons and synaptic conductances in the whole neuronal network. In order to establish a computational efficient network model, hybrid Izhikevich neuron model is used due to its capacity of capturing the dynamical characteristics of the biological neuronal activities. Detailed analysis of the individual Izhikevich neuron model can assist in understanding the roles of model parameters, which then facilitates the establishment of the basal ganglia-thalamic network model, and contributes to a further exploration of the underlying mechanisms of the Parkinsonian state. Simulation results show that the hybrid Izhikevich neuron model is capable of capturing many of the dynamical properties of the basal ganglia-thalamic neuronal network, such as variations of the firing rates and emergence of synchronous oscillations under the Parkinsonian condition, despite the simplicity of the two-dimensional neuronal model. It may suggest that the computational efficient hybrid Izhikevich neuron model can be used to explore basal ganglia normal and abnormal functions. Especially it provides an efficient way of emulating the large-scale neuron network

  16. Oscillations in sensorimotor cortex in movement disorders: an electrocorticography study.

    PubMed

    Crowell, Andrea L; Ryapolova-Webb, Elena S; Ostrem, Jill L; Galifianakis, Nicholas B; Shimamoto, Shoichi; Lim, Daniel A; Starr, Philip A

    2012-02-01

    Movement disorders of basal ganglia origin may arise from abnormalities in synchronized oscillatory activity in a network that includes the basal ganglia, thalamus and motor cortices. In humans, much has been learned from the study of basal ganglia local field potentials recorded from temporarily externalized deep brain stimulator electrodes. These studies have led to the theory that Parkinson's disease has characteristic alterations in the beta frequency band (13-30 Hz) in the basal ganglia-thalamocortical network. However, different disorders have rarely been compared using recordings in the same structure under the same behavioural conditions, limiting straightforward assessment of current hypotheses. To address this, we utilized subdural electrocorticography to study cortical oscillations in the three most common movement disorders: Parkinson's disease, primary dystonia and essential tremor. We recorded local field potentials from the arm area of primary motor and sensory cortices in 31 subjects using strip electrodes placed temporarily during routine surgery for deep brain stimulator placement. We show that: (i) primary motor cortex broadband gamma power is increased in Parkinson's disease compared with the other conditions, both at rest and during a movement task; (ii) primary motor cortex high beta (20-30 Hz) power is increased in Parkinson's disease during the 'stop' phase of a movement task; (iii) the alpha-beta peaks in the motor and sensory cortical power spectra occur at higher frequencies in Parkinson's disease than in the other two disorders; and (iv) patients with dystonia have impaired movement-related beta band desynchronization in primary motor and sensory cortices. The findings support the emerging hypothesis that disease states reflect abnormalities in synchronized oscillatory activity. This is the first study of sensorimotor cortex local field potentials in the three most common movement disorders.

  17. Basal forebrain neuronal inhibition enables rapid behavioral stopping

    PubMed Central

    Mayse, Jeffrey D.; Nelson, Geoffrey M.; Avila, Irene; Gallagher, Michela; Lin, Shih-Chieh

    2015-01-01

    Cognitive inhibitory control, the ability to rapidly suppress responses inappropriate for the context, is essential for flexible and adaptive behavior. While most studies on inhibitory control have focused on the fronto-basal-ganglia circuit, here we explore a novel hypothesis and show that rapid behavioral stopping is enabled by neuronal inhibition in the basal forebrain (BF). In rats performing the stop signal task, putative noncholinergic BF neurons with phasic bursting responses to the go signal were inhibited nearly completely by the stop signal. The onset of BF neuronal inhibition was tightly coupled with and temporally preceded the latency to stop, the stop signal reaction time. Artificial inhibition of BF activity in the absence of the stop signal was sufficient to reproduce rapid behavioral stopping. These results reveal a novel subcortical mechanism of rapid inhibitory control by the BF, which provides bidirectional control over the speed of response generation and inhibition. PMID:26368943

  18. Basal ganglia dysfunction

    MedlinePlus

    ... disease Metabolic problems Multiple sclerosis (MS) Poisoning with copper, manganese, or other heavy metals Stroke Tumors A ... the brain) Wilson disease (disorder causing too much copper in the body's tissues)

  19. Brain angiogenic gene-expression in congenital heart disease.

    PubMed

    Sánchez, Olga; Ruiz-Romero, Aina; Domínguez, Carmen; Ferrer, Queralt; Ribera, Irene; Rodríguez-Sureda, Víctor; Alijotas, Jaume; Arévalo, Sílvia; Carreras, Elena; Cabero, Lluís; Llurba, Elisa

    2017-12-05

    To analyze potential differences in the expression of antiangiogenic and angiogenic factors and of genes associated with chronic hypoxia in cerebral tissue from euploid fetuses with congenital heart disease (CHD) and control fetuses. Cerebral tissue was obtained from 15 fetuses with CHD and 12 control fetuses undergoing termination of pregnancy. Expression profiles of the antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1), the angiogenic vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF), and genes associated with chronic hypoxia were determined by real-time PCR in tissue from the frontal cortex and from basal ganglia-hypothalamus. sFlt-1 expression was 48% higher in the frontal cortex (p=0.0431) and 72% higher in the basal ganglia-hypothalamus (p=0.0369) of CHD fetuses than controls. VEGF-A expression was 60% higher in the basal ganglia-hypothalamus (p=0.0432) of CHD fetuses. The expression of hypoxia-inducible factor-2α (HIF-2α) in the basal ganglia-hypothalamus was 98% higher in CHD fetuses (p=0.0456). An overall dysregulation of angiogenesis with a net balance towards an antiangiogenic environment was observed in the cerebral tissue from fetuses with CHD, suggesting that these fetuses may have an intrinsic angiogenic impairment that could contribute to impaired brain perfusion and abnormal neurological development later in life. This article is protected by copyright. All rights reserved.

  20. Learning fast accurate movements requires intact frontostriatal circuits

    PubMed Central

    Shabbott, Britne; Ravindran, Roshni; Schumacher, Joseph W.; Wasserman, Paula B.; Marder, Karen S.; Mazzoni, Pietro

    2013-01-01

    The basal ganglia are known to play a crucial role in movement execution, but their importance for motor skill learning remains unclear. Obstacles to our understanding include the lack of a universally accepted definition of motor skill learning (definition confound), and difficulties in distinguishing learning deficits from execution impairments (performance confound). We studied how healthy subjects and subjects with a basal ganglia disorder learn fast accurate reaching movements. We addressed the definition and performance confounds by: (1) focusing on an operationally defined core element of motor skill learning (speed-accuracy learning), and (2) using normal variation in initial performance to separate movement execution impairment from motor learning abnormalities. We measured motor skill learning as performance improvement in a reaching task with a speed-accuracy trade-off. We compared the performance of subjects with Huntington's disease (HD), a neurodegenerative basal ganglia disorder, to that of premanifest carriers of the HD mutation and of control subjects. The initial movements of HD subjects were less skilled (slower and/or less accurate) than those of control subjects. To factor out these differences in initial execution, we modeled the relationship between learning and baseline performance in control subjects. Subjects with HD exhibited a clear learning impairment that was not explained by differences in initial performance. These results support a role for the basal ganglia in both movement execution and motor skill learning. PMID:24312037

  1. Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder.

    PubMed

    Noordermeer, Siri D S; Luman, Marjolein; Greven, Corina U; Veroude, Kim; Faraone, Stephen V; Hartman, Catharina A; Hoekstra, Pieter J; Franke, Barbara; Buitelaar, Jan K; Heslenfeld, Dirk J; Oosterlaan, Jaap

    2017-11-01

    Attention-deficit/hyperactivity disorder (ADHD) is associated with structural abnormalities in total gray matter, basal ganglia, and cerebellum. Findings of structural abnormalities in frontal and temporal lobes, amygdala, and insula are less consistent. Remarkably, the impact of comorbid oppositional defiant disorder (ODD) (comorbidity rates up to 60%) on these neuroanatomical differences is scarcely studied, while ODD (in combination with conduct disorder) has been associated with structural abnormalities of the frontal lobe, amygdala, and insula. The aim of this study was to investigate the effect of comorbid ODD on cerebral volume and cortical thickness in ADHD. Three groups, 16 ± 3.5 years of age (mean ± SD; range 7-29 years), were studied on volumetric and cortical thickness characteristics using structural magnetic resonance imaging (surface-based morphometry): ADHD+ODD (n = 67), ADHD-only (n = 243), and control subjects (n = 233). Analyses included the moderators age, gender, IQ, and scan site. ADHD+ODD and ADHD-only showed volumetric reductions in total gray matter and (mainly) frontal brain areas. Stepwise volumetric reductions (ADHD+ODD < ADHD-only < control subjects) were found for mainly frontal regions, and ADHD+ODD was uniquely associated with reductions in several structures (e.g., the precuneus). In general, findings remained significant after accounting for ADHD symptom severity. There were no group differences in cortical thickness. Exploratory voxelwise analyses showed no group differences. ADHD+ODD and ADHD-only were associated with volumetric reductions in brain areas crucial for attention, (working) memory, and decision-making. Volumetric reductions of frontal lobes were largest in the ADHD+ODD group, possibly underlying observed larger impairments in neurocognitive functions. Previously reported striatal abnormalities in ADHD may be caused by comorbid conduct disorder rather than ODD. Copyright © 2017 Society of Biological Psychiatry

  2. 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

  3. [Mitochondrial leukoencephalopathy of infancy: is it an early expression of Leigh syndrome?].

    PubMed

    Rouco Axpe, I; Garaizar Axpe, C; Labairu Echevarría, M; Sanjurjo Crespo, P; Aldamiz Echevarría, L; Prats Viñas, J M

    2003-06-01

    Leigh syndrome is probably the most frequent metabolic disorder in infancy and childhood. The classic form of the disease is characterized by bilateral lesions of basal ganglia and brainstem. The extensive involvement of white matter, without radiological basal ganglia abnormalities, is an unusual manifestation of the disease. Four patients who presented the disease during the first year of life are described. The four patients presented a stereotyped clinical picture, consisting of regression of already acquired psychomotor abilities and very prominent pyramidal signs. These clinical manifestations and results of neuroimaging studies suggested a primary leukodystrophy. Increased values of lactic and piruvic acids suggested a mitochondrial disorder. Enzymatic studies confirmed a mitochondrial respiratory chain deficiency in two patients, and a pyruvate dehydrogenase complex defect in the remaining two patients. The pathological findings in the latter two sisters were consistent with the characteristic microscopic lesions of Leigh syndrome, but with atypical distribution. Diagnosis of Leigh syndrome must be taken into consideration in infants presenting with a leukodystrophic clinical and radiological pattern, despite the lack of basal ganglia involvement.

  4. Formulaic Language in Parkinson's Disease and Alzheimer's Disease: Complementary Effects of Subcortical and Cortical Dysfunction

    ERIC Educational Resources Information Center

    Van Lancker Sidtis, Diana; Choi, JiHee; Alken, Amy; Sidtis, John J.

    2015-01-01

    Purpose: The production of formulaic expressions (conversational speech formulas, pause fillers, idioms, and other fixed expressions) is excessive in the left hemisphere and deficient in the right hemisphere and in subcortical stroke. Speakers with Alzheimer's disease (AD), having functional basal ganglia, reveal abnormally high proportions of…

  5. Reduced concentrations of N-acetylaspartate (NAA) and the NAA-creatine ratio in the basal ganglia in bipolar disorder: a study using 3-Tesla proton magnetic resonance spectroscopy.

    PubMed

    Frye, Mark A; Thomas, M Albert; Yue, Kenneth; Binesh, Nader; Davanzo, Pablo; Ventura, Joseph; O'Neill, Joseph; Guze, Barry; Curran, John G; Mintz, Jim

    2007-04-15

    The N-acetylaspartate (NAA) peak is prominent in the proton magnetic resonance spectrum and is thought to reflect neuron loss or dysfunction. This study was conducted to explore NAA biochemistry and its clinical correlates in mania. Subjects comprised 16 manic patients and 17 controls who underwent a structured diagnostic interview and (1)H magnetic resonance spectroscopy (MRS) acquisition. STEAM (1)H MRS (TR/TE/TM=2000/20/8 ms) was acquired at 3 Tesla from 2 x 2 x 2 cm(3) voxels in anterior cingulate (AC), right basal ganglia (BG), and left occipital-parietal white matter (OP). Absolute metabolite concentrations and ratios to creatine were calculated using the LC Model. The mean absolute concentrations of NAA and NAA-creatine ratio in the BG were significantly lower in manic subjects than in controls. There was a significant inverse correlation between NAA in the BG and the number of prior hospitalizations for mania. These data suggest BG pathology in mania and that NAA decrements may mark prior manic episode burden. Limitations of this study include small sample size and lack of tissue segmentation. Further study is encouraged to clarify state vs. trait aspects of NAA in bipolar disorder.

  6. [Anomalous systemic arterial supply to normal basal segments of the left lung (Pryce type I)].

    PubMed

    Ryu, Chusei; Sawada, Takahiro; Machino, Ryusuke

    2013-03-01

    Patient 1 was a 54-year-old female diagnosed with anomalous systemic arterial supply to normal basal segments of the left lung discovered as an abnormality on chest X-ray radiography. Patient 2 was a 47-year-old male in whom the disease was diagnosed by close examination of bloody sputum. Division of the abnormal artery and left lower lobectomy were performed in patient 1. Arterial congestion and serpentine distribution were noted in the basal segments of the lung, which was the region perfused by the abnormal artery, on histopathological examination. Arteriosclerotic changes were noted in the vascular wall, but no abnormal vascular wall or alveolar structure was noted in S6, which was not included in theperfused region. Based on the above findings, division of the abnormal artery and left basal segmentectomy were performed in patient 2. Bloody sputum disappeared, and activity of daily living( ADL) were not impaired after surgery.

  7. Cortical-basal ganglionic degeneration.

    PubMed

    Riley, D E; Lang, A E; Lewis, A; Resch, L; Ashby, P; Hornykiewicz, O; Black, S

    1990-08-01

    We report our experience with 15 patients believed to have cortical-basal ganglionic degeneration. The clinical picture is distinctive, comprising features referable to both cortical and basal ganglionic dysfunction. Characteristic manifestations include cortical sensory loss, focal reflex myoclonus, "alien limb" phenomena, apraxia, rigidity and akinesia, a postural-action tremor, limb dystonia, hyperreflexia, and postural instability. The asymmetry of symptoms and signs is often striking. Brain imaging may demonstrate greater abnormalities contralateral to the more affected side. Postmortem studies in 2 patients revealed the characteristic pathologic features of swollen, poorly staining (achromatic) neurons and degeneration of cerebral cortex and substantia nigra. Biochemical analysis of 1 brain showed a severe, diffuse loss of dopamine in the striatum. This condition is more frequent than previously believed, and the diagnosis can be predicted during life on the basis of clinical findings. However, as with other "degenerative" diseases of the nervous system, a definitive diagnosis of cortical-basal ganglionic degeneration requires confirmation by autopsy.

  8. Aberrant Hyperconnectivity in the Motor System at Rest Is Linked to Motor Abnormalities in Schizophrenia Spectrum Disorders.

    PubMed

    Walther, Sebastian; Stegmayer, Katharina; Federspiel, Andrea; Bohlhalter, Stephan; Wiest, Roland; Viher, Petra V

    2017-09-01

    Motor abnormalities are frequently observed in schizophrenia and structural alterations of the motor system have been reported. The association of aberrant motor network function, however, has not been tested. We hypothesized that abnormal functional connectivity would be related to the degree of motor abnormalities in schizophrenia. In 90 subjects (46 patients) we obtained resting stated functional magnetic resonance imaging (fMRI) for 8 minutes 40 seconds at 3T. Participants further completed a motor battery on the scanning day. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity. Principal component analyses of motor behavioral data produced 4 factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). Motor factors were correlated with connectivity values. Schizophrenia was characterized by hyperconnectivity in 3 main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity. Therefore, altered functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Living with idiopathic basal ganglia calcification 3: a qualitative study describing the lives and illness of people diagnosed with a rare neurological disease.

    PubMed

    Takeuchi, Tomiko; Muraoka, Koko; Yamada, Megumi; Nishio, Yuri; Hozumi, Isao

    2016-01-01

    Idiopathic basal ganglia calcification (IBGC) is a rare, intractable disease with unknown etiology. IBGC3 is a familial genetic disease defined by genetic mutations in the major causative gene ( SLC20A2 ). People with IBGC3 experience distress from the uncommon nature of their illness and uncertainty about treatment and prognoses. The present study aimed to describe the lives and illness of people with IBGC3. Participants were recruited from patients aged 20 years or older enrolled in a genetic study, who were diagnosed with IBGC3 and wanted to share their experiences. In-depth semi-structured interviews were conducted with six participants. Interviews were conducted between December 2012 and February 2014, and were recorded and transcribed verbatim. Qualitative data analysis was performed to identify categories and subcategories. Efforts were made to ensure the credibility, transferability, dependability, conformability, and validity of the data. Six thematic categories, 17 subcategories, and 143 codes emerged. The six categories were: (1) Frustration and anxiety with progression of symptoms without a diagnosis; (2) Confusion about diagnosis with an unfamiliar disease; (3) Emotional distress caused by a genetic disease; (4) Passive attitude toward life, being extra careful; (5) Taking charge of life, becoming active and engaged; and (6) Requests for healthcare. The qualitative data analysis indicated a need for genetic counseling, access to disease information, establishment of peer and family support systems, mental health services, and improvement in early intervention and treatment for the disease.

  10. Declarative and Procedural Memory in Danish Speaking Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Lum, Jarrad A. G.; Bleses, Dorthe

    2012-01-01

    It has been proposed that the language problems in specific language impairment (SLI) arise from basal ganglia abnormalities that lead to impairments with procedural and working memory but not declarative memory. In SLI, this profile of memory functioning has been hypothesized to underlie grammatical impairment but leave lexical knowledge…

  11. Structural Changes in the Somatosensory System Correlate with Tic Severity in Gilles de la Tourette Syndrome

    ERIC Educational Resources Information Center

    Thomalla, Gotz; Siebner, Hartwig R.; Jonas, Melanie; Baumer, Tobias; Biermann-Ruben, Katja; Hummel, Friedhelm; Gerloff, Christian; Muller-Vahl, Kirsten; Schnitzler, Alfons; Orth, Michael; Munchau, Alexander

    2009-01-01

    Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. Previous structural MRI studies have identified regional abnormalities in grey matter, especially in the basal ganglia. These findings are consistent with the assumption of alterations in cortico-striato-thalamo-cortical circuits and…

  12. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    PubMed

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  13. Synaptic plasticity and levodopa-induced dyskinesia: electrophysiological and structural abnormalities.

    PubMed

    Picconi, Barbara; De Leonibus, Elvira; Calabresi, Paolo

    2018-02-28

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons located in the midbrain. The gold-standard therapy for PD is the restoration of dopamine (DA) levels through the chronic administration of the DA precursor levodopa (L-DOPA). Although levodopa therapy is the main therapeutic approach for PD, its use is limited by the development of very disabling dyskinetic movements, mainly due to the fluctuation of DA cerebral content. Experimental animal models of PD identified in DA D1/ERK-signaling pathway aberrant activation, occurring in striatal projection neurons, coupled with structural spines abnormalities, the molecular and neuronal basis of L-DOPA-induced dyskinesia (LIDs) occurrence. Different electrophysiological approaches allowed the identification of  the alteration of homeostatic structural and synaptic changes, the neuronal bases of LIDs either in vivo in parkinsonian patients or in vitro in experimental animals. Here, we report the most recent studies showing electrophysiological and morphological evidence of aberrant synaptic plasticity in parkinsonian patients during LIDs in different basal ganglia nuclei and also in cortical transmission, accounting for the complexity of the synaptic changes during dyskinesias. All together, these studies suggest that LIDs are associated with a loss of homeostatic synaptic mechanisms.

  14. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    PubMed Central

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  15. Differential diagnosis of ventriculomegaly and brainstem kinking on fetal MRI.

    PubMed

    Amir, Tali; Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

    2016-01-01

    Fetal ventriculomegaly is a common and frequently leading neuroimaging finding in complex brain malformations. Here we report on pre- and postnatal neuroimaging findings in three fetuses with prenatal ventriculomegaly and brainstem kinking. We aim to identify key neuroimaging features that may allow the prenatal differentiation between diseases associated with fetal ventriculomegaly and brainstem kinking. All pre- and postnatal magnetic resonance imaging (MRI) data were qualitatively evaluated for infra- and supratentorial abnormalities. Data about clinical features and genetic findings were collected from clinical histories. In all three patients, fetal MRI showed ventriculomegaly and brainstem kinking. In two patients, postnatal MRI also showed supratentorial migration abnormalities and eye abnormalities were found. In these children, the diagnosis of α-dystroglycanopathy was genetically confirmed. In the third patient, basal ganglia had an abnormal shape on MRI suggesting a tubulinopathy. The differential diagnosis of prenatal ventriculomegaly and brainstem kinking includes α-dystroglycanopathies, X-linked hydrocephalus due to mutations in L1CAM, and tubulinopathies. The prenatal differentiation between these diseases may be difficult. The presence of ocular abnormalities on prenatal neuroimaging may favor α-dystroglycanopathies, while dysplastic basal ganglia may suggest a tubulinopathy. However, in some patients the final differentiation between these diseases is possible only postnatally. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  16. AP1S2 is mutated in X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome).

    PubMed

    Cacciagli, Pierre; Desvignes, Jean-Pierre; Girard, Nadine; Delepine, Marc; Zelenika, Diana; Lathrop, Mark; Lévy, Nicolas; Ledbetter, David H; Dobyns, William B; Villard, Laurent

    2014-03-01

    MRXS5 or Pettigrew syndrome was described 20 years ago in a four generation family including nine affected individuals presenting with facial dysmorphism, intellectual disability, Dandy-Walker malformation and inconstant choreoathetosis. Four individuals had iron deposition in the basal ganglia seen on MRI or at autopsy. The mutation causing Pettigrew has remained elusive since the initial description of the condition. We report the identification of a mutation in the X-linked AP1S2 gene in the original Pettigrew syndrome family using X-chromosome exome sequencing. We report additional phenotype details for several of the affected individuals, allowing us to further refine the phenotype corresponding to this X-linked intellectual disability syndrome. The AP1S2 c.426+1 G>T mutation segregates with the disease in the Pettigrew syndrome family and results in loss of 46 amino acids in the clathrin adaptor complex small chain domain that spans most of the AP1S2 protein sequence. The mutation reported here in AP1S2 is the first mutation that is not predicted to cause a premature termination of the coding sequence or absence of the AP1S2 protein. Although most of the families affected by a mutation in AP1S2 were initially described as having different disorders assigned to at least three different OMIM numbers (MIM 300629, 300630 and 304340), our analysis of the phenotype shows that they are all the same syndrome with recognition complicated by highly variable expressivity that is seen within as well as between families and is probably not explained by differences in mutation severity.

  17. AP1S2 is mutated in X-linked Dandy–Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome)

    PubMed Central

    Cacciagli, Pierre; Desvignes, Jean-Pierre; Girard, Nadine; Delepine, Marc; Zelenika, Diana; Lathrop, Mark; Lévy, Nicolas; Ledbetter, David H; Dobyns, William B; Villard, Laurent

    2014-01-01

    MRXS5 or Pettigrew syndrome was described 20 years ago in a four generation family including nine affected individuals presenting with facial dysmorphism, intellectual disability, Dandy–Walker malformation and inconstant choreoathetosis. Four individuals had iron deposition in the basal ganglia seen on MRI or at autopsy. The mutation causing Pettigrew has remained elusive since the initial description of the condition. We report the identification of a mutation in the X-linked AP1S2 gene in the original Pettigrew syndrome family using X-chromosome exome sequencing. We report additional phenotype details for several of the affected individuals, allowing us to further refine the phenotype corresponding to this X-linked intellectual disability syndrome. The AP1S2 c.426+1 G>T mutation segregates with the disease in the Pettigrew syndrome family and results in loss of 46 amino acids in the clathrin adaptor complex small chain domain that spans most of the AP1S2 protein sequence. The mutation reported here in AP1S2 is the first mutation that is not predicted to cause a premature termination of the coding sequence or absence of the AP1S2 protein. Although most of the families affected by a mutation in AP1S2 were initially described as having different disorders assigned to at least three different OMIM numbers (MIM 300629, 300630 and 304340), our analysis of the phenotype shows that they are all the same syndrome with recognition complicated by highly variable expressivity that is seen within as well as between families and is probably not explained by differences in mutation severity. PMID:23756445

  18. The oscillatory boundary conditions of different frequency bands in Parkinson's disease.

    PubMed

    Hu, Bing; Shi, Qianqian; Guo, Yu; Diao, Xiyezi; Guo, Heng; Zhang, Jinsong; Yu, Liang; Dai, Hao; Chen, Luonan

    2018-08-14

    Parkinson's disease (PD) is a neurodegenerative disease that is common in the elderly population. The most important pathological change in PD is the degeneration and death of dopaminergic neurons in the substantia nigra of the midbrain, which results in a decrease in the dopamine (DA) content of the striatum. The exact cause of this pathological change is still unknown. Numerous studies have shown that the evolution of PD is associated with abnormal oscillatory activities in the basal ganglia, with different oscillation frequency ranges, such as the typical beta band (13-30 Hz), the alpha band (8-12 Hz), the theta band (4-7 Hz) and the delta band (1-3 Hz). Although some studies have implied that abnormal interactions between the subthalamic nucleus (STN) and globus pallidus (GP) neurons may be a key factor required to induce these oscillations, the relative mechanism is still unclear. The effects of other nerve nuclei in the basal ganglia, such as the striatum, on these oscillations are still unknown. The thalamus and cortex both have close input and output relationships with the basal ganglia, and many previous studies have indicated that they may also exert effects on Parkinson's disease oscillation, but the mechanisms involved are unclear. In this paper, we built a corticothalamic-basal ganglia (CTBG) mean firing-rate model to explore the onset mechanisms of these different oscillation phenomena. We found that, in addition to the STN-GP network, Parkinson's disease oscillations may also be induced by changing the coupling strength and delays in other pathways. Different frequency bands appear in the oscillating region, and various boundary conditions are depicted in parameter diagrams. The onset mechanism is well explained both by the model and by the numerical simulation results. Therefore, this model provides a unifying framework for studying the mechanism of Parkinson's disease oscillations, and we hope that the results obtained in this work can inspire

  19. A Population of Indirect Pathway Striatal Projection Neurons Is Selectively Entrained to Parkinsonian Beta Oscillations

    PubMed Central

    Vinciati, Federica

    2017-01-01

    Classical schemes of basal ganglia organization posit that parkinsonian movement difficulties presenting after striatal dopamine depletion stem from the disproportionate firing rates of spiny projection neurons (SPNs) therein. There remains, however, a pressing need to elucidate striatal SPN firing in the context of the synchronized network oscillations that are abnormally exaggerated in cortical–basal ganglia circuits in parkinsonism. To address this, we recorded unit activities in the dorsal striatum of dopamine-intact and dopamine-depleted rats during two brain states, respectively defined by cortical slow-wave activity (SWA) and activation. Dopamine depletion escalated striatal net output but had contrasting effects on “direct pathway” SPNs (dSPNs) and “indirect pathway” SPNs (iSPNs); their firing rates became imbalanced, and they disparately engaged in network oscillations. Disturbed striatal activity dynamics relating to the slow (∼1 Hz) oscillations prevalent during SWA partly generalized to the exaggerated beta-frequency (15–30 Hz) oscillations arising during cortical activation. In both cases, SPNs exhibited higher incidences of phase-locked firing to ongoing cortical oscillations, and SPN ensembles showed higher levels of rhythmic correlated firing, after dopamine depletion. Importantly, in dopamine-depleted striatum, a widespread population of iSPNs, which often displayed excessive firing rates and aberrant phase-locked firing to cortical beta oscillations, preferentially and excessively synchronized their firing at beta frequencies. Conversely, dSPNs were neither hyperactive nor synchronized to a large extent during cortical activation. These data collectively demonstrate a cell type-selective entrainment of SPN firing to parkinsonian beta oscillations. We conclude that a population of overactive, excessively synchronized iSPNs could orchestrate these pathological rhythms in basal ganglia circuits. SIGNIFICANCE STATEMENT Chronic depletion

  20. Correlation of dopaminergic terminal dysfunction and microstructural abnormalities of the basal ganglia and the olfactory tract in Parkinson's disease.

    PubMed

    Scherfler, Christoph; Esterhammer, Regina; Nocker, Michael; Mahlknecht, Philipp; Stockner, Heike; Warwitz, Boris; Spielberger, Sabine; Pinter, Bernadette; Donnemiller, Eveline; Decristoforo, Clemens; Virgolini, Irene; Schocke, Michael; Poewe, Werner; Seppi, Klaus

    2013-10-01

    Signal abnormalities of the substantia nigra and the olfactory tract detected either by diffusion tensor imaging, including measurements of mean diffusivity, a parameter of brain tissue integrity, and fractional anisotropy, a parameter of neuronal fibre integrity, or transcranial sonography, were recently reported in the early stages of Parkinson's disease. In this study, changes in the nigral and olfactory diffusion tensor signal, as well as nigral echogenicity, were correlated with clinical scales of motor disability, odour function and putaminal dopamine storage capacity measured with 6-[(18)F] fluorolevodopa positron emission tomography in early and advanced stages of Parkinson's disease. Diffusion tensor imaging, transcranial sonography and positron emission tomography were performed on 16 patients with Parkinson's disease (mean disease duration 3.7 ± 3.7 years, Hoehn and Yahr stage 1 to 4) and 14 age-matched healthy control subjects. Odour function was measured by the standardized Sniffin' Sticks Test. Mean putaminal 6-[(18)F] fluorolevodopa influx constant, mean nigral echogenicity, mean diffusivity and fractional anisotropy values of the substantia nigra and the olfactory tract were identified by region of interest analysis. When compared with the healthy control group, the Parkinson's disease group showed significant signal changes in the caudate and putamen by 6-[(18)F] fluorolevodopa positron emission tomography, in the substantia nigra by transcranial sonography, mean diffusivity and fractional anisotropy (P < 0.001, P < 0.01, P < 0.05, respectively) and in the olfactory tract by mean diffusivity (P < 0.05). Regional mean diffusivity values of the substantia nigra and the olfactory tract correlated significantly with putaminal 6-[(18)F] fluorolevodopa uptake (r = -0.52, P < 0.05 and r = -0.71, P < 0.01). Significant correlations were also found between nigral mean diffusivity values and the Unified Parkinson's Disease Rating Scale motor score (r = -0

  1. Endogenous neurotrophin-3 promotes neuronal sprouting from dorsal root ganglia.

    PubMed

    Wang, Xu-Yang; Gu, Pei-Yuan; Chen, Shi-Wen; Gao, Wen-Wei; Tian, Heng-Li; Lu, Xiang-He; Zheng, Wei-Ming; Zhuge, Qi-Chuan; Hu, Wei-Xing

    2015-11-01

    In the present study, we investigated the role of endogenous neurotrophin-3 in nerve terminal sprouting 2 months after spinal cord dorsal root rhizotomy. The left L1-5 and L7-S2 dorsal root ganglia in adult cats were exposed and removed, preserving the L6 dorsal root ganglia. Neurotrophin-3 was mainly expressed in large neurons in the dorsal root ganglia and in some neurons in spinal lamina II. Two months after rhizotomy, the number of neurotrophin-3-positive neurons in the spared dorsal root ganglia and the density of neurite sprouts emerging from these ganglia were increased. Intraperitoneal injection of an antibody against neurotrophin-3 decreased the density of neurite sprouts. These findings suggest that endogenous neurotrophin-3 is involved in spinal cord plasticity and regeneration, and that it promotes axonal sprouting from the dorsal root ganglia after spinal cord dorsal root rhizotomy.

  2. Parkinson's disease as a system-level disorder.

    PubMed

    Caligiore, Daniele; Helmich, Rick C; Hallett, Mark; Moustafa, Ahmed A; Timmermann, Lars; Toni, Ivan; Baldassarre, Gianluca

    2016-01-01

    Traditionally, the basal ganglia have been considered the main brain region implicated in Parkinson's disease. This single area perspective gives a restricted clinical picture and limits therapeutic approaches because it ignores the influence of altered interactions between the basal ganglia and other cerebral components on Parkinsonian symptoms. In particular, the basal ganglia work closely in concert with cortex and cerebellum to support motor and cognitive functions. This article proposes a theoretical framework for understanding Parkinson's disease as caused by the dysfunction of the entire basal ganglia-cortex-cerebellum system rather than by the basal ganglia in isolation. In particular, building on recent evidence, we propose that the three key symptoms of tremor, freezing, and impairments in action sequencing may be explained by considering partially overlapping neural circuits including basal ganglia, cortical and cerebellar areas. Studying the involvement of this system in Parkinson's disease is a crucial step for devising innovative therapeutic approaches targeting it rather than only the basal ganglia. Possible future therapies based on this different view of the disease are discussed.

  3. An essential role of the basal body protein SAS-6 in Plasmodium male gamete development and malaria transmission

    PubMed Central

    Marques, Sara R; Ramakrishnan, Chandra; Carzaniga, Raffaella; Blagborough, Andrew M; Delves, Michael J; Talman, Arthur M; Sinden, Robert E

    2015-01-01

    Gametocytes are the sole Plasmodium parasite stages that infect mosquitoes; therefore development of functional gametes is required for malaria transmission. Flagellum assembly of the Plasmodium male gamete differs from that of most other eukaryotes in that it is intracytoplasmic but retains a key conserved feature: axonemes assemble from basal bodies. The centriole/basal body protein SAS-6 normally regulates assembly and duplication of these organelles and its depletion causes severe flagellar/ciliary abnormalities in a diverse array of eukaryotes. Since basal body and flagellum assembly are intimately coupled to male gamete development in Plasmodium, we hypothesized that SAS-6 disruption may cause gametogenesis defects and perturb transmission. We show that Plasmodium berghei sas6 knockouts display severely abnormal male gametogenesis presenting reduced basal body numbers, axonemal assembly defects and abnormal nuclear allocation. The defects in gametogenesis reduce fertilization and render Pbsas6 knockouts less infectious to mosquitoes. Additionally, we show that lack of Pbsas6 blocks transmission from mosquito to vertebrate host, revealing an additional yet undefined role in ookinete to sporulating oocysts transition. These findings underscore the vulnerability of the basal body/SAS-6 to malaria transmission blocking interventions. PMID:25154861

  4. MR Anatomy of Deep Brain Nuclei with Special Reference to Specific Diseases and Deep Brain Stimulation Localization

    PubMed Central

    Telford, Ryan; Vattoth, Surjith

    2014-01-01

    Summary Diseases affecting the basal ganglia and deep brain structures vary widely in etiology and include metabolic, infectious, ischemic, and neurodegenerative conditions. Some neurologic diseases, such as Wernicke encephalopathy or pseudohypoparathyroidism, require specific treatments, which if unrecognized could lead to further complications. Other pathologies, such as hypertrophic olivary degeneration, if not properly diagnosed may be mistaken for a primary medullary neoplasm and create unnecessary concern. The deep brain structures are complex and can be difficult to distinguish on routine imaging. It is imperative that radiologists first understand the intrinsic anatomic relationships between the different basal ganglia nuclei and deep brain structures with magnetic resonance (MR) imaging. It is important to understand the "normal" MR signal characteristics, locations, and appearances of these structures. This is essential to recognizing diseases affecting the basal ganglia and deep brain structures, especially since most of these diseases result in symmetrical, and therefore less noticeable, abnormalities. It is also crucial that neurosurgeons correctly identify the deep brain nuclei presurgically for positioning deep brain stimulator leads, the most important being the subthalamic nucleus for Parkinson syndromes and the thalamic ventral intermediate nucleus for essential tremor. Radiologists will be able to better assist clinicians in diagnosis and treatment once they are able to accurately localize specific deep brain structures. PMID:24571832

  5. Pallidostriatal Projections Promote β Oscillations in a Dopamine-Depleted Biophysical Network Model

    PubMed Central

    Corbit, Victoria L.; Whalen, Timothy C.; Zitelli, Kevin T.; Crilly, Stephanie Y.; Rubin, Jonathan E.

    2016-01-01

    propagating abnormal circuit activity to striatum, which in turn projects to downstream basal ganglia structures. These findings warrant further exploration of GPe as a target for interventions for Parkinson's disease. PMID:27194335

  6. The Multiple Correspondence Analysis Method and Brain Functional Connectivity: Its Application to the Study of the Non-linear Relationships of Motor Cortex and Basal Ganglia.

    PubMed

    Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Rodriguez, Manuel

    2017-01-01

    The complexity of basal ganglia (BG) interactions is often condensed into simple models mainly based on animal data and that present BG in closed-loop cortico-subcortical circuits of excitatory/inhibitory pathways which analyze the incoming cortical data and return the processed information to the cortex. This study was aimed at identifying functional relationships in the BG motor-loop of 24 healthy-subjects who provided written, informed consent and whose BOLD-activity was recorded by MRI methods. The analysis of the functional interaction between these centers by correlation techniques and multiple linear regression showed non-linear relationships which cannot be suitably addressed with these methods. The multiple correspondence analysis (MCA), an unsupervised multivariable procedure which can identify non-linear interactions, was used to study the functional connectivity of BG when subjects were at rest. Linear methods showed different functional interactions expected according to current BG models. MCA showed additional functional interactions which were not evident when using lineal methods. Seven functional configurations of BG were identified with MCA, two involving the primary motor and somatosensory cortex, one involving the deepest BG (external-internal globus pallidum, subthalamic nucleus and substantia nigral), one with the input-output BG centers (putamen and motor thalamus), two linking the input-output centers with other BG (external pallidum and subthalamic nucleus), and one linking the external pallidum and the substantia nigral. The results provide evidence that the non-linear MCA and linear methods are complementary and should be best used in conjunction to more fully understand the nature of functional connectivity of brain centers.

  7. [Walking abnormalities in children].

    PubMed

    Segawa, Masaya

    2010-11-01

    Walking is a spontaneous movement termed locomotion that is promoted by activation of antigravity muscles by serotonergic (5HT) neurons. Development of antigravity activity follows 3 developmental epochs of the sleep-wake (S-W) cycle and is modulated by particular 5HT neurons in each epoch. Activation of antigravity activities occurs in the first epoch (around the age of 3 to 4 months) as restriction of atonia in rapid eye movement (REM) stage and development of circadian S-W cycle. These activities strengthen in the second epoch, with modulation of day-time sleep and induction of crawling around the age of 8 months and induction of walking by 1 year. Around the age of 1 year 6 months, absence of guarded walking and interlimb cordination is observed along with modulation of day-time sleep to once in the afternoon. Bipedal walking in upright position occurs in the third epoch, with development of a biphasic S-W cycle by the age of 4-5 years. Patients with infantile autism (IA), Rett syndrome (RTT), or Tourette syndrome (TS) show failure in the development of the first, second, or third epoch, respectively. Patients with IA fail to develop interlimb coordination; those with RTT, crawling and walking; and those with TS, walking in upright posture. Basic pathophysiology underlying these condition is failure in restricting atonia in REM stage; this induces dysfunction of the pedunculopontine nucleus and consequently dys- or hypofunction of the dopamine (DA) neurons. DA hypofunction in the developing brain, associated with compensatory upward regulation of the DA receptors causes psychobehavioral disorders in infancy (IA), failure in synaptogenesis in the frontal cortex and functional development of the motor and associate cortexes in late infancy through the basal ganglia (RTT), and failure in functional development of the prefrontal cortex through the basal ganglia (TS). Further, locomotion failure in early childhood causes failure in development of functional

  8. Intercellular communication in sensory ganglia by purinergic receptors and gap junctions: implications for chronic pain.

    PubMed

    Hanani, Menachem

    2012-12-03

    Peripheral injury can cause abnormal activity in sensory neurons, which is a major factor in chronic pain. Recent work has shown that injury induces major changes not only in sensory neurons but also in the main type of glial cells in sensory ganglia-satellite glial cells (SGCs), and that interactions between sensory neurons and SGCs contribute to neuronal activity in pain models. The main functional changes observed in SGCs after injury are an increased gap junction-mediated coupling among these cells, and augmented sensitivity to ATP. There is evidence that the augmented gap junctions contribute to neuronal hyperexcitability in pain models, but the mechanism underlying this effect is not known. The changes in SGCs described above have been found following a wide range of injuries (both axotomy and inflammation) in somatic, orofacial and visceral regions, and therefore appear to be a general feature in chronic pain. We have found that in cultures of sensory ganglia calcium signals can spread from an SGC to neighboring cells by calcium waves, which are mediated by gap junctions and ATP acting on purinergic P2 receptors. A model is proposed to explain how augmented gap junctions and greater sensitivity to ATP can combine to produce enhanced calcium waves, which can lead to neuronal excitation. Thus this simple scheme can account for several major changes in sensory ganglia that are common to a great variety of pain models. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. SPECT brain perfusion abnormalities in mild or moderate traumatic brain injury.

    PubMed

    Abdel-Dayem, H M; Abu-Judeh, H; Kumar, M; Atay, S; Naddaf, S; El-Zeftawy, H; Luo, J Q

    1998-05-01

    The purpose of this atlas is to present a review of the literature showing the advantages of SPECT brain perfusion imaging (BPI) in mild or moderate traumatic brain injury (TBI) over other morphologic imaging modalities such as x-ray CT or MRI. The authors also present the technical recommendations for SPECT brain perfusion currently practiced at their center. For the radiopharmaceutical of choice, a comparison between early and delayed images using Tc-99m HMPAO and Tc-99m ECD showed that Tc-99m HMPAO is more stable in the brain with no washout over time. Therefore, the authors feel that Tc-99m HMPAO is preferable to Tc-99m ECD. Recommendations regarding standardizing intravenous injection, the acquisition, processing parameters, and interpretation of scans using a ten grade color scale, and use of the cerebellum as the reference organ are presented. SPECT images of 228 patients (age range, 11 to 88; mean, 40.8 years) with mild or moderate TBI and no significant medical history that interfered with the results of the SPECT BP were reviewed. The etiology of the trauma was in the following order of frequency: motor vehicle accidents (45%) followed by blow to the head (36%) and a fall (19%). Frequency of the symptoms was headache (60.9%), memory problems (27.6%), dizziness (26.7%), and sleep disorders (8.7%). Comparison between patients imaged early (<3 months) versus those imaged delayed (>3 months) from the time of the accident, showed that early imaging detected more lesions (4.2 abnormal lesions per study compared to 2.7 in those imaged more than 3 months after the accident). Of 41 patients who had mild traumatic injury without loss of consciousness and had normal CT, 28 studies were abnormal. Focal areas of hypoperfusion were seen in 77% (176 patients, 612 lesions) of the group of 228 patients. The sites of abnormalities were in the following order: basal ganglia and thalami, 55.2%, frontal lobes, 23.8%, temporal lobes, 13%, parietal, 3.7%, insular and occipital

  10. The temptation of suicide: striatal gray matter, discounting of delayed rewards, and suicide attempts in late-life depression

    PubMed Central

    Dombrovski, Alexandre Y.; Siegle, Greg J.; Szanto, Katalin; Clark, Luke; Reynolds, Charles F.; Aizenstein, Howard

    2012-01-01

    Background Converging evidence implicates basal ganglia alterations in impulsivity and suicidal behavior. For example, D2/D3 agonists and subthalamic nucleus stimulation in Parkinson’s disease trigger impulse control disorders and possibly suicidal behavior. Further, suicidal behavior has been associated with structural basal ganglia abnormalities. Finally, low-lethality, unplanned suicide attempts are associated with increased discounting of delayed rewards, a behavior dependent upon the striatum. Thus, we tested whether, in late-life depression, changes in the basal ganglia were associated with suicide attempts and with increased delay discounting. Methods Fifty-two persons aged ≥60 underwent extensive clinical and cognitive characterization: 33 with major depression (13 suicide attempters [SA], 20 non-suicidal depressed elderly), and 19 non-depressed controls. Participants had high-resolution T1-weighted MPRAGE MRI scans. Basal ganglia gray matter voxel counts were estimated using atlas-based segmentation, with a highly-deformable automated algorithm. Discounting of delayed rewards was assessed using the Monetary Choice Questionnaire, and delay aversion with the Cambridge Gamble Task. Results SA had lower putamen but not caudate or pallidum gray matter voxel counts, compared to the control groups. This difference persisted after accounting for substance use disorders and possible brain injury from suicide attempts. SA with lower putamen gray matter voxel counts displayed higher delay discounting on the MCQ, but not delay aversion on the CGT. Secondary analyses revealed that SA had lower voxel counts in associative and possibly ventral, but not sensorimotor striatum. Conclusions Our findings, while limited by small sample size and case-control design, suggest that striatal lesions could contribute to suicidal behavior by increasing impulsivity. PMID:21999930

  11. The temptation of suicide: striatal gray matter, discounting of delayed rewards, and suicide attempts in late-life depression.

    PubMed

    Dombrovski, A Y; Siegle, G J; Szanto, K; Clark, L; Reynolds, C F; Aizenstein, H

    2012-06-01

    Converging evidence implicates basal ganglia alterations in impulsivity and suicidal behavior. For example, D2/D3 agonists and subthalamic nucleus stimulation in Parkinson's disease (PD) trigger impulse control disorders and possibly suicidal behavior. Furthermore, suicidal behavior has been associated with structural basal ganglia abnormalities. Finally, low-lethality, unplanned suicide attempts are associated with increased discounting of delayed rewards, a behavior dependent upon the striatum. Thus, we tested whether, in late-life depression, changes in the basal ganglia were associated with suicide attempts and with increased delay discounting. Fifty-two persons aged ≥ 60 years underwent extensive clinical and cognitive characterization: 33 with major depression [13 suicide attempters (SA), 20 non-suicidal depressed elderly] and 19 non-depressed controls. Participants had high-resolution T1-weighted magnetization prepared rapid acquisition gradient-echo (MPRAGE) magnetic resonance imaging (MRI) scans. Basal ganglia gray matter voxel counts were estimated using atlas-based segmentation, with a highly deformable automated algorithm. Discounting of delayed rewards was assessed using the Monetary Choice Questionnaire (MCQ) and delay aversion with the Cambridge Gamble Task (CGT). SA had lower putamen but not caudate or pallidum gray matter voxel counts, compared to the control groups. This difference persisted after accounting for substance use disorders and possible brain injury from suicide attempts. SA with lower putamen gray matter voxel counts displayed higher delay discounting but not delay aversion. Secondary analyses revealed that SA had lower voxel counts in associative and ventral but not sensorimotor striatum. Our findings, although limited by small sample size and the case-control design, suggest that striatal lesions could contribute to suicidal behavior by increasing impulsivity.

  12. Speeded processing of grammar and tool knowledge in Tourette’s syndrome

    PubMed Central

    Walenski, Matthew; Mostofsky, Stewart H.; Ullman, Michael T.

    2007-01-01

    Tourette’s syndrome (TS) is a developmental disorder characterized by motor and verbal tics. The tics, which are fast and involuntary, result from frontal/basal-ganglia abnormalities that lead to unsuppressed behaviors. Language has not been carefully examined in TS. We tested the processing of two basic aspects of language: idiosyncratic and rule-governed linguistic knowledge. Evidence suggests that idiosyncratic knowledge (e.g., in irregular past-tense formation; bring-brought) is stored in a mental lexicon that depends on the temporal-lobe-based declarative memory system that also underlies conceptual knowledge. In contrast, evidence suggests that rule-governed combination (e.g., in regular past-tenses; walk + -ed) takes place in a mental grammar that relies on the frontal/basal-ganglia based procedural memory system, which also underlies motor skills such as how to use a hammer. We found that TS children were significantly faster than typically-developing control children at producing rule-governed past-tenses (slip-slipped, plim-plimmed, bring-bringed) but not irregular and other unpredictable past-tenses (bring-brought, splim-splam). They were also faster than controls at naming pictures of manipulated (hammer) but not non-manipulated (elephant) items. These data were not explained by a wide range of potentially confounding subject- and item-level factors. The results suggest that the processing of procedurally-based knowledge, both of grammar and of manipulated objects, is particularly speeded in TS. The frontal/basal-ganglia abnormalities may thus lead not only to tics, but to a wider range of rapid behaviors, including in the cognitive processing of rule-governed forms in language and other types of procedural knowledge. PMID:17493643

  13. Parkinson’s disease as a system-level disorder

    PubMed Central

    Caligiore, Daniele; Helmich, Rick C; Hallett, Mark; Moustafa, Ahmed A; Timmermann, Lars; Toni, Ivan; Baldassarre, Gianluca

    2016-01-01

    Traditionally, the basal ganglia have been considered the main brain region implicated in Parkinson’s disease. This single area perspective gives a restricted clinical picture and limits therapeutic approaches because it ignores the influence of altered interactions between the basal ganglia and other cerebral components on Parkinsonian symptoms. In particular, the basal ganglia work closely in concert with cortex and cerebellum to support motor and cognitive functions. This article proposes a theoretical framework for understanding Parkinson’s disease as caused by the dysfunction of the entire basal ganglia–cortex–cerebellum system rather than by the basal ganglia in isolation. In particular, building on recent evidence, we propose that the three key symptoms of tremor, freezing, and impairments in action sequencing may be explained by considering partially overlapping neural circuits including basal ganglia, cortical and cerebellar areas. Studying the involvement of this system in Parkinson’s disease is a crucial step for devising innovative therapeutic approaches targeting it rather than only the basal ganglia. Possible future therapies based on this different view of the disease are discussed. PMID:28725705

  14. Endogenous angiotensinergic system in neurons of rat and human trigeminal ganglia

    PubMed Central

    Imboden, Hans; Patil, Jaspal; Nussberger, Juerg; Nicoud, Françoise; Hess, Benno; Ahmed, Nermin; Schaffner, Thomas; Wellner, Maren; Müller, Dominik; Inagami, Tadashi; Senbonmatsu, Takaaki; Pavel, Jaroslav; Saavedra, Juan M.

    2009-01-01

    To clarify the role of Angiotensin II (Ang II) in the sensory system and especially in the trigeminal ganglia, we studied the expression of angiotensinogen (Ang-N)-, renin-, angiotensin converting enzyme (ACE)- and cathepsin D-mRNA, and the presence of Ang II and substance P in the rat and human trigeminal ganglia. The rat trigeminal ganglia expressed substantial amounts of Ang-N- and ACE mRNA as determined by quantitative real time PCR. Renin mRNA was untraceable in rat samples. Cathepsin D was detected in the rat trigeminal ganglia indicating the possibility of existence of pathways alternative to renin for Ang I formation. In situ hybridization in rat trigeminal ganglia revealed expression of Ang-N mRNA in the cytoplasm of numerous neurons. By using immunocytochemistry, a number of neurons and their processes in both the rat and human trigeminal ganglia were stained for Ang II. Post in situ hybridization immunocytochemistry reveals that in the rat trigeminal ganglia some, but not all Ang-N mRNA-positive neurons marked for Ang II. In some neurons Substance P was found colocalized with Ang II. Angiotensins from rat trigeminal ganglia were quantitated by radioimmunoassay with and without prior separation by high performance liquid chromatography. Immunoreactive angiotensin II (ir-Ang II) was consistently present and the sum of true Ang II (1-8) octapeptide and its specifically measured metabolites were found to account for it. Radioimmunological and immunocytochemical evidence of ir-Ang II in neuronal tissue is compatible with Ang II as a neurotransmitter. In conclusion, these results suggest that Ang II could be produced locally in the neurons of rat trigeminal ganglia. The localization and colocalization of neuronal Ang II with Substance P in the trigeminal ganglia neurons may be the basis for a participation and function of Ang II in the regulation of nociception and migraine pathology. PMID:19323983

  15. Cognitive slowing in Parkinson disease is accompanied by hypofunctioning of the striatum.

    PubMed

    Sawamoto, N; Honda, M; Hanakawa, T; Aso, T; Inoue, M; Toyoda, H; Ishizu, K; Fukuyama, H; Shibasaki, H

    2007-03-27

    To investigate whether cognitive slowing in Parkinson disease (PD) reflects disruption of the basal ganglia or dysfunction of the frontal lobe by excluding an influence of abnormal brain activity due to motor deficits. We measured neuronal activity during a verbal mental-operation task with H(2)(15)O PET. This task enabled us to evaluate brain activity change associated with an increase in the cognitive speed without an influence on motor deficits. As the speed of the verbal mental-operation task increased, healthy controls exhibited proportional increase in activities in the anterior striatum and medial premotor cortex, suggesting the involvement of the corticobasal ganglia circuit in normal performance of the task. By contrast, patients with PD lacked an increase in the striatal activity, whereas the medial premotor cortex showed a proportional increase. Although the present study chose a liberal threshold and needs subsequent confirmation, the findings suggest that striatal disruption resulting in abnormal processing in the corticobasal ganglia circuit may contribute to cognitive slowing in Parkinson disease, as is the case in motor slowing.

  16. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number.

    PubMed

    Lyons, Jonathan J; Yu, Xiaomin; Hughes, Jason D; Le, Quang T; Jamil, Ali; Bai, Yun; Ho, Nancy; Zhao, Ming; Liu, Yihui; O'Connell, Michael P; Trivedi, Neil N; Nelson, Celeste; DiMaggio, Thomas; Jones, Nina; Matthews, Helen; Lewis, Katie L; Oler, Andrew J; Carlson, Ryan J; Arkwright, Peter D; Hong, Celine; Agama, Sherene; Wilson, Todd M; Tucker, Sofie; Zhang, Yu; McElwee, Joshua J; Pao, Maryland; Glover, Sarah C; Rothenberg, Marc E; Hohman, Robert J; Stone, Kelly D; Caughey, George H; Heller, Theo; Metcalfe, Dean D; Biesecker, Leslie G; Schwartz, Lawrence B; Milner, Joshua D

    2016-12-01

    Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia.

  17. Differences in Signal Intensity and Enhancement on MR Images of the Perivascular Spaces in the Basal Ganglia versus Those in White Matter.

    PubMed

    Naganawa, Shinji; Nakane, Toshiki; Kawai, Hisashi; Taoka, Toshiaki

    2018-01-18

    To elucidate differences between the perivascular space (PVS) in the basal ganglia (BG) versus that found in white matter (WM) using heavily T 2 -weighted FLAIR (hT 2 -FL) in terms of 1) signal intensity on non-contrast enhanced images, and 2) the degree of contrast enhancement by intravenous single dose administration of gadolinium based contrast agent (IV-SD-GBCA). Eight healthy men and 13 patients with suspected endolymphatic hydrops were included. No subjects had renal insufficiency. All subjects received IV-SD-GBCA. MR cisternography (MRC) and hT 2 -FL images were obtained prior to and 4 h after IV-SD-GBCA. The signal intensity of the PVS in the BG, subinsular WM, and the cerebrospinal fluid (CSF) in Ambient cistern (CSF AC ) and CSF in Sylvian fissure (CSF Syl ) was measured as well as that of the thalamus. The signal intensity ratio (SIR) was calculated by dividing the intensity by that of the thalamus. We used 5% as a threshold to determine the significance of the statistical test. In the pre-contrast scan, the SIR of the PVS in WM (Mean ± standard deviation, 1.83 ± 0.46) was significantly higher than that of the PVS in the BG (1.05 ± 0.154), CSF Syl (1.03 ± 0.15) and the CSF AC (0.97 ± 0.29). There was no significant difference between the SIR of the PVS in the BG compared to the CSF AC and CSF Syl . For the evaluation of the contrast enhancement effect, significant enhancement was observed in the PVS in the BG, the CSF AC and the CSF Syl compared to the pre-contrast scan. No significant contrast enhancement was observed in the PVS in WM. The signal intensity difference between the PVS in the BG versus WM on pre-contrast images suggests that the fluid composition might be different between these PVSs. The difference in the contrast enhancement between the PVSs in the BG versus WM suggests a difference in drainage function.

  18. ULTRASTRUCTURAL ORGANIZATION OF CILIA AND BASAL BODIES OF THE EPITHELIUM OF THE CHOROID PLEXUS IN THE CHICK EMBRYO

    PubMed Central

    Doolin, Paul F.; Birge, Wesley J.

    1966-01-01

    Ultrastructural studies were performed on normal and abnormal cilia and basal bodies associated with the choroidal epithelium of the chick embryo. Tissues were prepared in each of several fixatives including: 1% osmium tetroxide, in both phosphate and veronal acetate buffers; 2% glutaraldehyde, followed by postfixation in osmium tetroxide; 1% potassium permanganate in veronal acetate buffer. Normal cilia display the typical pattern of 9 peripheral doublets and 2 central fibers, as well as a system of 9 secondary fibers. The latter show distinct interconnections between peripheral and central fibers. Supernumerary fibers were found to occur in certain abnormal cilia. The basal body is complex, bearing 9 transitional fibers at the distal end and numerous cross-striated rootlets at the proximal end. The distal end of the basal body is delimited by a basal plate of moderate density. The tubular cylinder consists of 9 triple fibers. The C subfibers end at the basal plate, whereas subfibers A and B continue into the shaft of the cilium. The 9 transitional fibers radiate out from the distal end of the basal body, ending in bulblike terminal enlargements which are closely associated with the cell membrane in the area of the basal cup. One or 2 prominent basal feet project laterally from the basal body. These structures characteristically show several dense cross-bands and, on occasion, are found associated with microtubules. PMID:5335827

  19. Feline mammary basal-like adenocarcinomas: a potential model for human triple-negative breast cancer (TNBC) with basal-like subtype.

    PubMed

    Wiese, David A; Thaiwong, Tuddow; Yuzbasiyan-Gurkan, Vilma; Kiupel, Matti

    2013-09-03

    Breast cancer is one of the leading causes of cancer deaths. Triple-negative breast cancer (TNBC), an immunophenotype defined by the absence of immunolabeling for estrogen receptor (ER), progesterone receptor (PR) and HER2 protein, has a highly aggressive behavior. A subpopulation of TNBCs exhibit a basal-like morphology with immunohistochemical positivity for cytokeratins 5/6 (CK5/6) and/or epidermal growth factor receptor (EGFR), and have a high incidence of BRCA (breast cancer susceptibility) mutations. Feline mammary adenocarcinomas (FMAs) are highly malignant and share a similar basal-like subtype. The purpose of this study was to classify FMAs according to the current human classification of breast cancer that includes evaluation of ER, PR and HER2 status and expression of basal CK 5/6 and EGFR. Furthermore, we selected triple negative, basal-like FMAs to screen for BRCA mutations similar to those described in human TNBC. Twenty four FMAs were classified according to the current human histologic breast cancer classification including immunohistochemistry (IHC) for ER, PR HER2, CK5/6 and EGFR. Genetic alteration and loss of heterozygosity of BRCA1 and BRCA2 genes were analyzed in triple negative, basal-like FMAs. IHC for ER, PR and HER2 identified 14 of the 24 (58%) FMAs as a triple negative. Furthermore, 11 of these 14 (79%) triple negative FMAs had a basal-like subtype. However, no genetic abnormalities were detected in BRCA1 and BRCA2 by direct sequencing and loss of heterozygosity analysis. FMAs are highly aggressive neoplasms that are commonly triple negative and exhibit a basal-like morphology. This is similar to human TNBC that are also commonly classified as a basal-like subtype. While sequencing of a select number of triple negative, basal-like FMAs and testing for loss of heterozygosity of BRCA1 and BRCA2 did not identify mutations similar to those described in human TNBC, further in-depth evaluation is required to elucidate a potential role of BRCA

  20. Altered local spontaneous activity in frontal lobe epilepsy: a resting-state functional magnetic resonance imaging study.

    PubMed

    Dong, Li; Li, Hechun; He, Zhongqiong; Jiang, Sisi; Klugah-Brown, Benjamin; Chen, Lin; Wang, Pu; Tan, Song; Luo, Cheng; Yao, Dezhong

    2016-11-01

    The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.

  1. Selected Gray Matter Volumes and Gender but Not Basal Ganglia nor Cerebellum Gyri Discriminate Left Versus Right Cerebral Hemispheres: Multivariate Analyses in human Brains at 3T.

    PubMed

    Roldan-Valadez, Ernesto; Suarez-May, Marcela A; Favila, Rafael; Aguilar-Castañeda, Erika; Rios, Camilo

    2015-07-01

    Interest in the lateralization of the human brain is evident through a multidisciplinary number of scientific studies. Understanding volumetric brain asymmetries allows the distinction between normal development stages and behavior, as well as brain diseases. We aimed to evaluate volumetric asymmetries in order to select the best gyri able to classify right- versus left cerebral hemispheres. A cross-sectional study performed in 47 right-handed young-adults healthy volunteers. SPM-based software performed brain segmentation, automatic labeling and volumetric analyses for 54 regions involving the cerebral lobes, basal ganglia and cerebellum from each cerebral hemisphere. Multivariate discriminant analysis (DA) allowed the assembling of a predictive model. DA revealed one discriminant function that significantly differentiated left vs. right cerebral hemispheres: Wilks' λ = 0.008, χ(2) (9) = 238.837, P < 0.001. The model explained 99.20% of the variation in the grouping variable and depicted an overall predictive accuracy of 98.8%. With the influence of gender; the selected gyri able to discriminate between hemispheres were middle orbital frontal gyrus (g.), angular g., supramarginal g., middle cingulum g., inferior orbital frontal g., calcarine g., inferior parietal lobule and the pars triangularis inferior frontal g. Specific brain gyri are able to accurately classify left vs. right cerebral hemispheres by using a multivariate approach; the selected regions correspond to key brain areas involved in attention, internal thought, vision and language; our findings favored the concept that lateralization has been evolutionary favored by mental processes increasing cognitive efficiency and brain capacity. © 2015 Wiley Periodicals, Inc.

  2. The vagal ganglia transcriptome identifies candidate therapeutics for airway hyperreactivity.

    PubMed

    Reznikov, Leah R; Meyerholz, David K; Abou Alaiwa, Mahmoud H; Kuan, Shin-Ping; Liao, Yan-Shin J; Bormann, Nicholas L; Bair, Thomas B; Price, Margaret; Stoltz, David A; Welsh, Michael J

    2018-04-05

    Mainstay therapeutics are ineffective in some people with asthma, suggesting a need for additional agents. In the current study, we used vagal ganglia transcriptome profiling and connectivity mapping to identify compounds beneficial for alleviating airway hyperreactivity. As a comparison, we also utilized previously published transcriptome data from sensitized mouse lungs and human asthmatic endobronchial biopsies. All transcriptomes revealed agents beneficial for mitigating airway hyperreactivity; however, only the vagal ganglia transcriptome identified agents used clinically to treat asthma (flunisolide, isoetarine). We also tested one compound identified by vagal ganglia transcriptome profiling that had not previously been linked to asthma and found that it had bronchodilator effects in both mouse and pig airways. These data suggest that transcriptome profiling of the vagal ganglia might be a novel strategy to identify potential asthma therapeutics.

  3. THE SIGNIFICANCE OF LESIONS IN PERIPHERAL GANGLIA IN CHIMPANZEE AND IN HUMAN POLIOMYELITIS

    PubMed Central

    Bodian, David; Howe, Howard A.

    1947-01-01

    1. The peripheral ganglia of eighteen inoculated chimpanzees and thirteen uninoculated controls, and of eighteen fatal human poliomyelitis cases, were studied for histopathological evidence of the route of transmission of virus from the alimentary tract to the CNS. 2. Lesions thought to be characteristic of poliomyelitis in inoculated chimpanzees could not be sharply differentiated from lesions of unknown origin in uninoculated control animals. Moreover, although the inoculated animals as a group, in comparison with the control animals, had a greater number of infiltrative lesions in sympathetic as well as in sensory ganglia, it was not possible to make satisfactory correlations between the distribution of these lesions and the routes of inoculation. 3. In sharp contrast with chimpanzees, the celiac and stellate ganglia of the human poliomyelitis cases were free of any but insignificant infiltrative lesions. Lesions in human trigeminal and spinal sensory ganglia included neuronal damage as well as focal and perivascular inflitrative lesions, as is well known. In most ganglia, as in monkey and chimpanzee sensory ganglia, these were correlated in intensify with the degree of severity of lesions in the region of the CNS receiving their axons. This suggested that lesions in sensory ganglia probably resulted from spread of virus centrifugally from the CNS, in accord with considerable experimental evidence. 4. Two principal difficulties in the interpretation of histopathological findings in peripheral ganglia were revealed by this study. The first is that the specificity of lesions in sympathetic ganglia has not been established beyond doubt as being due to poliomyelitis. The second is that the presence of characteristic lesions in sensory ganglia does not, and cannot, reveal whether the virus reached the ganglia from the periphery or from the central nervous system, except in very early preparalytic stages or in exceptional cases of early arrest of virus spread and of

  4. Cerebellar Influence on Motor Cortex Plasticity: Behavioral Implications for Parkinson’s Disease

    PubMed Central

    Kishore, Asha; Meunier, Sabine; Popa, Traian

    2014-01-01

    Normal motor behavior involves the creation of appropriate activity patterns across motor networks, enabling firing synchrony, synaptic integration, and normal functioning of these networks. Strong topography-specific connections among the basal ganglia, cerebellum, and their projections to overlapping areas in the motor cortices suggest that these networks could influence each other’s plastic responses and functions. The defective striatal signaling in Parkinson’s disease (PD) could therefore lead to abnormal oscillatory activity and aberrant plasticity at multiple levels within the interlinked motor networks. Normal striatal dopaminergic signaling and cerebellar sensory processing functions influence the scaling and topographic specificity of M1 plasticity. Both these functions are abnormal in PD and appear to contribute to the abnormal M1 plasticity. Defective motor map plasticity and topographic specificity within M1 could lead to incorrect muscle synergies, which could manifest as abnormal or undesired movements, and as abnormal motor learning in PD. We propose that the loss of M1 plasticity in PD reflects a loss of co-ordination among the basal ganglia, cerebellar, and cortical inputs which translates to an abnormal plasticity of motor maps within M1 and eventually to some of the motor signs of PD. The initial benefits of dopamine replacement therapy on M1 plasticity and motor signs are lost during the progressive course of disease. Levodopa-induced dyskinesias in patients with advanced PD is linked to a loss of M1 sensorimotor plasticity and the attenuation of dyskinesias by cerebellar inhibitory stimulation is associated with restoration of M1 plasticity. Complimentary interventions should target reestablishing physiological communication between the striatal and cerebellar circuits, and within striato-cerebellar loop. This may facilitate correct motor synergies and reduce abnormal movements in PD. PMID:24834063

  5. Short-Term Sleep Disturbance-Induced Stress Does not Affect Basal Pain Perception, but Does Delay Postsurgical Pain Recovery.

    PubMed

    Wang, Po-Kai; Cao, Jing; Wang, Hongzhen; Liang, Lingli; Zhang, Jun; Lutz, Brianna Marie; Shieh, Kun-Ruey; Bekker, Alex; Tao, Yuan-Xiang

    2015-11-01

    Chronic sleep disturbance-induced stress is known to increase basal pain sensitivity. However, most surgical patients frequently report short-term sleep disturbance/deprivation during the pre- and postoperation periods and have normal pain perception presurgery. Whether this short-term sleep disturbance affects postsurgical pain is elusive. Here, we report that pre- or postexposure to rapid eye movement sleep disturbance (REMSD) for 6 hours daily for 3 consecutive days did not alter basal responses to mechanical, heat, and cold stimuli, but did delay recovery in incision-induced reductions in paw withdrawal threshold to mechanical stimulation and paw withdrawal latencies to heat and cold stimuli on the ipsilateral side of male or female rats. This short-term REMSD led to stress shown by an increase in swim immobility time, a decrease in sucrose consumption, and an increase in the level of corticosterone in serum. Blocking this stress via intrathecal RU38486 or bilateral adrenalectomy abolished REMSD-caused delay in recovery of incision-induced reductions in behavioral responses to mechanical, heat, and cold stimuli. Moreover, this short-term REMSD produced significant reductions in the levels of mu opioid receptor and kappa opioid receptor, but not Kv1.2, in the ipsilateral L4/5 spinal cord and dorsal root ganglia on day 9 after incision (but not after sham surgery). Our findings show that short-term sleep disturbance either pre- or postsurgery does not alter basal pain perception, but does exacerbate postsurgical pain hypersensitivity. The latter may be related to the reductions of mu and kappa opioid receptors in the spinal cord and dorsal root ganglia caused by REMSD plus incision. Prevention of short-term sleep disturbance may help recovery from postsurgical pain in patients. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  6. Development of extracellular matrix in chick paravertebral sympathetic ganglia.

    PubMed

    Luckenbill-Edds, L

    1986-08-01

    Alcian blue staining coupled with enzyme digestion or critical electrolyte staining revealed differences in the development of extracellular matrix (ECM) within sympathetic ganglia compared with the surrounding capsule. On day 5 of chick development (Hamburger-Hamilton stage 26) only hyaluronic acid (HA) could be detected in the ECM surrounding condensing primary ganglia. By day 7 (st 30) the ganglionic capsule contained HA, as well as sulfated glycosaminoglycans (GAGs), and this pattern continued into the adult stage. During the later stages of embryonic life (st 41-45) satellite cells appear, showing fine structural characteristics that point to their role in the secretion of intraganglionic ECM. Only during these stages could ECM be detected histochemically within ganglia, the same stages (days 15-19) when routine electron microscopic methods reveal collagen fibrils embedded in a granular ground substance. Thus, the intraganglionic environment appears as a separate compartment free of detectable amounts of GAG until late embryonic stages when ECM is secreted around satellite cells. This developmental pattern could represent a role of ECM in the histological stabilization of ganglia during the late stages of differentiation, since the appearance of intraganglionic ECM is correlated with the appearance of small dense-cored vesicles characteristic of adult neurons. The developmental pattern of ECM in differentiating sympathetic ganglia is compared with that of other tissues that undergo condensation and morphogenesis.

  7. Basal forebrain amnesia: does the nucleus accumbens contribute to human memory?

    PubMed Central

    Goldenberg, G.; Schuri, U.; Gromminger, O.; Arnold, U.

    1999-01-01

    OBJECTIVE—To analyse amnesia caused by basal forebrain lesions.
METHODS—A single case study of a patient with amnesia after bleeding into the anterior portion of the left basal ganglia. Neuropsychological examination included tests of attention, executive function, working memory, recall, and recognition of verbal and non-verbal material, and recall from remote semantic and autobiographical memory. The patient's MRI and those of other published cases of basal forebrain amnesia were reviewed to specify which structures within the basal forebrain are crucial for amnesia.
RESULTS—Attention and executive function were largely intact. There was anterograde amnesia for verbal material which affected free recall and recognition. With both modes of testing the patient produced many false positive responses and intrusions when lists of unrelated words had been memorised. However, he confabulated neither on story recall nor in day to day memory, nor in recall from remote memory. The lesion affected mainly the nucleus accumbens, but encroached on the inferior limb of the capsula interna and the most ventral portion of the nucleus caudatus and globus pallidus, and there was evidence of some atrophy of the head of the caudate nucleus. The lesion spared the nucleus basalis Meynert, the diagnonal band, and the septum, which are the sites of cholinergic cell concentrations.
CONCLUSIONS—It seems unlikely that false positive responses were caused by insufficient strategic control of memory retrieval. This speaks against a major role of the capsular lesion which might disconnect the prefrontal cortex from the thalamus. It is proposed that the lesion of the nucleus accumbens caused amnesia.

 PMID:10406982

  8. The role of 99Tcm-HMPAO brain SPET in paediatric traumatic brain injury.

    PubMed

    Goshen, E; Zwas, S T; Shahar, E; Tadmor, R

    1996-05-01

    Twenty-eight paediatric patients suffering from chronic sequelae of traumatic brain injury (TBI) were examined by EEG, radionuclide imaging with 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO), computed tomography (CT) and, when available, magnetic resonance imaging (MRI), the results of which were evaluated retrospectively. Our findings indicate that neuro-SPET (single photon emission tomography) with 99Tcm-HMPAO is more sensitive than morphological or electrophysiological tests in detecting functional lesions. In our group, 15 of 32 CT scans were normal, compared with 3 of 35 SPET studies. SPET identified approximately 2.5 times more lesions than CT (86 vs 34). SPET was found to be particularly sensitive in detecting organic abnormalities in the basal ganglia and cerebellar regions, with a 3.6:1 detection rate in the basal ganglia and a 5:1 detection rate in the cerebellum compared with CT. In conclusion, neuro-SPET appears to be very useful when evaluating paediatric post-TBI patients in whom other modalities are not successful.

  9. [Distribution of herpes simplex virus type 1 and 2 genomes in the human spinal ganglia].

    PubMed

    Obara, Y

    1994-09-01

    Herpes simplex virus (HSV) is well known for its propensity to cause recurrent oral or genital mucosal infections in humans. HSV-1 is involved primarily in oral lesions, whereas HSV-2 is more frequently involved in genital lesions. Based on this, it is thought that HSV-1 may produce latent infections in trigeminal ganglia, and HSV-2 in the sacral ganglia. However the distribution pattern of latent HSV-1 and HSV-2 infections in spinal ganglia remains unknown. Using the polymerase chain reaction we detected latent herpes HSV-1 and HSV-2 in human spinal ganglia obtained from autopsy material. A pair of primers which were specific for a part of the HSV-1 and HSV-2 DNA polymerase domain were employed. HSV-1 and HSV-2 DNAs were detected in 11 of 40 (28%) and 15 of 40 (38%) cervical ganglia, respectively, 52 of 103 (50%) and 47 of 103 (46%) thoracic ganglia, 16 of 53 (30%) and 17 of 53 (32%) lumbar ganglia, and 3 of 20 (15%) and 3 of 20 (15%) sacral ganglia. These findings suggest that latent HSV-1 and HSV-2 infections have a widespread distribution from the cervical ganglia to sacral ganglia. Importantly this study demonstrated latent HSV-1 infection of both the lumbar and sacral ganglia for the first time.

  10. Disorders of Upper Limb Movements in Ataxia-Telangiectasia.

    PubMed

    Shaikh, Aasef G; Zee, David S; Mandir, Allen S; Lederman, Howard M; Crawford, Thomas O

    2013-01-01

    Ataxia-telangiectasia is known for cerebellar degeneration, but clinical descriptions of abnormal tone, posture, and movements suggest involvement of the network between cerebellum and basal ganglia. We quantitatively assessed the nature of upper-limb movement disorders in ataxia-telangiectasia. We used a three-axis accelerometer to assess the natural history and severity of abnormal upper-limb movements in 80 ataxia-telangiectasia and 19 healthy subjects. Recordings were made during goal-directed movements of upper limb (kinetic task), while arms were outstretched (postural task), and at rest. Almost all ataxia-telangiectasia subjects (79/80) had abnormal involuntary movements, such as rhythmic oscillations (tremor), slow drifts (dystonia or athetosis), and isolated rapid movements (dystonic jerks or myoclonus). All patients with involuntary movements had both kinetic and postural tremor, while 48 (61%) also had resting tremor. The tremor was present in transient episodes lasting several seconds during two-minute recording sessions of all three conditions. Percent time during which episodic tremor was present was greater for postural and kinetic tasks compared to rest. Resting tremor had higher frequency but smaller amplitude than postural and kinetic tremor. Rapid non-rhythmic movements were minimal during rest, but were triggered during sustained arm postures and goal directed arm movements suggesting they are best considered a form of dystonic jerks or action myoclonus. Advancing age did not correlate with the severity of involuntary limb movements. Abnormal upper-limb movements in ataxia-telangiectasia feature classic cerebellar impairment, but also suggest involvement of the network between the cerebellum and basal ganglia.

  11. Disorders of Upper Limb Movements in Ataxia-Telangiectasia

    PubMed Central

    Shaikh, Aasef G.; Zee, David S.; Mandir, Allen S.; Lederman, Howard M.; Crawford, Thomas O.

    2013-01-01

    Ataxia-telangiectasia is known for cerebellar degeneration, but clinical descriptions of abnormal tone, posture, and movements suggest involvement of the network between cerebellum and basal ganglia. We quantitatively assessed the nature of upper-limb movement disorders in ataxia-telangiectasia. We used a three-axis accelerometer to assess the natural history and severity of abnormal upper-limb movements in 80 ataxia-telangiectasia and 19 healthy subjects. Recordings were made during goal-directed movements of upper limb (kinetic task), while arms were outstretched (postural task), and at rest. Almost all ataxia-telangiectasia subjects (79/80) had abnormal involuntary movements, such as rhythmic oscillations (tremor), slow drifts (dystonia or athetosis), and isolated rapid movements (dystonic jerks or myoclonus). All patients with involuntary movements had both kinetic and postural tremor, while 48 (61%) also had resting tremor. The tremor was present in transient episodes lasting several seconds during two-minute recording sessions of all three conditions. Percent time during which episodic tremor was present was greater for postural and kinetic tasks compared to rest. Resting tremor had higher frequency but smaller amplitude than postural and kinetic tremor. Rapid non-rhythmic movements were minimal during rest, but were triggered during sustained arm postures and goal directed arm movements suggesting they are best considered a form of dystonic jerks or action myoclonus. Advancing age did not correlate with the severity of involuntary limb movements. Abnormal upper-limb movements in ataxia-telangiectasia feature classic cerebellar impairment, but also suggest involvement of the network between the cerebellum and basal ganglia. PMID:23826191

  12. Periosteal ganglia: CT and MR imaging features.

    PubMed

    Abdelwahab, I F; Kenan, S; Hermann, G; Klein, M J; Lewis, M M

    1993-07-01

    The imaging features of four cases of periosteal ganglia were studied. Three lesions were located over the proximal shaft of the tibia, in proximity to the pes anserinus. The fourth lesion involved the distal shaft of the ulna. Three lesions had different degrees of external cortical erosion, scalloping, and thick spicules of periosteal bone on plain radiographs. The bone adjacent to the fourth lesion was not involved. Computed tomography (CT) showed these lesions to be sharply defined soft-tissue masses abutting the periosteum. All of the lesions had the same attenuation as fluid. Magnetic resonance (MR) imaging revealed the ganglia to be sharply defined masses that were isointense compared with neighboring muscles on T1-weighted images. There was markedly increased signal intensity compared with that of fat on T2-weighted images. The signal intensity on both types of images was homogeneous. The MR imaging features were consistent with the fluid nature of the lesions. Under the appropriate clinical circumstances, the MR imaging and CT features of periosteal ganglia are diagnostic.

  13. High-frequency stimulation of the subthalamic nucleus modifies the expression of vesicular glutamate transporters in basal ganglia in a rat model of Parkinson's disease.

    PubMed

    Favier, Mathieu; Carcenac, Carole; Drui, Guillaume; Boulet, Sabrina; El Mestikawy, Salah; Savasta, Marc

    2013-12-05

    It has been suggested that glutamatergic system hyperactivity may be related to the pathogenesis of Parkinson's disease (PD). Vesicular glutamate transporters (VGLUT1-3) import glutamate into synaptic vesicles and are key anatomical and functional markers of glutamatergic excitatory transmission. Both VGLUT1 and VGLUT2 have been identified as definitive markers of glutamatergic neurons, but VGLUT 3 is also expressed by non glutamatergic neurons. VGLUT1 and VGLUT2 are thought to be expressed in a complementary manner in the cortex and the thalamus (VL/VM), in glutamatergic neurons involved in different physiological functions. Chronic high-frequency stimulation (HFS) of the subthalamic nucleus (STN) is the neurosurgical therapy of choice for the management of motor deficits in patients with advanced PD. STN-HFS is highly effective, but its mechanisms of action remain unclear. This study examines the effect of STN-HFS on VGLUT1-3 expression in different brain nuclei involved in motor circuits, namely the basal ganglia (BG) network, in normal and 6-hydroxydopamine (6-OHDA) lesioned rats. Here we report that: 1) Dopamine(DA)-depletion did not affect VGLUT1 and VGLUT3 expression but significantly decreased that of VGLUT2 in almost all BG structures studied; 2) STN-HFS did not change VGLUT1-3 expression in the different brain areas of normal rats while, on the contrary, it systematically induced a significant increase of their expression in DA-depleted rats and 3) STN-HFS reversed the decrease in VGLUT2 expression induced by the DA-depletion. These results show for the first time a comparative analysis of changes of expression for the three VGLUTs induced by STN-HFS in the BG network of normal and hemiparkinsonian rats. They provide evidence for the involvement of VGLUT2 in the modulation of BG cicuits and in particular that of thalamostriatal and thalamocortical pathways suggesting their key role in its therapeutic effects for alleviating PD motor symptoms.

  14. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome)

    PubMed Central

    Kiran, N. K.; Tilak Raj, T. N.; Mukunda, K. S.; Rajashekar Reddy, V.

    2012-01-01

    The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient. PMID:23633824

  15. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome).

    PubMed

    Kiran, N K; Tilak Raj, T N; Mukunda, K S; Rajashekar Reddy, V

    2012-10-01

    The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

  16. [A report of atypical hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum caused by a de novo mutation in tubulin beta 4A (TUBB4A) gene and literature review].

    PubMed

    Du, Y; Li, C; Guo, J; Guo, P; Li, Z Y; Zhang, W

    2017-06-01

    Objective: To explore the clinical symptoms and neuroimaging features of a patient with atypical hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum (H-ABC) caused by a novel TUBB4A mutation. Methods: We analyzed the clinical data, imaging features and the result of genetic testing of a case diagnosed as atypical H-ABC. Results: The initial symptoms were progressive spasticity, mild cerebellar ataxia and mild cognitive impairment. MRI showed regional blurring of slight high signal on T(2)-weight and FLAIR image in white matter of the bilateral midbrain ventral, internal capsule, posteior horn of lateral ventricle and centrum semiovale, with normal bilateral cerebellar and caudoputamen nucleus. Compared with normal subjects of the same age and gender, hypometabolism was found by (18)F-FDG-PET in brainstem, cerebellar and caudoputamen nucleus in the patient. Genetic testing revealed a de novo pathogenic exome missense heterozygous mutations c. 70G>A in TUBB4A, which was not reported in the human gene mutation database (HGMDpro) and was assessed to be a pathogenic mutation by pathogenic mutation prediction software. Conclusions: The diversity of TUBB4A gene mutations may cause different functional and/or structural impairment in subcortical white matter, cerebellar and caudoputamen nucleus, leading to atypical symptoms and neuroimaging features. Genetic testing for pathogenic mutation in TUBB 4A gene is a key for the diagnosis of H - ABC .

  17. Dorsal root ganglia volume differentiates schwannomatosis and neurofibromatosis 2.

    PubMed

    Godel, Tim; Mautner, Victor-Felix; Farschtschi, Said; Pham, Mirko; Schwarz, Daniel; Kronlage, Moritz; Gugel, Isabel; Heiland, Sabine; Bendszus, Martin; Bäumer, Philipp

    2018-04-01

    Schwannomatosis and neurofibromatosis type 2 are hereditary tumor syndromes, and peripheral neuropathy has been reported in both. We prospectively applied in vivo morphometric measurement of dorsal root ganglia volume in 16 schwannomatosis patients, 14 neurofibromatosis type 2 patients, and 26 healthy controls by magnetic resonance neurography. Compared to healthy controls, dorsal root ganglia hypertrophy was a consistent finding in neurofibromatosis type 2 (L3, + 267%; L4, + 235%; L5, + 241%; S1, + 300%; S2, + 242%; Bonferroni-adjusted p < 0.001) but not in schwannomatosis. Dorsal root ganglia may be a vulnerable site in origination of areflexia and sensory loss and a useful diagnostic marker in neurofibromatosis type 2. Ann Neurol 2018;83:854-857. © 2018 American Neurological Association.

  18. Airway Basal Cells. The “Smoking Gun” of Chronic Obstructive Pulmonary Disease

    PubMed Central

    2014-01-01

    The earliest abnormality in the lung associated with smoking is hyperplasia of airway basal cells, the stem/progenitor cells of the ciliated and secretory cells that are central to pulmonary host defense. Using cell biology and ’omics technologies to assess basal cells isolated from bronchoscopic brushings of nonsmokers, smokers, and smokers with chronic obstructive pulmonary disease (COPD), compelling evidence has been provided in support of the concept that airway basal cells are central to the pathogenesis of smoking-associated lung diseases. When confronted by the chronic stress of smoking, airway basal cells become disorderly, regress to a more primitive state, behave as dictated by their inheritance, are susceptible to acquired changes in their genome, lose the capacity to regenerate the epithelium, are responsible for the major changes in the airway that characterize COPD, and, with persistent stress, can undergo malignant transformation. Together, these observations led to the conclusion that accelerated loss of lung function in susceptible individuals begins with disordered airway basal cell biology (i.e., that airway basal cells are the “smoking gun” of COPD, a potential target for the development of therapies to prevent smoking-related lung disorders). PMID:25354273

  19. Pathogenesis and neuroimaging of cerebral large and small vessel disease in type 2 diabetes: A possible link between cerebral and retinal microvascular abnormalities.

    PubMed

    Umemura, Toshitaka; Kawamura, Takahiko; Hotta, Nigishi

    2017-03-01

    Diabetes patients have more than double the risk of ischemic stroke compared with non-diabetic individuals, and its neuroimaging characteristics have important clinical implications. To understand the pathophysiology of ischemic stroke in diabetes, it is important to focus not only on the stroke subtype, but also on the size and location of the occlusive vessels. Specifically, ischemic stroke in diabetes patients might be attributed to both large and small vessels, and intracranial internal carotid artery disease and small infarcts of the posterior circulation often occur. An additional feature is that asymptomatic lacunar infarctions are often seen in the basal ganglia and brain stem on brain magnetic resonance imaging. In particular, cerebral small vessel disease (SVD), including lacunar infarctions, white matter lesions and cerebral microbleeds, has been shown to be associated not only with stroke incidence, but also with the development and progression of dementia and diabetic microangiopathy. However, the pathogenesis of cerebral SVD is not fully understood. In addition, data on the association between neuroimaging findings of the cerebral SVD and diabetes are limited. Recently, the clinical importance of the link between cerebral SVD and retinal microvascular abnormalities has been a topic of considerable interest. Several clinical studies have shown that retinal microvascular abnormalities are closely related to cerebral SVD, suggesting that retinal microvascular abnormalities might be pathophysiologically linked to ischemic cerebral SVD. We review the literature relating to the pathophysiology and neuroimaging of cerebrovascular disease in diabetes, and discuss the problems based on the concept of cerebral large and small vessel disease. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  20. Analysis of T Cell Responses during Active Varicella-Zoster Virus Reactivation in Human Ganglia

    PubMed Central

    Steain, Megan; Sutherland, Jeremy P.; Rodriguez, Michael; Cunningham, Anthony L.; Slobedman, Barry

    2014-01-01

    ABSTRACT Varicella-zoster virus (VZV) is responsible for both varicella (chickenpox) and herpes zoster (shingles). During varicella, the virus establishes latency within the sensory ganglia and can reactivate to cause herpes zoster, but the immune responses that occur in ganglia during herpes zoster have not previously been defined. We examined ganglia obtained from individuals who, at the time of death, had active herpes zoster. Ganglia innervating the site of the cutaneous herpes zoster rash showed evidence of necrosis, secondary to vasculitis, or localized hemorrhage. Despite this, there was limited evidence of VZV antigen expression, although a large inflammatory infiltrate was observed. Characterization of the infiltrating T cells showed a large number of infiltrating CD4+ T cells and cytolytic CD8+ T cells. Many of the infiltrating T cells were closely associated with neurons within the reactivated ganglia, yet there was little evidence of T cell-induced neuronal apoptosis. Notably, an upregulation in the expression of major histocompatibility complex class I (MHC-I) and MHC-II molecules was observed on satellite glial cells, implying these cells play an active role in directing the immune response during herpes zoster. This is the first detailed characterization of the interaction between T cells and neuronal cells within ganglia obtained from patients suffering herpes zoster at the time of death and provides evidence that CD4+ and cytolytic CD8+ T cell responses play an important role in controlling VZV replication in ganglia during active herpes zoster. IMPORTANCE VZV is responsible for both varicella (chickenpox) and herpes zoster (shingles). During varicella, the virus establishes a life-long dormant infection within the sensory ganglia and can reawaken to cause herpes zoster, but the immune responses that occur in ganglia during herpes zoster have not previously been defined. We examined ganglia obtained from individuals who, at the time of death, had

  1. Risk of ultrasound-detected neonatal brain abnormalities in intrauterine growth-restricted fetuses born between 28 and 34 weeks' gestation: relationship with gestational age at birth and fetal Doppler parameters.

    PubMed

    Cruz-Martinez, R; Tenorio, V; Padilla, N; Crispi, F; Figueras, F; Gratacos, E

    2015-10-01

    To estimate the value of gestational age at birth and fetal Doppler parameters in predicting the risk of neonatal cranial abnormalities in intrauterine growth-restricted (IUGR) fetuses born between 28 and 34 weeks' gestation. Fetal Doppler parameters including umbilical artery (UA), middle cerebral artery (MCA), aortic isthmus, ductus venosus and myocardial performance index were evaluated in a cohort of 90 IUGR fetuses with abnormal UA Doppler delivered between 28 and 34 weeks' gestation and in 90 control fetuses matched for gestational age. The value of gestational age at birth and fetal Doppler parameters in predicting the risk of ultrasound-detected cranial abnormalities (CUA), including intraventricular hemorrhage, periventricular leukomalacia and basal ganglia lesions, was analyzed. Overall, IUGR fetuses showed a significantly higher incidence of CUA than did control fetuses (40.0% vs 12.2%, respectively; P < 0.001). Within the IUGR group, all predictive variables were associated individually with the risk of CUA, but fetal Doppler parameters rather than gestational age at birth were identified as the best predictor. MCA Doppler distinguished two groups with different degrees of risk of CUA (48.5% vs 13.6%, respectively; P < 0.01). In the subgroup with MCA vasodilation, presence of aortic isthmus retrograde net blood flow, compared to antegrade flow, allowed identification of a subgroup of cases with the highest risk of CUA (66.7% vs 38.6%, respectively; P < 0.05). Evaluation of fetal Doppler parameters, rather than gestational age at birth, allows identification of IUGR preterm fetuses at risk of neonatal brain abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  2. Abnormal mitochondrial respiration in failed human myocardium.

    PubMed

    Sharov, V G; Todor, A V; Silverman, N; Goldstein, S; Sabbah, H N

    2000-12-01

    Chronic heart failure (HF) is associated with morphologic abnormalities of cardiac mitochondria including hyperplasia, reduced organelle size and compromised structural integrity. In this study, we examined whether functional abnormalities of mitochondrial respiration are also present in myocardium of patients with advanced HF. Mitochondrial respiration was examined using a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles obtained from myocardium of failed explanted human hearts due to ischemic (ICM, n=9) or idiopathic dilated (IDC, n=9) cardiomyopathy. Myocardial specimens from five normal donor hearts served as controls (CON). Basal respiratory rate, respiratory rate after addition of the substrates glutamate and malate (V(SUB)), state 3 respiration (after addition of ADP, V(ADP)) and respiration after the addition of atractyloside (V(AT)) were measured in scar-free muscle bundles obtained from the subendocardial (ENDO) and subepicardial (EPI) thirds of the left ventricular (LV) free wall, interventricular septum and right ventricular (RV) free wall. There were no differences in basal and substrate-supported respiration between CON and HF regardless of etiology. V(ADP)was significantly depressed both in ICM and IDC compared to CON in all the regions studied. The respiratory control ratio, V(ADP)/V(AT), was also significantly decreased in HF compared to CON. In both ICM and IDC, V(ADP)was significantly lower in ENDO compared to EPI. The results indicate that mitochondrial respiration is abnormal in the failing human heart. The findings support the concept of low myocardial energy production in HF via oxidative phosphorylation, an abnormality with a potentially impact on global cardiac performance. Copyright 2000 Academic Press.

  3. The intralaminar thalamus—an expressway linking visual stimuli to circuits determining agency and action selection

    PubMed Central

    Fisher, Simon D.; Reynolds, John N. J.

    2014-01-01

    Anatomical investigations have revealed connections between the intralaminar thalamic nuclei and areas such as the superior colliculus (SC) that receive short latency input from visual and auditory primary sensory areas. The intralaminar nuclei in turn project to the major input nucleus of the basal ganglia, the striatum, providing this nucleus with a source of subcortical excitatory input. Together with a converging input from the cerebral cortex, and a neuromodulatory dopaminergic input from the midbrain, the components previously found necessary for reinforcement learning in the basal ganglia are present. With this intralaminar sensory input, the basal ganglia are thought to play a primary role in determining what aspect of an organism’s own behavior has caused salient environmental changes. Additionally, subcortical loops through thalamic and basal ganglia nuclei are proposed to play a critical role in action selection. In this mini review we will consider the anatomical and physiological evidence underlying the existence of these circuits. We will propose how the circuits interact to modulate basal ganglia output and solve common behavioral learning problems of agency determination and action selection. PMID:24765070

  4. Neural correlates underlying micrographia in Parkinson’s disease

    PubMed Central

    Zhang, Jiarong; Hallett, Mark; Feng, Tao; Hou, Yanan; Chan, Piu

    2016-01-01

    Micrographia is a common symptom in Parkinson’s disease, which manifests as either a consistent or progressive reduction in the size of handwriting or both. Neural correlates underlying micrographia remain unclear. We used functional magnetic resonance imaging to investigate micrographia-related neural activity and connectivity modulations. In addition, the effect of attention and dopaminergic administration on micrographia was examined. We found that consistent micrographia was associated with decreased activity and connectivity in the basal ganglia motor circuit; while progressive micrographia was related to the dysfunction of basal ganglia motor circuit together with disconnections between the rostral supplementary motor area, rostral cingulate motor area and cerebellum. Attention significantly improved both consistent and progressive micrographia, accompanied by recruitment of anterior putamen and dorsolateral prefrontal cortex. Levodopa improved consistent micrographia accompanied by increased activity and connectivity in the basal ganglia motor circuit, but had no effect on progressive micrographia. Our findings suggest that consistent micrographia is related to dysfunction of the basal ganglia motor circuit; while dysfunction of the basal ganglia motor circuit and disconnection between the rostral supplementary motor area, rostral cingulate motor area and cerebellum likely contributes to progressive micrographia. Attention improves both types of micrographia by recruiting additional brain networks. Levodopa improves consistent micrographia by restoring the function of the basal ganglia motor circuit, but does not improve progressive micrographia, probably because of failure to repair the disconnected networks. PMID:26525918

  5. On the Origin of Tremor in Parkinson’s Disease

    PubMed Central

    Dovzhenok, Andrey; Rubchinsky, Leonid L.

    2012-01-01

    The exact origin of tremor in Parkinson’s disease remains unknown. We explain why the existing data converge on the basal ganglia-thalamo-cortical loop as a tremor generator and consider a conductance-based model of subthalamo-pallidal circuits embedded into a simplified representation of the basal ganglia-thalamo-cortical circuit to investigate the dynamics of this loop. We show how variation of the strength of dopamine-modulated connections in the basal ganglia-thalamo-cortical loop (representing the decreasing dopamine level in Parkinson’s disease) leads to the occurrence of tremor-like burst firing. These tremor-like oscillations are suppressed when the connections are modulated back to represent a higher dopamine level (as it would be the case in dopaminergic therapy), as well as when the basal ganglia-thalamo-cortical loop is broken (as would be the case for ablative anti-parkinsonian surgeries). Thus, the proposed model provides an explanation for the basal ganglia-thalamo-cortical loop mechanism of tremor generation. The strengthening of the loop leads to tremor oscillations, while the weakening or disconnection of the loop suppresses them. The loop origin of parkinsonian tremor also suggests that new tremor-suppression therapies may have anatomical targets in different cortical and subcortical areas as long as they are within the basal ganglia-thalamo-cortical loop. PMID:22848541

  6. Nicergoline increases serum substance P levels in patients with an ischaemic stroke.

    PubMed

    Nishiyama, Yasuhiro; Abe, Arata; Ueda, Masayuki; Katsura, Ken-ichiro; Katayama, Yasuo

    2010-01-01

    Aspiration pneumonia is one of the most important complications following ischaemic stroke, and a leading cause of mortality in stroke patients. This is particularly prevalent in patients with involvement of the basal ganglia, which may be due to impaired neurotransmission through lack of production of substance P. Consecutive patients in the chronic stage, 1-3 months after cerebral ischaemic infarction, were assessed for basal ganglia involvement by magnetic resonance imaging. The patients were randomised to 4 weeks of treatment with (n = 25) or without (n = 25) nicergoline (15 mg t.i.d.). Serum concentration of substance P was measured by radioimmunoassay. At entry to the study, mean concentration of substance P was significantly (p < 0.001) lower in patients with bilateral basal ganglia lesions than in patients with no or unilateral basal ganglia involvement. Nicergoline administration caused a significant (p = 0.021) increase from baseline in mean substance P concentration. No significant change was seen in the nicergoline-untreated patients (p = 0.626). Among the patients who received nicergoline, 11 patients had bilateral basal ganglia involvement and there was no significant mean change in substance P in these patients, whereas there was a significant increase (p = 0.032) in the 14 nicergoline-treated patients with no or unilateral basal ganglia involvement. The present study suggests a possible effect of nicergoline to increase substance P level in ischaemic stroke patients with partial damage to basal ganglia, who have a decreased swallowing response and consequent risk of aspiration pneumonia. Further trials of nicergoline treatment in patients at risk for aspiration pneumonia are warranted. (c) 2009 S. Karger AG, Basel.

  7. [A comparative analysis of anti-N-methyl-D-aspartate receptor encephalitis with or without abnormal findings on cranial magnetic resonance imaging].

    PubMed

    Zhang, Jian-Zhao; Chen, Qian; Zheng, Ping; Xie, Li-Na; Yi, Xiao-Li; Ren, Hai-Tao; Yang, Jian

    2018-01-01

    To investigate the clinical features of children with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis with normal or abnormal cranial magnetic resonance imaging (MRI) findings via a comparative analysis. A retrospective analysis was performed for the clinical data of 33 children with anti-NMDAR encephalitis. The clinical features and prognosis were compared between the children with normal and abnormal cranial MRI findings. In the 33 children with anti-NMDAR encephalitis, the most common initial symptoms were seizures (61%) and involuntary movement (61%), followed by language disorder (54%), mental and behavioral abnormalities (52%), and disturbance of consciousness (30%). All children had positive anti-NMDAR antibody in the cerebrospinal fluid, and 29 children (88%) had positive serum antibody. Of all the children, 15 (46%) had increased leukocytes in the cerebrospinal fluid, 3 (9%) had an increase in protein, and 29 (88%) had positive oligoclonal band; 26 children (79%) had electroencephalographic abnormalities (epileptic wave, slow wave, or a combination of these two types of waves). One child experienced respiratory failure. One child was found to have germinoma in the sellar region during follow-up. Of all the 33 children, 13 (39%) had abnormal cranial MRI findings, with hypointensity or isointensity on T1W1 and hyperintensity on T2WI and T2-FLAIR; 2 children had dural enhancement. As for the location of lesion, 5 children (38%) had lesions in the temporal lobe, 3 (23%) in the frontal lobe, 3 (23%) in the basal ganglia, 2 (15%) in the parietal lobe, 2 (15%) in the occipital lobe, 2 (15%) in the brainstem, 1 (8%) in the thalamus, and 1 (8%) in the cerebellum. Among the 13 children with abnormal cranial MRI findings, 5 (38%) had lesions mainly in the grey matter and 8 (62%) had lesions mainly in the white matter. Compared with the children with normal cranial MRI findings, the children with abnormal cranial MRI findings had significantly higher

  8. Comprehensive RNA-Seq Expression Analysis of Sensory Ganglia with a Focus on Ion Channels and GPCRs in Trigeminal Ganglia

    PubMed Central

    Manteniotis, Stavros; Lehmann, Ramona; Flegel, Caroline; Vogel, Felix; Hofreuter, Adrian; Schreiner, Benjamin S. P.; Altmüller, Janine; Becker, Christian; Schöbel, Nicole; Hatt, Hanns; Gisselmann, Günter

    2013-01-01

    The specific functions of sensory systems depend on the tissue-specific expression of genes that code for molecular sensor proteins that are necessary for stimulus detection and membrane signaling. Using the Next Generation Sequencing technique (RNA-Seq), we analyzed the complete transcriptome of the trigeminal ganglia (TG) and dorsal root ganglia (DRG) of adult mice. Focusing on genes with an expression level higher than 1 FPKM (fragments per kilobase of transcript per million mapped reads), we detected the expression of 12984 genes in the TG and 13195 in the DRG. To analyze the specific gene expression patterns of the peripheral neuronal tissues, we compared their gene expression profiles with that of the liver, brain, olfactory epithelium, and skeletal muscle. The transcriptome data of the TG and DRG were scanned for virtually all known G-protein-coupled receptors (GPCRs) as well as for ion channels. The expression profile was ranked with regard to the level and specificity for the TG. In total, we detected 106 non-olfactory GPCRs and 33 ion channels that had not been previously described as expressed in the TG. To validate the RNA-Seq data, in situ hybridization experiments were performed for several of the newly detected transcripts. To identify differences in expression profiles between the sensory ganglia, the RNA-Seq data of the TG and DRG were compared. Among the differentially expressed genes (> 1 FPKM), 65 and 117 were expressed at least 10-fold higher in the TG and DRG, respectively. Our transcriptome analysis allows a comprehensive overview of all ion channels and G protein-coupled receptors that are expressed in trigeminal ganglia and provides additional approaches for the investigation of trigeminal sensing as well as for the physiological and pathophysiological mechanisms of pain. PMID:24260241

  9. [Repetitive phenomenona in the spontaneous speech of aphasic patients: perseveration, stereotypy, echolalia, automatism and recurring utterance].

    PubMed

    Wallesch, C W; Brunner, R J; Seemüller, E

    1983-12-01

    Repetitive phenomena in spontaneous speech were investigated in 30 patients with chronic infarctions of the left hemisphere which included Broca's and/or Wernicke's area and/or the basal ganglia. Perseverations, stereotypies, and echolalias occurred with all types of brain lesions, automatisms and recurring utterances only with those patients, whose infarctions involved Wernicke's area and basal ganglia. These patients also showed more echolalic responses. The results are discussed in view of the role of the basal ganglia as motor program generators.

  10. Local GABAergic signaling within sensory ganglia controls peripheral nociceptive transmission

    PubMed Central

    Du, Xiaona; Hao, Han; Yang, Yuehui; Huang, Sha; Wang, Caixue; Gigout, Sylvain; Ramli, Rosmaliza; Li, Xinmeng; Jaworska, Ewa; Edwards, Ian; Yanagawa, Yuchio; Qi, Jinlong; Guan, Bingcai; Jaffe, David B.; Zhang, Hailin

    2017-01-01

    The integration of somatosensory information is generally assumed to be a function of the central nervous system (CNS). Here we describe fully functional GABAergic communication within rodent peripheral sensory ganglia and show that it can modulate transmission of pain-related signals from the peripheral sensory nerves to the CNS. We found that sensory neurons express major proteins necessary for GABA synthesis and release and that sensory neurons released GABA in response to depolarization. In vivo focal infusion of GABA or GABA reuptake inhibitor to sensory ganglia dramatically reduced acute peripherally induced nociception and alleviated neuropathic and inflammatory pain. In addition, focal application of GABA receptor antagonists to sensory ganglia triggered or exacerbated peripherally induced nociception. We also demonstrated that chemogenetic or optogenetic depolarization of GABAergic dorsal root ganglion neurons in vivo reduced acute and chronic peripherally induced nociception. Mechanistically, GABA depolarized the majority of sensory neuron somata, yet produced a net inhibitory effect on the nociceptive transmission due to the filtering effect at nociceptive fiber T-junctions. Our findings indicate that peripheral somatosensory ganglia represent a hitherto underappreciated site of somatosensory signal integration and offer a potential target for therapeutic intervention. PMID:28375159

  11. CYTOLOGICAL STUDIES OF ORGANOTYPIC CULTURES OF RAT DORSAL ROOT GANGLIA FOLLOWING X-IRRADIATION IN VITRO

    PubMed Central

    Masurovsky, Edmund B.; Bunge, Mary Bartlett; Bunge, Richard P.

    1967-01-01

    Long-term organotypic cultures of rat dorsal root ganglia were exposed to a single 40 kR dose of 184 kvp X-rays and studied in the living and fixed states by light or electron microscopy at 1–14 day intervals thereafter. Within the first 4 days following irradiation, over 30% of the neurons display chromatolytic reactions (eccentric nuclei, peripheral dispersal of Nissl substance, central granular zone) as well as abnormal nucleolar changes and dissociation of ribosomes from endoplasmic reticulum cisternae. Some satellite cells undergo retraction or acute degeneration, leaving only basement membrane to cover the neuron in these areas. 8 days after irradiation, neurons also exhibit (a) areas in which ribosomes are substantially reduced, (b) regions of cytoplasmic sequestration, (c) extensive vacuolization of granular endoplasmic reticulum and Golgi complex, and (d) diversely altered mitochondria (including the presence of ribosome-like particles or association with abnormal glycogen and lipid deposits). Nucleolar components become altered or reoriented and may form abnormal projections and ringlike configurations. Sizeable areas of the neuronal soma are now denuded of satellite cells; underlying these areas, nerve processes are found abnormally invaginated into the neuronal cytoplasm. By the 14th day following irradiation, most neurons display marked degenerative changes including extensive regions of ribosome depletion, sequestration, vacuolization, autolysis, and, in some areas, swirls of filaments, myelin figures, and heterogeneous dense bodies. These observations demonstrate that X-irradiation produces profound cytopathological changes in nervous tissue isolated from the host and that many of these changes resemble the effects of radiation on nervous tissue in vivo. PMID:10976234

  12. The Mechanisms of Movement Control and Time Estimation in Cervical Dystonia Patients

    PubMed Central

    Lungu, Ovidiu V.; Shaw, Daniel J.; Kasparek, Tomas; Bareš, Martin

    2013-01-01

    Traditionally, the pathophysiology of cervical dystonia has been regarded mainly in relation to neurochemical abnormities in the basal ganglia. Recently, however, substantial evidence has emerged for cerebellar involvement. While the absence of neurological “cerebellar signs” in most dystonia patients may be considered at least provoking, there are more subtle indications of cerebellar dysfunction in complex, demanding tasks. Specifically, given the role of the cerebellum in the neural representation of time, in the millisecond range, dysfunction to this structure is considered to be of greater importance than dysfunction of the basal ganglia. In the current study, we investigated the performance of cervical dystonia patients on a computer task known to engage the cerebellum, namely, the interception of a moving target with changing parameters (speed, acceleration, and angle) with a simple response (pushing a button). The cervical dystonia patients achieved significantly worse results than a sample of healthy controls. Our results suggest that the cervical dystonia patients are impaired at integrating incoming visual information with motor responses during the prediction of upcoming actions, an impairment we interpret as evidence of cerebellar dysfunction. PMID:24198973

  13. Modeling neural circuits in Parkinson's disease.

    PubMed

    Psiha, Maria; Vlamos, Panayiotis

    2015-01-01

    Parkinson's disease (PD) is caused by abnormal neural activity of the basal ganglia which are connected to the cerebral cortex in the brain surface through complex neural circuits. For a better understanding of the pathophysiological mechanisms of PD, it is important to identify the underlying PD neural circuits, and to pinpoint the precise nature of the crucial aberrations in these circuits. In this paper, the general architecture of a hybrid Multilayer Perceptron (MLP) network for modeling the neural circuits in PD is presented. The main idea of the proposed approach is to divide the parkinsonian neural circuitry system into three discrete subsystems: the external stimuli subsystem, the life-threatening events subsystem, and the basal ganglia subsystem. The proposed model, which includes the key roles of brain neural circuit in PD, is based on both feed-back and feed-forward neural networks. Specifically, a three-layer MLP neural network with feedback in the second layer was designed. The feedback in the second layer of this model simulates the dopamine modulatory effect of compacta on striatum.

  14. A Dynamic Circuit Hypothesis for the Pathogenesis of Blepharospasm.

    PubMed

    Peterson, David A; Sejnowski, Terrence J

    2017-01-01

    Blepharospasm (sometimes called "benign essential blepharospasm," BEB) is one of the most common focal dystonias. It involves involuntary eyelid spasms, eye closure, and increased blinking. Despite the success of botulinum toxin injections and, in some cases, pharmacologic or surgical interventions, BEB treatments are not completely efficacious and only symptomatic. We could develop principled strategies for preventing and reversing the disease if we knew the pathogenesis of primary BEB. The objective of this study was to develop a conceptual framework and dynamic circuit hypothesis for the pathogenesis of BEB. The framework extends our overarching theory for the multifactorial pathogenesis of focal dystonias (Peterson et al., 2010) to incorporate a two-hit rodent model specifically of BEB (Schicatano et al., 1997). We incorporate in the framework three features critical to cranial motor control: (1) the joint influence of motor cortical regions and direct descending projections from one of the basal ganglia output nuclei, the substantia nigra pars reticulata, on brainstem motor nuclei, (2) nested loops composed of the trigeminal blink reflex arc and the long sensorimotor loop from trigeminal nucleus through thalamus to somatosensory cortex back through basal ganglia to the same brainstem nuclei modulating the reflex arc, and (3) abnormalities in the basal ganglia dopamine system that provide a sensorimotor learning substrate which, when combined with patterns of increased blinking, leads to abnormal sensorimotor mappings manifest as BEB. The framework explains experimental data on the trigeminal reflex blink excitability (TRBE) from Schicatano et al. and makes predictions that can be tested in new experimental animal models based on emerging genetics in dystonia, including the recently characterized striatal-specific D1R dopamine transduction alterations caused by the GNAL mutation. More broadly, the model will provide a guide for future efforts to mechanistically

  15. A Dynamic Circuit Hypothesis for the Pathogenesis of Blepharospasm

    PubMed Central

    Peterson, David A.; Sejnowski, Terrence J.

    2017-01-01

    Blepharospasm (sometimes called “benign essential blepharospasm,” BEB) is one of the most common focal dystonias. It involves involuntary eyelid spasms, eye closure, and increased blinking. Despite the success of botulinum toxin injections and, in some cases, pharmacologic or surgical interventions, BEB treatments are not completely efficacious and only symptomatic. We could develop principled strategies for preventing and reversing the disease if we knew the pathogenesis of primary BEB. The objective of this study was to develop a conceptual framework and dynamic circuit hypothesis for the pathogenesis of BEB. The framework extends our overarching theory for the multifactorial pathogenesis of focal dystonias (Peterson et al., 2010) to incorporate a two-hit rodent model specifically of BEB (Schicatano et al., 1997). We incorporate in the framework three features critical to cranial motor control: (1) the joint influence of motor cortical regions and direct descending projections from one of the basal ganglia output nuclei, the substantia nigra pars reticulata, on brainstem motor nuclei, (2) nested loops composed of the trigeminal blink reflex arc and the long sensorimotor loop from trigeminal nucleus through thalamus to somatosensory cortex back through basal ganglia to the same brainstem nuclei modulating the reflex arc, and (3) abnormalities in the basal ganglia dopamine system that provide a sensorimotor learning substrate which, when combined with patterns of increased blinking, leads to abnormal sensorimotor mappings manifest as BEB. The framework explains experimental data on the trigeminal reflex blink excitability (TRBE) from Schicatano et al. and makes predictions that can be tested in new experimental animal models based on emerging genetics in dystonia, including the recently characterized striatal-specific D1R dopamine transduction alterations caused by the GNAL mutation. More broadly, the model will provide a guide for future efforts to

  16. Dopaminergic Balance between Reward Maximization and Policy Complexity

    PubMed Central

    Parush, Naama; Tishby, Naftali; Bergman, Hagai

    2011-01-01

    Previous reinforcement-learning models of the basal ganglia network have highlighted the role of dopamine in encoding the mismatch between prediction and reality. Far less attention has been paid to the computational goals and algorithms of the main-axis (actor). Here, we construct a top-down model of the basal ganglia with emphasis on the role of dopamine as both a reinforcement learning signal and as a pseudo-temperature signal controlling the general level of basal ganglia excitability and motor vigilance of the acting agent. We argue that the basal ganglia endow the thalamic-cortical networks with the optimal dynamic tradeoff between two constraints: minimizing the policy complexity (cost) and maximizing the expected future reward (gain). We show that this multi-dimensional optimization processes results in an experience-modulated version of the softmax behavioral policy. Thus, as in classical softmax behavioral policies, probability of actions are selected according to their estimated values and the pseudo-temperature, but in addition also vary according to the frequency of previous choices of these actions. We conclude that the computational goal of the basal ganglia is not to maximize cumulative (positive and negative) reward. Rather, the basal ganglia aim at optimization of independent gain and cost functions. Unlike previously suggested single-variable maximization processes, this multi-dimensional optimization process leads naturally to a softmax-like behavioral policy. We suggest that beyond its role in the modulation of the efficacy of the cortico-striatal synapses, dopamine directly affects striatal excitability and thus provides a pseudo-temperature signal that modulates the tradeoff between gain and cost. The resulting experience and dopamine modulated softmax policy can then serve as a theoretical framework to account for the broad range of behaviors and clinical states governed by the basal ganglia and dopamine systems. PMID:21603228

  17. Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement.

    PubMed

    Lipski, Witold J; Wozny, Thomas A; Alhourani, Ahmad; Kondylis, Efstathios D; Turner, Robert S; Crammond, Donald J; Richardson, Robert Mark

    2017-09-01

    Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also

  18. Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia

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

    Vafai, A.; Wellish, M.; Devlin, M.

    1988-04-01

    Lysates of radiolabeled explants from four human trigeminal ganglia were immunoprecipitated with antibodies to varicella-zoster virus (VZV) and to herpes simplex virus. Both herpes simplex virus- and VZV-specific proteins were detected in lysates of all four ganglia. Absence of reactivity in ganglion explants with monoclonal antibodies suggested that herpes simplex virus and VZV were not reactivated during the culture period. In situ hybridization studies demonstrated the presence of RNA transcripts from the VZV immediate early gene 63. This approach to the detection of herpes simplex virus and VZV expression in human ganglia should facilitate analysis of viral RNA and proteinsmore » in human sensory ganglia.« less

  19. Patterns of age related changes for phosphodiesterase type-10A in comparison with dopamine D2/3 receptors and sub-cortical volumes in the human basal ganglia: A PET study with 18F-MNI-659 and 11C-raclopride with correction for partial volume effect.

    PubMed

    Fazio, Patrik; Schain, Martin; Mrzljak, Ladislav; Amini, Nahid; Nag, Sangram; Al-Tawil, Nabil; Fitzer-Attas, Cheryl J; Bronzova, Juliana; Landwehrmeyer, Bernhard; Sampaio, Cristina; Halldin, Christer; Varrone, Andrea

    2017-05-15

    Phosphodiesterase 10A enzyme (PDE10A) is an important striatal target that has been shown to be affected in patients with neurodegenerative disorders, particularly Huntington´s disease (HD). PDE10A is expressed on striatal neurones in basal ganglia where other known molecular targets are enriched such as dopamine D 2/3 receptors (D 2/3 R). The aim of this study was to examine the availability of PDE10A enzyme in relation with age and gender and to compare those changes with those related to D 2/3 R and volumes in different regions of the basal ganglia. As a secondary objective we examined the relative distribution of D 2/3 R and PDE10A enzyme in the striatum and globus pallidus. Forty control subjects (20F/20M; age: 44±11y, age range 27-69) from an ongoing positron emission tomography (PET) study in HD gene expansion carriers were included. Subjects were examined with PET using the high-resolution research tomograph (HRRT) and with 3T magnetic resonance imaging (MRI). The PDE10A radioligand 18 F-MNI-659 and D 2/3 R radioligand 11 C-raclopride were used. The outcome measure was the binding potential (BP ND ) estimated with the two-tissue compartment model ( 18 F-MNI-659) and the simplified reference tissue model ( 11 C-raclopride) using the cerebellum as reference region. The PET data were corrected for partial volume effects. In the striatum, PDE10A availability showed a significant age-related decline that was larger compared to the age-related decline of D 2/3 R availability and to the age-related decline of volumes measured with MRI. In the globus pallidus, a less pronounced decline of PDE10A availability was observed, whereas D 2/3 R availability and volumes seemed to be rather stable with aging. The distribution of the PDE10A enzyme was different from the distribution of D 2/3 R, with higher availability in the globus pallidus. These results indicate that aging is associated with a considerable physiological reduction of the availability of PDE10A enzyme in

  20. The subdiaphragmatic part of the phrenic nerve - morphometry and connections to autonomic ganglia.

    PubMed

    Loukas, Marios; Du Plessis, Maira; Louis, Robert G; Tubbs, R Shane; Wartmann, Christopher T; Apaydin, Nihal

    2016-01-01

    Few anatomical textbooks offer much information concerning the anatomy and distribution of the phrenic nerve inferior to the diaphragm. The aim of this study was to identify the subdiaphragmatic distribution of the phrenic nerve, the presence of phrenic ganglia, and possible connections to the celiac plexus. One hundred and thirty formalin-fixed adult cadavers were studied. The right phrenic nerve was found inferior to the diaphragm in 98% with 49.1% displaying a right phrenic ganglion. In 22.8% there was an additional smaller ganglion (right accessory phrenic ganglion). The remaining 50.9% had no grossly identifiable right phrenic ganglion. Most (65.5% of specimens) exhibited plexiform communications with the celiac ganglion, aorticorenal ganglion, and suprarenal gland. The left phrenic nerve inferior to the diaphragm was observed in 60% of specimens with 19% containing a left phrenic ganglion. No accessory left phrenic ganglia were observed. The left phrenic ganglion exhibited plexiform communications to several ganglia in 71.4% of specimens. Histologically, the right phrenic and left phrenic ganglia contained large soma concentrated in their peripheries. Both phrenic nerves and ganglia were closely related to the diaphragmatic crura. Surgically, sutures to approximate the crura for repair of hiatal hernias must be placed above the ganglia in order to avoid iatrogenic injuries to the autonomic supply to the diaphragm and abdomen. These findings could also provide a better understanding of the anatomy and distribution of the fibers of that autonomic supply. © 2015 Wiley Periodicals, Inc.

  1. Inhibiting the Hedgehog Pathway in Patients with the Basal-Cell Nevus Syndrome

    PubMed Central

    Tang, Jean Y.; Mackay-Wiggan, Julian M.; Aszterbaum, Michelle; Yauch, Robert L.; Lindgren, Joselyn; Chang, Kris; Coppola, Carol; Chanana, Anita M.; Marji, Jackleen; Bickers, David R.; Epstein, Ervin H.

    2012-01-01

    BACKGROUND Dysregulated hedgehog signaling is the pivotal molecular abnormality underlying basal-cell carcinomas. Vismodegib is a new orally administered hedgehog-pathway inhibitor that produces objective responses in locally advanced and metastatic basal-cell carcinomas. METHODS We tested the anti–basal-cell carcinoma efficacy of vismodegib in a randomized, double-blind, placebo-controlled trial in patients with the basal-cell nevus syndrome at three clinical centers from September 2009 through January 2011. The primary end point was reduction in the incidence of new basal-cell carcinomas that were eligible for surgical resection (surgically eligible) with vismodegib versus placebo after 3 months; secondary end points included reduction in the size of existing basal-cell carcinomas. RESULTS In 41 patients followed for a mean of 8 months (range, 1 to 15) after enrollment, the per-patient rate of new surgically eligible basal-cell carcinomas was lower with vismodegib than with placebo (2 vs. 29 cases per group per year, P<0.001), as was the size (percent change from baseline in the sum of the longest diameter) of existing clinically significant basal-cell carcinomas (−65% vs. −11%, P = 0.003). In some patients, all basal-cell carcinomas clinically regressed. No tumors progressed during treatment with vismodegib. Patients receiving vismodegib routinely had grade 1 or 2 adverse events of loss of taste, muscle cramps, hair loss, and weight loss. Overall, 54% of patients (14 of 26) receiving vismodegib discontinued drug treatment owing to adverse events. At 1 month, vismodegib use had reduced the hedgehog target-gene expression by basal-cell carcinoma by 90% (P<0.001) and diminished tumor-cell proliferation, but apoptosis was not affected. No residual basal-cell carcinoma was detectable in 83% of biopsy samples taken from sites of clinically regressed basal-cell carcinomas. CONCLUSIONS Vismodegib reduces the basal-cell carcinoma tumor burden and blocks growth of

  2. Application research of Ganglia in Hadoop monitoring and management

    NASA Astrophysics Data System (ADS)

    Li, Gang; Ding, Jing; Zhou, Lixia; Yang, Yi; Liu, Lei; Wang, Xiaolei

    2017-03-01

    There are many applications of Hadoop System in the field of large data, cloud computing. The test bench of storage and application in seismic network at Earthquake Administration of Tianjin use with Hadoop system, which is used the open source software of Ganglia to operate and monitor. This paper reviews the function, installation and configuration process, application effect of operating and monitoring in Hadoop system of the Ganglia system. It briefly introduces the idea and effect of Nagios software monitoring Hadoop system. It is valuable for the industry in the monitoring system of cloud computing platform.

  3. Long term effects of lipopolysaccharide on satellite glial cells in mouse dorsal root ganglia

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

    Blum, E.; Procacci, P.; Conte, V.

    Lipopolysaccharide (LPS) has been used extensively to study neuroinflammation, but usually its effects were examined acutely (24 h<). We have shown previously that a single intraperitoneal LPS injection activated satellite glial cells (SGCs) in mouse dorsal root ganglia (DRG) and altered several functional parameters in these cells for at least one week. Here we asked whether the LPS effects would persist for 1 month. We injected mice with a single LPS dose and tested pain behavior, assessed SGCs activation in DRG using glial fibrillary acidic protein (GFAP) immunostaining, and injected a fluorescent dye intracellularly to study intercellular coupling. Electron microscopymore » was used to quantitate changes in gap junctions. We found that at 30 days post-LPS the threshold to mechanical stimulation was lower than in controls. GFAP expression, as well as the magnitude of dye coupling among SGCs were greater than in controls. Electron microscopy analysis supported these results, showing a greater number of gap junctions and an abnormal growth of SGC processes. These changes were significant, but less prominent than at 7 days post-LPS. We conclude that a single LPS injection exerts long-term behavioral and cellular changes. The results are consistent with the idea that SGC activation contributes to hyperalgesia. - Highlights: • A single lipopolysaccharides injection activated glia in mouse dorsal root ganglia for 30 days. • This was accompanied by increased communications by gap junctions among glia and by hyperalgesia. • Glial activation and coupling may contribute to chronic pain.« less

  4. CONTRAST BETWEEN OSMIUM-FIXED AND PERMANGANATE-FIXED TOAD SPINAL GANGLIA

    PubMed Central

    Rosenbluth, Jack

    1963-01-01

    Chains of vesicles are prominent near the plasma membranes of both the neurons and satellite cells of osmium-fixed toad spinal ganglia. In permanganate-fixed specimens, however, such vesicles are absent, and in their place are continuous invaginations of the plasma membranes of these cells. The discrepancy suggests that the serried vesicles seen in osmium-fixed preparations arise through disintegration of plasma membrane invaginations, and do not represent active pinocytosis, as has been suggested previously. A second difference between ganglia fixed by these two methods is that rows of small, disconnected cytoplasmic globules occur in the sheaths of permanganate-fixed ganglia, but not in osmium-fixed samples. It is suggested that these globules arise from the breakdown of thin sheets of satellite cell cytoplasm which occur as continuous lamellae in osmium-fixed specimens. Possible mechanisms of these membrane reorganizations, and the relevance of these findings to other tissues, are discussed. PMID:13990905

  5. Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders

    PubMed Central

    Brimberg, Lior; Benhar, Itai; Mascaro-Blanco, Adita; Alvarez, Kathy; Lotan, Dafna; Winter, Christine; Klein, Julia; Moses, Allon E; Somnier, Finn E; Leckman, James F; Swedo, Susan E; Cunningham, Madeleine W; Joel, Daphna

    2012-01-01

    Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders. PMID:22534626

  6. Neurologic manifestations in welders with pallidal MRI T1 hyperintensity.

    PubMed

    Josephs, K A; Ahlskog, J E; Klos, K J; Kumar, N; Fealey, R D; Trenerry, M R; Cowl, C T

    2005-06-28

    Neurologic symptoms have been attributed to manganese fumes generated during welding. Increased T1 MRI signal in the basal ganglia is a biologic marker of manganese accumulation. Recent studies have associated welding and parkinsonism, but generally without MRI corroboration. To characterize the clinical and neuropsychological features of patients with MRI basal ganglia T1 hyperintensity, who were ultimately diagnosed with neurotoxicity from welding fumes. The medical records of welders referred to the Department of Neurology with neurologic problems and basal ganglia T1 hyperintensity were reviewed. All eight patients were male career welders with increased T1 basal ganglia signal on MRI of the brain. Several different clinical syndromes were recognized: a parkinsonian syndrome (three patients), a syndrome of multifocal myoclonus and limited cognitive impairment (two patients), a mixed syndrome with vestibular-auditory dysfunction (two patients), and minor subjective cognitive impairment, anxiety, and sleep apnea (one patient). Neuropsychometric testing suggested subcortical or frontal involvement. Inadequate ventilation or lack of personal respiratory protection during welding was a common theme. Welding without proper protection was associated with syndromes of parkinsonism, multifocal myoclonus, mild cognitive impairment, and vestibular-auditory dysfunction. The MRI T1 hyperintensity in the basal ganglia suggests that these may have been caused by manganese neurotoxicity.

  7. Maintenance of basal levels of autophagy in Huntington's disease mouse models displaying metabolic dysfunction.

    PubMed

    Baldo, Barbara; Soylu, Rana; Petersén, Asa

    2013-01-01

    Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in the huntingtin protein. Neuropathology in the basal ganglia and in the cerebral cortex has been linked to the motor and cognitive symptoms whereas recent work has suggested that the hypothalamus might be involved in the metabolic dysfunction. Several mouse models of HD that display metabolic dysfunction have hypothalamic pathology, and expression of mutant huntingtin in the hypothalamus has been causally linked to the development of metabolic dysfunction in mice. Although the pathogenic mechanisms by which mutant huntingtin exerts its toxic functions in the HD brain are not fully known, several studies have implicated a role for the lysososomal degradation pathway of autophagy. Interestingly, changes in autophagy in the hypothalamus have been associated with the development of metabolic dysfunction in wild-type mice. We hypothesized that expression of mutant huntingtin might lead to changes in the autophagy pathway in the hypothalamus in mice with metabolic dysfunction. We therefore investigated whether there were changes in basal levels of autophagy in a mouse model expressing a fragment of 853 amino acids of mutant huntingtin selectively in the hypothalamus using a recombinant adeno-associate viral vector approach as well as in the transgenic BACHD mice. We performed qRT-PCR and Western blot to investigate the mRNA and protein expression levels of selected autophagy markers. Our results show that basal levels of autophagy are maintained in the hypothalamus despite the presence of metabolic dysfunction in both mouse models. Furthermore, although there were no major changes in autophagy in the striatum and cortex of BACHD mice, we detected modest, but significant differences in levels of some markers in mice at 12 months of age. Taken together, our results indicate that overexpression of mutant huntingtin in mice do not significantly perturb basal levels of

  8. Changes in nuclear morphology and chromatin texture of basal keratinocytes in melasma.

    PubMed

    Brianezi, G; Handel, A C; Schmitt, J V; Miot, L D B; Miot, H A

    2015-04-01

    The pathogenesis of melasma and the role of keratinocytes in disease development and maintenance are not completely understood. Dermal abnormalities, the expression of inflammatory mediators, growth factors, epithelial expression of melanocortin and sexual hormones receptors suggest that not only melanocytes, but entire epidermal melanin unit is involved in melasma physiopathology. To compare nuclear morphological features and chromatin texture between basal keratinocytes in facial melasma and adjacent normal skin. We took facial skin biopsies (2 mm melasma and adjacent normal skin) from women processed for haematoxylin and eosin. Thirty non-overlapping basal keratinocyte nuclei were segmented and descriptors of area, highest diameter, perimeter, circularity, pixel intensity, profilometric index (Ra) and fractal dimension were extracted using ImageJ software. Basal keratinocyte nuclei from facial melasma epidermis displayed larger size, irregular shape, hyperpigmentation and chromatin heterogeneity by fractal dimension than perilesional skin. Basal keratinocytes from facial melasma display changes in nuclear form and chromatin texture, suggesting that the phenotype differences between melasma and adjacent facial skin can result from complete epidermal melanin unit alterations, not just hypertrophic melanocytes. © 2014 European Academy of Dermatology and Venereology.

  9. Anatomy of the nerves and ganglia of the aortic plexus in males

    PubMed Central

    Beveridge, Tyler S; Johnson, Marjorie; Power, Adam; Power, Nicholas E; Allman, Brian L

    2015-01-01

    It is well accepted that the aortic plexus is a network of pre- and post-ganglionic nerves overlying the abdominal aorta, which is primarily involved with the sympathetic innervation to the mesenteric, pelvic and urogenital organs. Because a comprehensive anatomical description of the aortic plexus and its connections with adjacent plexuses are lacking, these delicate structures are prone to unintended damage during abdominal surgeries. Through dissection of fresh, frozen human cadavers (n = 7), the present study aimed to provide the first complete mapping of the nerves and ganglia of the aortic plexus in males. Using standard histochemical procedures, ganglia of the aortic plexus were verified through microscopic analysis using haematoxylin & eosin (H&E) and anti-tyrosine hydroxylase stains. All specimens exhibited four distinct sympathetic ganglia within the aortic plexus: the right and left spermatic ganglia, the inferior mesenteric ganglion and one previously unidentified ganglion, which has been named the prehypogastric ganglion by the authors. The spermatic ganglia were consistently supplied by the L1 lumbar splanchnic nerves and the inferior mesenteric ganglion and the newly characterized prehypogastric ganglion were supplied by the left and right L2 lumbar splanchnic nerves, respectively. Additionally, our examination revealed the aortic plexus does have potential for variation, primarily in the possibility of exhibiting accessory splanchnic nerves. Clinically, our results could have significant implications for preserving fertility in men as well as sympathetic function to the hindgut and pelvis during retroperitoneal surgeries. PMID:25382240

  10. Uncovering the Forgotten Effect of Superior Cervical Ganglia on Pupil Diameter in Subarachnoid Hemorrhage: An Experimental Study.

    PubMed

    Onen, Mehmet Resid; Yilmaz, Ilhan; Ramazanoglu, Leyla; Aydin, Mehmet Dumlu; Keles, Sadullah; Baykal, Orhan; Aydin, Nazan; Gundogdu, Cemal

    2018-01-01

    To investigate the relationship between neuron density of the superior cervical sympathetic ganglia and pupil diameter in subarachnoid hemorrhage. This study was conducted on 22 rabbits; 5 for the baseline control group, 5 for the SHAM group and 12 for the study group. Pupil diameters were measured via sunlight and ocular tomography on day 1 as the control values. Pupil diameters were re-measured after injecting 0.5 cc saline to the SHAM group, and autologous arterial blood into the cisterna magna of the study group. After 3 weeks, the brain, superior cervical sympathetic ganglia and ciliary ganglia were extracted with peripheral tissues bilaterally and examined histopathologically. Pupil diameters were compared with neuron densities of the sympathetic ganglia and ciliary ganglia which were examined using stereological methods. Baseline values were; normal pupil diameter 7.180±620 ?m and mean neuron density of the superior cervical sympathetic ganglia 6.321±510/mm3, degenerated neuron density of ciliary ganglia was 5±2/mm3 after histopathological examination in the control group. These values were measured as 6.850±578 ?m, 5.950±340/mm3 and 123±39/mm3 in the SHAM group and 9.910±840 ?m, 7.950±764/mm3 and 650±98/mm3 in the study group. A linear relationship was determined between neuron density of the superior cervical sympathetic ganglia and pupil diameters (p < 0.005). Degenerated ciliary ganglia neuron density had an inverse effect on pupil diameters in all groups (p < 0.0001). Highly degenerated neuron density of the ciliary ganglion is not responsible for pupil dilatation owing to parasympathetic pupilloconstrictor palsy, but high neuron density of the pupillodilatatory superior cervical sympathetic ganglia should be considered an important factor for pupil dilatation.

  11. Increasing Dopamine Levels in the Brain Improves Feedback-Based Procedural Learning in Healthy Participants: An Artificial-Grammar-Learning Experiment

    ERIC Educational Resources Information Center

    de Vries, Meinou H.; Ulte, Catrin; Zwitserlood, Pienie; Szymanski, Barbara; Knecht, Stefan

    2010-01-01

    Recently, an increasing number of studies have suggested a role for the basal ganglia and related dopamine inputs in procedural learning, specifically when learning occurs through trial-by-trial feedback (Shohamy, Myers, Kalanithi, & Gluck. (2008). "Basal ganglia and dopamine contributions to probabilistic category learning." "Neuroscience and…

  12. Could quantitative longitudinal peak systolic strain help in the detection of left ventricular wall motion abnormalities in our daily echocardiographic practice?

    PubMed

    Benyounes, Nadia; Lang, Sylvie; Gout, Olivier; Ancédy, Yann; Etienney, Arnaud; Cohen, Ariel

    2016-10-01

    Transthoracic echocardiography is the most commonly used tool for the detection of left ventricular wall motion (LVWM) abnormalities using "naked eye evaluation". This subjective and operator-dependent technique requires a high level of clinical training and experience. Two-dimensional speckle-tracking echocardiography (2D-STE), which is less operator-dependent, has been proposed for this purpose. However, the role of on-line segmental longitudinal peak systolic strain (LPSS) values in the prediction of LVWM has not been fully evaluated. To test segmental LPSS for predicting LVWM abnormalities in routine echocardiography laboratory practice. LVWM was evaluated by an experienced cardiologist, during routine practice, in 620 patients; segmental LPSS values were then calculated. In this work, reflecting real life, 99.6% of segments were successfully tracked. Mean (95% confidence interval [CI]) segmental LPSS values for normal basal (n=3409), mid (n=3468) and apical (n=3466) segments were -16.7% (-16.9% to -16.5%), -18.2% (-18.3% to -18.0%) and -21.1% (-21.3% to -20.9%), respectively. Mean (95% CI) segmental LPSS values for hypokinetic basal (n=114), mid (n=116) and apical (n=90) segments were -7.7% (-9.0% to -6.3%), -10.1% (-11.1% to -9.0%) and -9.3% (-10.5% to -8.1%), respectively. Mean (95% CI) segmental LPSS values for akinetic basal (n=128), mid (n=95) and apical (n=91) segments were -6.6% (-8.0% to -5.1%), -6.1% (-7.7% to -4.6%) and -4.2% (-5.4% to -3.0%), respectively. LPSS allowed the differentiation between normal and abnormal segments at basal, mid and apical levels. An LPSS value≥-12% detected abnormal segmental motion with a sensitivity of 78% for basal, 70% for mid and 82% for apical segments. Segmental LPSS values may help to differentiate between normal and abnormal left ventricular segments. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Abnormalities in the basement membrane structure promote basal keratinocytes in the epidermis of hypertrophic scars to adopt a proliferative phenotype.

    PubMed

    Yang, Shaowei; Sun, Yexiao; Geng, Zhijun; Ma, Kui; Sun, Xiaoyan; Fu, Xiaobing

    2016-05-01

    The majority of studies on scar formation have mainly focused on the dermis and little is known of the involvement of the epidermis. Previous research has demonstrated that the scar tissue-derived keratinocytes are different from normal cells at both the genetic and cell biological levels; however, the mechanisms responsible for the fundamental abnormalities in keratinocytes during scar development remain elusive. For this purpose, in this study, we used normal, wound edge and hypertrophic scar tissue to examine the morphological changes which occur during epidermal regeneration as part of the wound healing process and found that the histological structure of hypertrophic scar tissues differed from that of normal skin, with a significant increase in epidermal thickness. Notably, staining of the basement membrane (BM) appeared to be absent in the scar tissues. Moreover, immunofluorescence staining for cytokeratin (CK)10, CK14, CK5, CK19 and integrin-β1 indicated the differential expression of cell markers in the epidermal keratinocytes among the normal, wound edge and hypertrophic scar tissues, which corresponded with the altered BM structures. By using a panel of proteins associated with BM components, we validated our hypothesis that the BM plays a significant role in regulating the cell fate decision of epidermal keratinocytes during skin wound healing. Alterations in the structure of the BM promote basal keratinocytes to adopt a proliferative phenotype both in vivo and in vitro.

  14. Dramatic Effects of Speech Task on Motor and Linguistic Planning in Severely Dysfluent Parkinsonian Speech

    ERIC Educational Resources Information Center

    Van Lancker Sidtis, Diana; Cameron, Krista; Sidtis, John J.

    2012-01-01

    In motor speech disorders, dysarthric features impacting intelligibility, articulation, fluency and voice emerge more saliently in conversation than in repetition, reading or singing. A role of the basal ganglia in these task discrepancies has been identified. Further, more recent studies of naturalistic speech in basal ganglia dysfunction have…

  15. Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders

    PubMed Central

    Iriki, Atsushi; Isoda, Masaki

    2015-01-01

    Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles. PMID:26180116

  16. Neurotransmitter activity is linked to outcome following subthalamic deep brain stimulation in Parkinson's disease.

    PubMed

    O'Gorman Tuura, Ruth L; Baumann, Christian R; Baumann-Vogel, Heide

    2018-05-01

    While the mechanisms underlying the therapeutic effects of deep brain stimulation (DBS) in Parkinson's Disease (PD) are not yet fully understood, DBS appears to exert a wide range of neurochemical effects on the network level, thought to arise from activation of inhibitory and excitatory pathways. The activity within the primary inhibitory (GABAergic) and excitatory (glutamatergic) neurotransmitter systems may therefore play an important role in the therapeutic efficacy of DBS in PD. The purpose of this study was to investigate abnormalities in GABA-ergic and glutamatergic neurotransmission in PD, and to examine the link between neurotransmitter levels and outcome following DBS. Magnetic resonance spectra were acquired from the pons and basal ganglia in sixteen patients with PD and sixteen matched control participants. GABA and glutamate levels were quantified with LCModel, an automated spectral fitting package. Fourteen patients subsequently underwent DBS, and PD symptoms were evaluated with the MDS-UPDRS at baseline and six months after surgery. The efficacy of DBS treatment was evaluated from the percentage improvement in MDS-UPDRS scores. Basal ganglia GABA levels were significantly higher in PD patients relative to control participants (p < 0.01), while pontine glutamate + glutamine (Glx) levels were significantly lower in patients with PD (p < 0.05). While GABA levels were not significantly related to outcome post-surgery, basal ganglia glutamate levels emerged as a significant predictor of outcome, suggesting a possible role for glutamatergic neurotransmission in the therapeutic mechanism of DBS. GABAergic and glutamatergic neurotransmission is altered in PD, and glutamatergic activity in particular may influence outcome post-surgery. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Brain structural differences associated with the behavioural phenotype in children with Williams syndrome.

    PubMed

    Campbell, Linda E; Daly, Eileen; Toal, Fiona; Stevens, Angela; Azuma, Rayna; Karmiloff-Smith, Annette; Murphy, Declan G M; Murphy, Kieran C

    2009-03-03

    We investigated structural brain morphology of intellectually disabled children with Williams (WS) syndrome and its relationship to the behavioural phenotype. We compared the neuroanatomy of 15 children (mean age:13+/-2) with WS and 15 age/gender-matched healthy children using a manual region-of-interest analysis to measure bulk (white+grey) tissue volumes and unbiased fully-automated voxel-based morphometry to assess differences in grey/white matter throughout the brain. Ratings of abnormal behaviours were correlated with brain structure. Compared to controls, the brains of children with WS had a decreased volume of the right parieto-occipital regions and basal ganglia. We identified reductions of grey matter of the parieto-occipital regions, left putamen/globus pallidus and thalamus; and in white matter of the basal ganglia and right posterior cingulate gyrus. In contrast, significant increases of grey matter were identified in the frontal lobes, anterior cingulate gyrus, left temporal lobe, and of white matter bilaterally in the anterior cingulate. Inattention in WS was correlated with volumetric differences in the frontal lobes, caudate nucleus and cerebellum, and hyperactivity was related to differences in the left temporal and parietal lobes and cerebellum. Finally, ratings of peer problems were related to differences in the temporal lobes, right basal ganglia and frontal lobe. In one of the first studies of brain structure in intellectually disabled children with WS using voxel-based morphometry, our findings suggest that this group has specific differences in grey/white matter morphology. In addition, it was found that structural differences were correlated to ratings of inattention, hyperactivity and peer problems in children with WS.

  18. Mutations in SURF1 are important genetic causes of Leigh syndrome in Slovak patients.

    PubMed

    Danis, Daniel; Brennerova, Katarina; Skopkova, Martina; Kurdiova, Timea; Ukropec, Jozef; Stanik, Juraj; Kolnikova, Miriam; Gasperikova, Daniela

    2018-04-01

    Leigh syndrome is a progressive early onset neurodegenerative disease typically presenting with psychomotor regression, signs of brainstem and/or basal ganglia disease, lactic acidosis, and characteristic magnetic resonance imaging findings. At molecular level, deficiency of respiratory complexes and/or pyruvate dehydrogenase complex is usually observed. Nuclear gene SURF1 encodes an assembly factor for cytochrome c-oxidase complex of the respiratory chain and autosomal recessive mutations in SURF1 are one of the most frequent causes of cytochrome c-oxidase-related Leigh syndrome cases. Here, we aimed to elucidate the genetic basis of Leigh syndrome in three Slovak families. Three probands presenting with Leigh syndrome were selected for DNA analysis. The first proband, presenting with atypical LS onset without abnormal basal ganglia magnetic resonance imaging findings, was analyzed with whole exome sequencing. In the two remaining probands, SURF1 was screened by Sanger sequencing. Four different heterozygous mutations were identified in SURF1: c.312_321delinsAT:p.(Pro104Profs*1), c.588+1G>A, c.823_833+7del:p. (?) and c.845_846del:p.(Ser282Cysfs*9). All the mutations are predicted to have a loss-of-function effect. We identified disease-causing mutations in all three probands, which points to the important role of SURF1 gene in etiology of Leigh syndrome in Slovakia. Our data showed that patients with atypical Leigh syndrome phenotype without lesions in basal ganglia may benefit from the whole exome sequencing method. In the case of probands presenting the typical phenotype, Sanger sequencing of the SURF1 gene seems to be an effective method of DNA analysis.

  19. Transcriptome analysis of trigeminal ganglia following masseter muscle inflammation in rats

    PubMed Central

    Park, Jennifer; Asgar, Jamila; Ro, Jin Y.

    2016-01-01

    Background Chronic pain in masticatory muscles is a major medical problem. Although mechanisms underlying persistent pain in masticatory muscles are not fully understood, sensitization of nociceptive primary afferents following muscle inflammation or injury contributes to muscle hyperalgesia. It is well known that craniofacial muscle injury or inflammation induces regulation of multiple genes in trigeminal ganglia, which is associated with muscle hyperalgesia. However, overall transcriptional profiles within trigeminal ganglia following masseter inflammation have not yet been determined. In the present study, we performed RNA sequencing assay in rat trigeminal ganglia to identify transcriptome profiles of genes relevant to hyperalgesia following inflammation of the rat masseter muscle. Results Masseter inflammation differentially regulated >3500 genes in trigeminal ganglia. Predominant biological pathways were predicted to be related with activation of resident non-neuronal cells within trigeminal ganglia or recruitment of immune cells. To focus our analysis on the genes more relevant to nociceptors, we selected genes implicated in pain mechanisms, genes enriched in small- to medium-sized sensory neurons, and genes enriched in TRPV1-lineage nociceptors. Among the 2320 candidate genes, 622 genes showed differential expression following masseter inflammation. When the analysis was limited to these candidate genes, pathways related with G protein-coupled signaling and synaptic plasticity were predicted to be enriched. Inspection of individual gene expression changes confirmed the transcriptional changes of multiple nociceptor genes associated with masseter hyperalgesia (e.g., Trpv1, Trpa1, P2rx3, Tac1, and Bdnf) and also suggested a number of novel probable contributors (e.g., Piezo2, Tmem100, and Hdac9). Conclusion These findings should further advance our understanding of peripheral mechanisms involved in persistent craniofacial muscle pain conditions and provide a

  20. [Lesions in the pars compacta substantiae nigra and the subthalamic nucleus modify the density of muscarinic receptors in different nuclei of the basal ganglia].

    PubMed

    Blanco-Lezcano, L; Rocha-Arrieta, L L; Martínez-Martí, L; Alvarez-González, L; Pavón-Fuentes, N; Macías-González, R; Serrano-Sánchez, T; Rosillo-Martí, J C; Coro-Grave de Peralta, Y; Bauza-Calderín, Y; Briones, M

    Several studies that has focused to the dopaminergic transmission in the basal ganglia in parkinsonian condition, but only a few article has taking into account the imbalance between dopaminergic and cholinergic transmission. To evaluate the muscarinic cholinergic receptors density in SNc and PPN in the 6-OHDA model. Were organized five experimental groups in correspondence to the place of the lesion: I. Non treated rats, II. 6-OHDA lesion in SNc, III. 6-OHDA lesion in SNc + quinolinic acid lesion in NST, IV. Sham operated rats, V. Quinolinic acid in STN. Were obtained coronal sections of 20 microm thickness of SNc and PPN from rats and in these sections was evaluated the muscarinic receptors density through autoradiographic technique with [3H]quinuclidinylbenzilate (QNB) (1.23 nM). The muscarinic antagonist atropine (1 microM) was utilized as non-specific union. The density was evaluated in both hemispheres and the density optical was converted in fentomolas/mg of tissue with base to values obtained from tritium standards. Significant diminution of the muscarinic receptors density was found in the SNc ipsilateral to the 6-OHDA lesion from experimental groups II (t=2.76; p<0.05) and III (t=4.06; p<0.05). In the group V, was seen a significant increase of muscarinic receptor density in the SNc ipsilateral to the 6-OHDA lesion. The comparison between experimental groups evidenced significant differences among them (F=13.13; p<0.001) with a significant decrease in the density from SNc of groups II and III and significant increase in the density from SNc of group V in comparison of the others groups. In relation to PPN, muscarinic receptors density from right PPN ipsilateral to the 6-OHDA lesion, shown significant differences (F=3.93; p<0.01) between the experimental groups with a significant increase of this variable in the group II. These results signal a modification of cholinergic activity after 6-OHDA lesion. The changes in the muscarinic receptors populations