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Sample records for basal ganglia function

  1. Striatal plasticity and basal ganglia circuit function.

    PubMed

    Kreitzer, Anatol C; Malenka, Robert C

    2008-11-26

    The dorsal striatum, which consists of the caudate and putamen, is the gateway to the basal ganglia. It receives convergent excitatory afferents from cortex and thalamus and forms the origin of the direct and indirect pathways, which are distinct basal ganglia circuits involved in motor control. It is also a major site of activity-dependent synaptic plasticity. Striatal plasticity alters the transfer of information throughout basal ganglia circuits and may represent a key neural substrate for adaptive motor control and procedural memory. Here, we review current understanding of synaptic plasticity in the striatum and its role in the physiology and pathophysiology of basal ganglia function. PMID:19038213

  2. Functional Neuroanatomy of the Basal Ganglia

    PubMed Central

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

    2012-01-01

    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. PMID:23071379

  3. Reward functions of the basal ganglia.

    PubMed

    Schultz, Wolfram

    2016-07-01

    Besides their fundamental movement function evidenced by Parkinsonian deficits, the basal ganglia are involved in processing closely linked non-motor, cognitive and reward information. This review describes the reward functions of three brain structures that are major components of the basal ganglia or are closely associated with the basal ganglia, namely midbrain dopamine neurons, pedunculopontine nucleus, and striatum (caudate nucleus, putamen, nucleus accumbens). Rewards are involved in learning (positive reinforcement), approach behavior, economic choices and positive emotions. The response of dopamine neurons to rewards consists of an early detection component and a subsequent reward component that reflects a prediction error in economic utility, but is unrelated to movement. Dopamine activations to non-rewarded or aversive stimuli reflect physical impact, but not punishment. Neurons in pedunculopontine nucleus project their axons to dopamine neurons and process sensory stimuli, movements and rewards and reward-predicting stimuli without coding outright reward prediction errors. Neurons in striatum, besides their pronounced movement relationships, process rewards irrespective of sensory and motor aspects, integrate reward information into movement activity, code the reward value of individual actions, change their reward-related activity during learning, and code own reward in social situations depending on whose action produces the reward. These data demonstrate a variety of well-characterized reward processes in specific basal ganglia nuclei consistent with an important function in non-motor aspects of motivated behavior. PMID:26838982

  4. Functional anatomy of thalamus and basal ganglia.

    PubMed

    Herrero, María-Trinidad; Barcia, Carlos; Navarro, Juana Mari

    2002-08-01

    THALAMUS: The human thalamus is a nuclear complex located in the diencephalon and comprising of four parts (the hypothalamus, the epythalamus, the ventral thalamus, and the dorsal thalamus). The thalamus is a relay centre subserving both sensory and motor mechanisms. Thalamic nuclei (50-60 nuclei) project to one or a few well-defined cortical areas. Multiple cortical areas receive afferents from a single thalamic nucleus and send back information to different thalamic nuclei. The corticofugal projection provides positive feedback to the "correct" input, while at the same time suppressing irrelevant information. Topographical organisation of the thalamic afferents and efferents is contralateral, and the lateralisation of the thalamic functions affects both sensory and motoric aspects. Symptoms of lesions located in the thalamus are closely related to the function of the areas involved. An infarction or haemorrhage thalamic lesion can develop somatosensory disturbances and/or central pain in the opposite hemibody, analgesic or purely algesic thalamic syndrome characterised by contralateral anaesthesia (or hypaesthesia), contralateral weakness, ataxia and, often, persistent spontaneous pain. BASAL GANGLIA: Basal ganglia form a major centre in the complex extrapyramidal motor system, as opposed to the pyramidal motor system (corticobulbar and corticospinal pathways). Basal ganglia are involved in many neuronal pathways having emotional, motivational, associative and cognitive functions as well. The striatum (caudate nucleus, putamen and nucleus accumbens) receive inputs from all cortical areas and, throughout the thalamus, project principally to frontal lobe areas (prefrontal, premotor and supplementary motor areas) which are concerned with motor planning. These circuits: (i) have an important regulatory influence on cortex, providing information for both automatic and voluntary motor responses to the pyramidal system; (ii) play a role in predicting future events

  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. Cortico-Basal Ganglia Circuit Function in Psychiatric Disease.

    PubMed

    Gunaydin, Lisa A; Kreitzer, Anatol C

    2016-01-01

    Circuit dysfunction models of psychiatric disease posit that pathological behavior results from abnormal patterns of electrical activity in specific cells and circuits in the brain. Many psychiatric disorders are associated with abnormal activity in the prefrontal cortex and in the basal ganglia, a set of subcortical nuclei implicated in cognitive and motor control. Here we discuss the role of the basal ganglia and connected prefrontal regions in the etiology and treatment of obsessive-compulsive disorder, anxiety, and depression, emphasizing mechanistic work in rodent behavioral models to dissect causal cortico-basal ganglia circuits underlying discrete behavioral symptom domains relevant to these complex disorders. PMID:26667072

  7. 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. PMID:26956115

  8. Autoimmune basal ganglia disorders.

    PubMed

    Dale, Russell C; Brilot, Fabienne

    2012-11-01

    The basal ganglia are deep nuclei in the brain that include the caudate, putamen, globus pallidus, and substantia nigra. Pathological processes involving the basal ganglia often result in disorders of movement and behavior. A number of different autoimmune disorders predominantly involve the basal ganglia and can result in movement and psychiatric disorders. The classic basal ganglia autoimmune disorder is Sydenham chorea, a poststreptococcal neuropsychiatric disorder. Resurgence in the interest in Sydenham chorea is the result of the descriptions of other poststreptococcal neuropsychiatric disorders including tics and obsessive-compulsive disorder, broadly termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Encephalitic processes affecting the basal ganglia are also described including the syndromes basal ganglia encephalitis, encephalitis lethargica, and bilateral striatal necrosis. Last, systemic autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome can result in chorea or parkinsonism. Using paradigms learned from other autoantibody associated disorders, the authors discuss the autoantibody hypothesis and the role of systemic inflammation in autoimmune basal ganglia disorders. Identification of these entities is important as the clinician has an increasing therapeutic repertoire to modulate or suppress the aberrant immune system. PMID:22832771

  9. 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. PMID:23000204

  10. Cytokine Effects on the Basal Ganglia and Dopamine Function: the Subcortical Source of Inflammatory Malaise

    PubMed Central

    Felger, Jennifer C.; Miller, Andrew H.

    2012-01-01

    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. PMID:23000204

  11. Localization and Function of GABA Transporters GAT-1 and GAT-3 in the Basal Ganglia

    PubMed Central

    Jin, Xiao-Tao; Galvan, Adriana; Wichmann, Thomas; Smith, Yoland

    2011-01-01

    GABA transporter type 1 and 3 (GAT-1 and GAT-3, respectively) are the two main subtypes of GATs responsible for the regulation of extracellular GABA levels in the central nervous system. These transporters are widely expressed in neuronal (mainly GAT-1) and glial (mainly GAT-3) elements throughout the brain, but most data obtained so far relate to their role in the regulation of GABAA receptor-mediated postsynaptic tonic and phasic inhibition in the hippocampus, cerebral cortex and cerebellum. Taking into consideration the key role of GABAergic transmission within basal ganglia networks, and the importance for these systems to be properly balanced to mediate normal basal ganglia function, we analyzed in detail the localization and function of GAT-1 and GAT-3 in the globus pallidus of normal and Parkinsonian animals, in order to further understand the substrate and possible mechanisms by which GABA transporters may regulate basal ganglia outflow, and may become relevant targets for new therapeutic approaches for the treatment of basal ganglia-related disorders. In this review, we describe the general features of GATs in the basal ganglia, and give a detailed account of recent evidence that GAT-1 and GAT-3 regulation can have a major impact on the firing rate and pattern of basal ganglia neurons through pre- and post-synaptic GABAA- and GABAB-receptor-mediated effects. PMID:21847373

  12. Basal ganglia cholinergic and dopaminergic function in progressive supranuclear palsy.

    PubMed

    Warren, Naomi M; Piggott, Margaret A; Greally, Elizabeth; Lake, Michelle; Lees, Andrew J; Burn, David J

    2007-08-15

    Progressive Supranuclear Palsy (PSP) is a progressive neurodegenerative disorder. In contrast to Parkinson's disease (PD) and dementia with Lewy bodies (DLB), replacement therapy with dopaminergic and cholinergic agents in PSP has been disappointing. The neurochemical basis for this is unclear. Our objective was to measure dopaminergic and cholinergic receptors in the basal ganglia of PSP and control brains. We measured, autoradiographically, dopaminergic (dopamine transporter, 125I PE2I and dopamine D2 receptors, 125I epidepride) and cholinergic (nicotinic alpha4beta2 receptors, 125I 5IA85380 and muscarinic M1 receptors, 3H pirenzepine) parameters in the striatum and pallidum of pathologically confirmed PSP cases (n=15) and controls (n=32). In PSP, there was a marked loss of dopamine transporter and nicotinic alpha4beta2 binding in the striatum and pallidum, consistent with loss of nigrostriatal neurones. Striatal D2 receptors were increased in the caudate and muscarinic M1 receptors were unchanged compared with controls. These results do not account for the poor response to dopaminergic and cholinergic replacement therapies in PSP, and suggest relative preservation of postsynaptic striatal projection neurones bearing D2/M1 receptors. PMID:17534953

  13. [New findings on the morphology and motor function of basal ganglia].

    PubMed

    Marković, L; Berić, A; Marinković, R

    1996-01-01

    This paper presents results of new investigations on morphology and motor function of basal ganglia, which point to the fact that their dimensions are individual and not correlated with the dimension of the corresponding hemisphere. Basal ganglia motor function is studied on the basis of disturbances which occur if they are damaged, both in sick people and experimental animals. Analysis of recorded single-neuron activity, in animals and in patients undergoing special surgical procedures, is especially instructive for understanding this function. According to new insights there are at least five multiple neuronal regions: motor, oculomotor, limbic, dorsolateral prefrontal and lateral orbitofrontal region. Morphologic and functional studies partly disagree in interpreting connections among these regions. On the basis of functional studies it is considered that parallelism and functional separation exist, while on the basis of morphologic studies it is considered that at the level of basal ganglia output convergence occurs. New insights speak about parallelism and convergence at the same time. It is thought that inside basal ganglia motor region there are two divided systems, direct and indirect, which direct the output impulses towards talamus. The direct leads to facilitation of cortically started movements, and the indirect to suppression of unwanted motor behavior. On the basis of literature data we can conclude that basal ganglia support cortically generated movements, participate in sequential movements, suppress unwanted motor activity and in altered circumstances stop the course of started motor sequences allowing new, adequate motor activity. PMID:8926943

  14. 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

  15. The basal ganglia communicate with the cerebellum.

    PubMed

    Bostan, Andreea C; Dum, Richard P; Strick, Peter L

    2010-05-01

    The basal ganglia and cerebellum are major subcortical structures that influence not only movement, but putatively also cognition and affect. Both structures receive input from and send output to the cerebral cortex. Thus, the basal ganglia and cerebellum form multisynaptic loops with the cerebral cortex. Basal ganglia and cerebellar loops have been assumed to be anatomically separate and to perform distinct functional operations. We investigated whether there is any direct route for basal ganglia output to influence cerebellar function that is independent of the cerebral cortex. We injected rabies virus (RV) into selected regions of the cerebellar cortex in cebus monkeys and used retrograde transneuronal transport of the virus to determine the origin of multisynaptic inputs to the injection sites. We found that the subthalamic nucleus of the basal ganglia has a substantial disynaptic projection to the cerebellar cortex. This pathway provides a means for both normal and abnormal signals from the basal ganglia to influence cerebellar function. We previously showed that the dentate nucleus of the cerebellum has a disynaptic projection to an input stage of basal ganglia processing, the striatum. Taken together these results provide the anatomical substrate for substantial two-way communication between the basal ganglia and cerebellum. Thus, the two subcortical structures may be linked together to form an integrated functional network. PMID:20404184

  16. Striatal Cholinergic Interneurons Control Motor Behavior and Basal Ganglia Function in Experimental Parkinsonism.

    PubMed

    Maurice, Nicolas; Liberge, Martine; Jaouen, Florence; Ztaou, Samira; Hanini, Marwa; Camon, Jeremy; Deisseroth, Karl; Amalric, Marianne; Kerkerian-Le Goff, Lydia; Beurrier, Corinne

    2015-10-27

    Despite evidence showing that anticholinergic drugs are of clinical relevance in Parkinson's disease (PD), the causal role of striatal cholinergic interneurons (CINs) in PD pathophysiology remains elusive. Here, we show that optogenetic inhibition of CINs alleviates motor deficits in PD mouse models, providing direct demonstration for their implication in parkinsonian motor dysfunctions. As neural correlates, CIN inhibition in parkinsonian mice differentially impacts the excitability of striatal D1 and D2 medium spiny neurons, normalizes pathological bursting activity in the main basal ganglia output structure, and increases the functional weight of the direct striatonigral pathway in cortical information processing. By contrast, CIN inhibition in non-lesioned mice does not affect locomotor activity, equally modulates medium spiny neuron excitability, and does not modify spontaneous or cortically driven activity in the basal ganglia output, suggesting that the role of these interneurons in motor function is highly dependent on dopamine tone. PMID:26489458

  17. 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.

  18. [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. PMID:23568985

  19. Migraine attacks the Basal Ganglia

    PubMed Central

    2011-01-01

    Background With time, episodes of migraine headache afflict patients with increased frequency, longer duration and more intense pain. While episodic migraine may be defined as 1-14 attacks per month, there are no clear-cut phases defined, and those patients with low frequency may progress to high frequency episodic migraine and the latter may progress into chronic daily headache (> 15 attacks per month). The pathophysiology of this progression is completely unknown. Attempting to unravel this phenomenon, we used high field (human) brain imaging to compare functional responses, functional connectivity and brain morphology in patients whose migraine episodes did not progress (LF) to a matched (gender, age, age of onset and type of medication) group of patients whose migraine episodes progressed (HF). Results In comparison to LF patients, responses to pain in HF patients were significantly lower in the caudate, putamen and pallidum. Paradoxically, associated with these lower responses in HF patients, gray matter volume of the right and left caudate nuclei were significantly larger than in the LF patients. Functional connectivity analysis revealed additional differences between the two groups in regard to response to pain. Conclusions Supported by current understanding of basal ganglia role in pain processing, the findings suggest a significant role of the basal ganglia in the pathophysiology of the episodic migraine. PMID:21936901

  20. Task-set switching deficits in early-stage Huntington's disease: implications for basal ganglia function.

    PubMed

    Aron, Adam R; Watkins, Laura; Sahakian, Barbara J; Monsell, Stephen; Barker, Roger A; Robbins, Trevor W

    2003-07-01

    Executive functions are likely mediated by interconnected circuits including frontal lobe and basal ganglia structures. We assessed the executive function of task switching in patients with early-stage Huntington's disease (HD), a neurodegenerative disease affecting the basal ganglia. In two experiments, the HD patients had greater difficulty when switching than when repeating a task than matched controls, and this was true even when scaling for the overall slowing of the patients. In the first experiment, HD patients had a switching deficit even in a "pure" condition where they had to switch, predictably, and with substantial preparation time, between stimuli having only one possible response, indicating a switching deficit different from that for patients with Parkinson's disease or frontal lobe trauma, and possibly relating to inadequate activation of stimulus-response links or "response set." In the more elaborate second experiment, we could not account for the switching deficit of the patients in terms of inadequate preparation in advance of a switch, deficient suppression of task-set processing from the preswitch trial, or impaired suppression of interference due to the presence of a competing task set. Instead, we found that part of the switching deficit was due to elevated reaction time and errors on switch trials for a repeated response (same button press as on preswitch trial) relative to an alternated response (different button press from preswitch trial). We argue that this elevated "repetition effect" for the HD patients is due to excessive inhibition of the just-performed response in advance of a switch. Alterations in the "response-setting" process alone (Experiment 1) and both the response-setting and "response inhibition" process (Experiment 2) probably arise from striatal pathology in HD, thus accounting for the task-switching deficits and showing how basal ganglia implemented response processes may underpin executive function. PMID:12965037

  1. fMRI of cocaine self-administration in macaques reveals functional inhibition of basal ganglia.

    PubMed

    Mandeville, Joseph B; Choi, Ji-Kyung; Jarraya, Bechir; Rosen, Bruce R; Jenkins, Bruce G; Vanduffel, Wim

    2011-05-01

    Disparities in cocaine-induced neurochemical and metabolic responses between human beings and rodents motivate the use of non-human primates (NHP) to model consequences of repeated cocaine exposure in human subjects. To characterize the functional response to cocaine infusion in NHP brain, we employed contrast-enhanced fMRI during both non-contingent injection of drug and self-administration of cocaine in the magnet. Cocaine robustly decreased cerebral blood volume (CBV) throughout basal ganglia and motor/pre-motor cortex and produced subtle functional inhibition of prefrontal cortex. No brain regions exhibited significant elevation of CBV in response to cocaine challenge. Theses effects in NHP brain are opposite in sign to the cocaine-induced fMRI response in rats, but consistent with previous measurements in NHP based on glucose metabolism. Because the striatal ratio of D2 to D1 receptors is larger in human beings and NHP than rats, we hypothesize that the inhibitory effects of D2 receptor binding dominate the functional response in primates, whereas excitatory D1 receptor stimulation predominates in the rat. If the NHP accurately models the human response to cocaine, downregulation of D2 receptors in human cocaine-abusing populations can be expected to blunt cocaine-induced functional responses, contributing to the weak and variable fMRI responses reported in human basal ganglia following cocaine infusion. PMID:21307843

  2. Redefining functional models of basal ganglia organization: role for the posteroventral pallidum in linguistic processing?

    PubMed

    Whelan, Brooke-Mai; Murdoch, Bruce E; Theodoros, Deborah G; Darnell, Ross; Silburn, Peter; Hall, Bruce

    2004-11-01

    Traditionally the basal ganglia have been implicated in motor behavior, as they are involved in both the execution of automatic actions and the modification of ongoing actions in novel contexts. Corresponding to cognition, the role of the basal ganglia has not been defined as explicitly. Relative to linguistic processes, contemporary theories of subcortical participation in language have endorsed a role for the globus pallidus internus (GPi) in the control of lexical-semantic operations. However, attempts to empirically validate these postulates have been largely limited to neuropsychological investigations of verbal fluency abilities subsequent to pallidotomy. We evaluated the impact of bilateral posteroventral pallidotomy (BPVP) on language function across a range of general and high-level linguistic abilities, and validated/extended working theories of pallidal participation in language. Comprehensive linguistic profiles were compiled up to 1 month before and 3 months after BPVP in 6 subjects with Parkinson's disease (PD). Commensurate linguistic profiles were also gathered over a 3-month period for a nonsurgical control cohort of 16 subjects with PD and a group of 16 non-neurologically impaired controls (NC). Nonparametric between-groups comparisons were conducted and reliable change indices calculated, relative to baseline/3-month follow-up difference scores. Group-wise statistical comparisons between the three groups failed to reveal significant postoperative changes in language performance. Case-by-case data analysis relative to clinically consequential change indices revealed reliable alterations in performance across several language variables as a consequence of BPVP. These findings lend support to models of subcortical participation in language, which promote a role for the GPi in lexical-semantic manipulation mechanisms. Concomitant improvements and decrements in postoperative performance were interpreted within the context of additive and subtractive

  3. Longitudinal Assessment of Motor Recovery of Contralateral Hand after Basal Ganglia Infarction Using Functional Magnetic Resonance Imaging

    PubMed Central

    Fu, Yue; Zhang, Quan; Yu, Chunshui; Zhang, Jing; Wang, Ning; Zuo, Shanhuai; Zhang, Ningnannan

    2016-01-01

    We used functional fMRI to study the brain activation during active finger movements at different time points during the recovery phase following basal ganglia infarction. Four hemiplegic patients with basal ganglia infarction were serially evaluated at different time points spanning the acute and chronic phase using fMRI. To evaluate motor recovery, the patients were asked to perform functional tasks arranged in a block design manner with their hand. On follow-up (chronic phase), three patients achieved significant recovery of motor function of affected limbs. Activation of bilateral sensorimotor cortex (SMC) was observed in two of these patients, while activation of cerebellum was observed in all patients. No remarkable recovery of motor function was noted in one patient with left basal ganglia infarction. In this patient, the activation domain was located in SMC of both sides in acute phase and in ipsilateral SMC in chronic phase. Contralateral SMC appears to be involved in the functional rehabilitation following basal ganglia infarction. The cerebellum may act as an intermediary during functional recovery following basal ganglia infarction. The activation domain associated with active finger movement may be bilateral in acute phase; one patient was ipsilateral in the chronic stage. PMID:27069924

  4. Longitudinal Assessment of Motor Recovery of Contralateral Hand after Basal Ganglia Infarction Using Functional Magnetic Resonance Imaging.

    PubMed

    Fu, Yue; Zhang, Quan; Yu, Chunshui; Zhang, Jing; Wang, Ning; Zuo, Shanhuai; Zhang, Ningnannan

    2016-01-01

    We used functional fMRI to study the brain activation during active finger movements at different time points during the recovery phase following basal ganglia infarction. Four hemiplegic patients with basal ganglia infarction were serially evaluated at different time points spanning the acute and chronic phase using fMRI. To evaluate motor recovery, the patients were asked to perform functional tasks arranged in a block design manner with their hand. On follow-up (chronic phase), three patients achieved significant recovery of motor function of affected limbs. Activation of bilateral sensorimotor cortex (SMC) was observed in two of these patients, while activation of cerebellum was observed in all patients. No remarkable recovery of motor function was noted in one patient with left basal ganglia infarction. In this patient, the activation domain was located in SMC of both sides in acute phase and in ipsilateral SMC in chronic phase. Contralateral SMC appears to be involved in the functional rehabilitation following basal ganglia infarction. The cerebellum may act as an intermediary during functional recovery following basal ganglia infarction. The activation domain associated with active finger movement may be bilateral in acute phase; one patient was ipsilateral in the chronic stage. PMID:27069924

  5. Extrastriatal Dopaminergic Circuits of the Basal Ganglia

    PubMed Central

    Rommelfanger, Karen S.; Wichmann, Thomas

    2010-01-01

    The basal ganglia are comprised of the striatum, the external and internal segment of the globus pallidus (GPe and GPi, respectively), the subthalamic nucleus (STN), and the substantia nigra pars compacta and reticulata (SNc and SNr, respectively). Dopamine has long been identified as an important modulator of basal ganglia function in the striatum, and disturbances of striatal dopaminergic transmission have been implicated in diseases such as Parkinson's disease (PD), addiction and attention deficit hyperactivity disorder. However, recent evidence suggests that dopamine may also modulate basal ganglia function at sites outside of the striatum, and that changes in dopaminergic transmission at these sites may contribute to the symptoms of PD and other neuropsychiatric disorders. This review summarizes the current knowledge of the anatomy, functional effects and behavioral consequences of the dopaminergic innervation to the GPe, GPi, STN, and SNr. Further insights into the dopaminergic modulation of basal ganglia function at extrastriatal sites may provide us with opportunities to develop new and more specific strategies for treating disorders of basal ganglia dysfunction. PMID:21103009

  6. The role of exercise in facilitating basal ganglia function in Parkinson’s disease

    PubMed Central

    Petzinger, Giselle M; Fisher, Beth E; Akopian, Garnik; Holschneider, Daniel P; Wood, Ruth; Walsh, John P; Lund, Brett; Meshul, Charles; Vuckovic, Marta; Jakowec, Michael W

    2012-01-01

    SUMMARY Epidemiological and clinical studies have suggested that exercise is beneficial for patients with Parkinson’s disease (PD). Through research in normal (noninjured) animals, neuroscientists have begun to understand the mechanisms in the brain by which behavioral training and exercise facilitates improvement in motor behavior through modulation of neuronal function and structure, called experience-dependent neuroplasticity. Recent studies are beginning to reveal molecules and downstream signaling pathways that are regulated during exercise and motor learning in animal models of PD and that are important in driving protective and/or adaptive changes in neuronal connections of the basal ganglia and related circuitry. These molecules include the neurotransmitters dopamine and glutamate (and their respective receptors) as well as neurotrophic factors (brain-derived neurotrophic factor). In parallel, human exercise studies have been important in revealing ‘proof of concept’ including examining the types and parameters of exercise that are important for behavioral/functional improvements and brain changes; the feasibility of incorporating and maintaining an exercise program in individuals with motor disability; and, importantly, the translation and investigation of exercise effects observed in animal studies to exercise effects on brain and behavior in individuals with PD. In this article we highlight findings from both animal and human exercise studies that provide insight into brain changes of the basal ganglia and its related circuitry and that support potentially key parameters of exercise that may lead to long-term benefit and disease modification in PD. In addition, we discuss the current and future impact on patient care and point out gaps in our knowledge where continuing research is needed. Elucidation of exercise parameters important in driving neuroplasticity, as well as the accompanying mechanisms that underlie experience-dependent neuroplasticity

  7. 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

  8. 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

  9. Functional Correlates of Exaggerated Oscillatory Activity in Basal Ganglia Output in Hemiparkinsonian Rats

    PubMed Central

    Brazhnik, Elena; Novikov, Nikolay; McCoy, Alex J.; Cruz, Ana V.; Walters, Judith R.

    2014-01-01

    Exaggerated beta range (13–30 Hz) synchronized activity is observed in the basal ganglia of Parkinson’s disease (PD) patients during implantation of deep brain stimulation electrodes and is thought to contribute to the motor symptoms of this disorder. To explore the translational potential of similar activity observed in a rat model of PD, local field potentials (LFP) and spiking activity in basal ganglia output were characterized in rats with unilateral dopamine cell lesion during a range of behaviors. A circular treadmill was used to assess activity during walking; hemiparkinsonian rats could maintain a steady gait when oriented ipsiversive to the lesioned hemisphere, but were less effective at walking when oriented contraversive to lesion. Dramatic increases in substantia nigra pars reticulata (SNpr) LFP oscillatory activity and spike-LFP synchronization were observed within the beta/low gamma range (12–40 Hz) in the lesioned hemisphere, relative to the non-lesioned hemisphere, with the dominant frequency of spike-LFP entrainment and LFP power varying with behavioral state. At 3 weeks post-lesion, the mean dominant entrainment frequency during ipsiversive treadmill walking and grooming was 34 Hz. Other behaviors were associated with lower mean entrainment frequencies: 27–28 Hz during alert non-walking and REM, 17 Hz during rest and 21 Hz during urethane anesthesia with sensory stimulation. SNpr spike-LFP entrainment frequency was stable during individual treadmill walking epochs, but increased gradually over weeks post-lesion. In contrast, SNpr LFP power in the 25–40 Hz range was greatest at the initiation of each walking epoch, and decreased during walking to stabilize by 6 min at 49% of initial values. Power was further modulated in conjunction with the 1.5 s stepping rhythm. Administration of L-dopa improved contraversive treadmill walking in correlation with a reduction in SNpr 25–40 Hz LFP power and spike synchronization in the dopamine cell

  10. Recovery of language function in Korean-Japanese crossed bilingual aphasia following right basal ganglia hemorrhage.

    PubMed

    Lee, Boram; Moon, Hyun Im; Lim, Sung Hee; Cho, Hyesuk; Choi, Hyunjoo; Pyun, Sung-Bom

    2016-06-01

    Few studies have investigated language recovery patterns and the mechanisms of crossed bilingual aphasia following a subcortical stroke. In particular, Korean-Japanese crossed bilingual aphasia has not been reported. A 47-year-old, right-handed man was diagnosed with an extensive right basal ganglia hemorrhage. He was bilingual, fluent in both Korean and Japanese. After his stroke, the patient presented with crossed aphasia. We investigated changes in the Korean (L1) and Japanese (L2) language recovery patterns. Both Korean and Japanese versions of the Western Aphasia Battery (WAB) were completed one month after the stroke, and functional magnetic resonance imaging (fMRI) was performed using picture-naming tasks. The WAB showed a paradoxical pattern of bilingual aphasia, with an aphasia quotient (AQ) of 32 for Korean and 50.6 for Japanese, with Broca's aphasia. The patient scored better in the Japanese version of all domains of the tests. The fMRI study showed left lateralized activation in both language tasks, especially in the inferior frontal gyrus. After six months of language therapy targeting L1, the Korean-WAB score improved significantly, while the Japanese-WAB score showed slight improvement. In this case, the subcortical lesion contributed to crossed bilingual aphasia more highly affecting L1 due to loss of the cortico-subcortical control mechanism in the dominant hemisphere. The paradoxical pattern of bilingual aphasia disappeared after lengthy language therapy targeting L1, and the therapy effect did not transfer to L2. Language recovery in L1 might have been accomplished by reintegrating language networks, including the contralesional language homologue area in the left hemisphere. PMID:26853846

  11. What do the basal ganglia do?

    PubMed

    Brown, P; Marsden, C D

    1998-06-13

    We propose that the basal ganglia support a basic attentional mechanism operating to bind input to output in the executive forebrain. Such focused attention provides the automatic link between voluntary effort, sensory input, and the calling up and operation of a sequence of motor programmes or thoughts. The physiological basis for this attentional mechanism may lie in the tendency of distributed, but related, cortical activities to synchronise in the gamma (30 to 50 Hz) band, as occurs in the visual cortex. Coherent and synchronised elements are more effective when convergence occurs during successive stages of processing, and in this way may come together to give the one gestalt or action. We suggest that the basal ganglia have a major role in facilitating this aspect of neuronal processing in the forebrain, and that loss of this function contributes to parkinsonism and abulia. PMID:9635969

  12. 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. PMID:25514518

  13. Functional lateralization in cingulate cortex predicts motor recovery after basal ganglia stroke.

    PubMed

    Li, Yao; Chen, Zengai; Su, Xin; Zhang, Xiaoliu; Wang, Ping; Zhu, Yajing; Xu, Qun; Xu, Jianrong; Tong, Shanbao

    2016-02-01

    The basal ganglia (BG) is involved in higher order motor control such as movement planning and execution of complex motor synergies. Neuroimaging study on stroke patients specifically with BG lesions would help to clarify the consequence of BG damage on motor control. In this paper, we performed a longitudinal study in the stroke patients with lesions in BG regions across three motor recovery stages, i.e., less than 2week (Session 1), 1-3m (Session 2) and more than 3m (Session 3). The patients showed an activation shift from bilateral hemispheres during early sessions (<3m) to the ipsilesional cortex in late session (>3m), suggesting a compensation effect from the contralesional hemisphere during motor recovery. We found that the lateralization of cerebellum(CB) for affected hand task correlated with patients' concurrent Fugl-Meyer index (FMI) in Session 2. Moreover, the cingulate cortex lateralization index in Session 2 was shown to significantly correlate with subsequent FMI change between Session 3 and Session 2, which serves as a prognostic marker for motor recovery. Our findings consolidated the close interactions between BG and CB during the motor recovery after stroke. The dominance of activation in contralateral cingulate cortex was associated with a better motor recovery, suggesting the important role of ipsilesional attention modulation in the early stage after BG stroke. PMID:26742641

  14. 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

  15. Functional Relevance of Different Basal Ganglia Pathways Investigated in a Spiking Model with Reward Dependent Plasticity

    PubMed Central

    Berthet, Pierre; Lindahl, Mikael; Tully, Philip J.; Hellgren-Kotaleski, Jeanette; Lansner, Anders

    2016-01-01

    The brain enables animals to behaviorally adapt in order to survive in a complex and dynamic environment, but how reward-oriented behaviors are achieved and computed by its underlying neural circuitry is an open question. To address this concern, we have developed a spiking model of the basal ganglia (BG) that learns to dis-inhibit the action leading to a reward despite ongoing changes in the reward schedule. The architecture of the network features the two pathways commonly described in BG, the direct (denoted D1) and the indirect (denoted D2) pathway, as well as a loop involving striatum and the dopaminergic system. The activity of these dopaminergic neurons conveys the reward prediction error (RPE), which determines the magnitude of synaptic plasticity within the different pathways. All plastic connections implement a versatile four-factor learning rule derived from Bayesian inference that depends upon pre- and post-synaptic activity, receptor type, and dopamine level. Synaptic weight updates occur in the D1 or D2 pathways depending on the sign of the RPE, and an efference copy informs upstream nuclei about the action selected. We demonstrate successful performance of the system in a multiple-choice learning task with a transiently changing reward schedule. We simulate lesioning of the various pathways and show that a condition without the D2 pathway fares worse than one without D1. Additionally, we simulate the degeneration observed in Parkinson's disease (PD) by decreasing the number of dopaminergic neurons during learning. The results suggest that the D1 pathway impairment in PD might have been overlooked. Furthermore, an analysis of the alterations in the synaptic weights shows that using the absolute reward value instead of the RPE leads to a larger change in D1. PMID:27493625

  16. 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

  17. Functional Relevance of Different Basal Ganglia Pathways Investigated in a Spiking Model with Reward Dependent Plasticity.

    PubMed

    Berthet, Pierre; Lindahl, Mikael; Tully, Philip J; Hellgren-Kotaleski, Jeanette; Lansner, Anders

    2016-01-01

    The brain enables animals to behaviorally adapt in order to survive in a complex and dynamic environment, but how reward-oriented behaviors are achieved and computed by its underlying neural circuitry is an open question. To address this concern, we have developed a spiking model of the basal ganglia (BG) that learns to dis-inhibit the action leading to a reward despite ongoing changes in the reward schedule. The architecture of the network features the two pathways commonly described in BG, the direct (denoted D1) and the indirect (denoted D2) pathway, as well as a loop involving striatum and the dopaminergic system. The activity of these dopaminergic neurons conveys the reward prediction error (RPE), which determines the magnitude of synaptic plasticity within the different pathways. All plastic connections implement a versatile four-factor learning rule derived from Bayesian inference that depends upon pre- and post-synaptic activity, receptor type, and dopamine level. Synaptic weight updates occur in the D1 or D2 pathways depending on the sign of the RPE, and an efference copy informs upstream nuclei about the action selected. We demonstrate successful performance of the system in a multiple-choice learning task with a transiently changing reward schedule. We simulate lesioning of the various pathways and show that a condition without the D2 pathway fares worse than one without D1. Additionally, we simulate the degeneration observed in Parkinson's disease (PD) by decreasing the number of dopaminergic neurons during learning. The results suggest that the D1 pathway impairment in PD might have been overlooked. Furthermore, an analysis of the alterations in the synaptic weights shows that using the absolute reward value instead of the RPE leads to a larger change in D1. PMID:27493625

  18. 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

  19. Pedunculopontine nucleus and basal ganglia: distant relatives or part of the same family?

    PubMed

    Mena-Segovia, Juan; Bolam, J Paul; Magill, Peter J

    2004-10-01

    The basal ganglia are more highly interconnected with the pedunculopontine tegmental nucleus (PPN) than with any other brain region. Regulation and relay of basal ganglia activity are two key functions of the PPN. The PPN provides an interface for the basal ganglia to influence sleep and waking, and the two structures are similarly implicated in learning, reward and other cognitive functions. Perturbations of basal ganglia activity have consequences for the PPN and vice versa, exemplified by their interdependencies in motor function and Parkinson's disease. Thus, close anatomical and physiological links between the PPN and basal ganglia make it increasingly difficult to consider the two as separate functional entities. PMID:15374668

  20. Freezing of gait in Parkinson's disease is associated with functional decoupling between the cognitive control network and the basal ganglia.

    PubMed

    Shine, James M; Matar, Elie; Ward, Philip B; Frank, Michael J; Moustafa, Ahmed A; Pearson, Mark; Naismith, Sharon L; Lewis, Simon J G

    2013-12-01

    Recent neuroimaging evidence has led to the proposal that freezing of gait in Parkinson's disease is due to dysfunctional interactions between frontoparietal cortical regions and subcortical structures, such as the striatum. However, to date, no study has employed task-based functional connectivity analyses to explore this hypothesis. In this study, we used a data-driven multivariate approach to explore the impaired communication between distributed neuronal networks in 10 patients with Parkinson's disease and freezing of gait, and 10 matched patients with no clinical history of freezing behaviour. Patients performed a virtual reality gait task on two separate occasions (once ON and once OFF their regular dopaminergic medication) while functional magnetic resonance imaging data were collected. Group-level independent component analysis was used to extract the subject-specific time courses associated with five well-known neuronal networks: the motor network, the right- and left cognitive control networks, the ventral attention network and the basal ganglia network. We subsequently analysed both the activation and connectivity of these neuronal networks between the two groups with respect to dopaminergic state and cognitive load while performing the virtual reality gait task. During task performance, all patients used the left cognitive control network and the ventral attention network and in addition, showed increased connectivity between the bilateral cognitive control networks. However, patients with freezing demonstrated functional decoupling between the basal ganglia network and the cognitive control network in each hemisphere. This decoupling was also associated with paroxysmal motor arrests. These results support the hypothesis that freezing behaviour in Parkinson's disease is because of impaired communication between complimentary yet competing neural networks. PMID:24142148

  1. Shaping Action Sequences in Basal Ganglia Circuits

    PubMed Central

    Jin, Xin; Costa, Rui M

    2015-01-01

    Many behaviors necessary for organism survival are learned anew and become organized as complex sequences of actions. Recent studies suggest that cortico-basal ganglia circuits are important for chunking isolated movements into precise and robust action sequences that permit the achievement of particular goals. During sequence learning many neurons in the basal ganglia develop sequence-related activity - related to the initiation, execution, and termination of sequences - suggesting that action sequences are processed as action units. Corticostriatal plasticity is critical for the crystallization of action sequences, and for the development of sequence-related neural activity. Furthermore, this sequence-related activity is differentially expressed in direct and indirect basal ganglia pathways. These findings have implications for understanding the symptoms associated with movement and psychiatric disorders. PMID:26189204

  2. Dopamine agonists can improve pure apathy associated with lesions of the prefrontal-basal ganglia functional system.

    PubMed

    Blundo, Carlo; Gerace, Carmela

    2015-07-01

    Apathy is a common neurobehavioral symptom of other syndromes or a syndrome per se which occurs in a variety of neuropsychiatric disorders. Apathy depends on disruption of emotional, cognitive, and behavioral functions. Six brain-damaged patients were assessed, including five patients with unilateral or bilateral focal lesions of the basal ganglia or the thalamus (showing apathy due to an auto-activation deficit) and one patient with bilateral lesions in the limbic temporomesial cortex associated with a form of emotional-affective apathy. A significant and persistent improvement of apathy was observed in all patients after treatment with dopamine agonists such as pramipexole, ropinirole, and rotigotine. These results confirm preliminary reports on the beneficial effects of dopamine agonist agents on apathy and suggest that this syndrome can be treatable in many cases. PMID:25876742

  3. 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. PMID:27144466

  4. Basal ganglia germinoma with progressive cerebral hemiatrophy.

    PubMed

    Liu, E; Robertson, R L; du Plessis, A; Pomeroy, S L

    1999-04-01

    The authors describe a 7-year-old Chinese-American female with a germinoma of the basal ganglia who presented with progressive hemiparesis and cerebral hemiatrophy. The additional finding of markedly elevated antiphospholipid antibodies suggests the possibility of an autoimmune pathogenesis for the progressive cerebral atrophy, as well as the later development of cognitive decline, tics, and obsessive-compulsive behaviors. PMID:10328283

  5. Basal Ganglia Germinoma in an Adult.

    PubMed

    Vialatte de Pémille, Clément; Bielle, Franck; Mokhtari, Karima; Kerboua, Esma; Alapetite, Claire; Idbaih, Ahmed

    2016-08-01

    Intracranial germinoma is a rare primary brain cancer, usually located within the midline and mainly affecting Asian pediatric patients. Interestingly, we report here the peculiar case of a young North-African adult patient suffering from a basal ganglia germinoma without the classical ipsilateral cerebral hemiatrophy associated with this location. PMID:27241091

  6. Dopamine-glutamate interactions in the basal ganglia.

    PubMed

    Schmidt, W J

    1998-01-01

    In an attempt to formulate a working hypothesis of basal-ganglia functions, arguments are considered suggesting that the basal ganglia are involved in a process of response selection i.e. in the facilitation of "wanted" and in the suppression of "unwanted" behaviour. The meso-accumbal dopamine-system is considered to mediate natural and drug-induced reward and sensitization. The meso-striatal dopamine-system seems to fulfill similar functions: It may mediate reinforcement which strengthens a given behaviour when elicited subsequently, but which is not experienced as reward or hedonia. Glutamate as the transmitter of the corticofugal projections to the basal ganglia nuclei and of the subthalamic neurons is critically involved in basal ganglia functions and dysfunctions; for example Parkinson's disease can be considered to be a secondary hyperglutamatergic disease. Additionally, glutamate is an essential factor in the plasticity response of the basal-ganglia. However, opposite to previous suggestions, the NMDA-receptor blocker MK-801 does not prevent psychostimulant- nor morphine-induced day to day increase (sensitization) of locomotion. Also the day to day increase of haloperidol-induced catalepsy was not prevented by MK-801. PMID:9871434

  7. Exploring the cognitive and motor functions of the basal ganglia: an integrative review of computational cognitive neuroscience models

    PubMed Central

    Helie, Sebastien; Chakravarthy, Srinivasa; Moustafa, Ahmed A.

    2013-01-01

    Many computational models of the basal ganglia (BG) have been proposed over the past twenty-five years. While computational neuroscience models have focused on closely matching the neurobiology of the BG, computational cognitive neuroscience (CCN) models have focused on how the BG can be used to implement cognitive and motor functions. This review article focuses on CCN models of the BG and how they use the neuroanatomy of the BG to account for cognitive and motor functions such as categorization, instrumental conditioning, probabilistic learning, working memory, sequence learning, automaticity, reaching, handwriting, and eye saccades. A total of 19 BG models accounting for one or more of these functions are reviewed and compared. The review concludes with a discussion of the limitations of existing CCN models of the BG and prescriptions for future modeling, including the need for computational models of the BG that can simultaneously account for cognitive and motor functions, and the need for a more complete specification of the role of the BG in behavioral functions. PMID:24367325

  8. 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. PMID:25567372

  9. 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

  10. Oscillations and the basal ganglia: Motor control and beyond

    PubMed Central

    Brittain, John-Stuart; Brown, Peter

    2016-01-01

    Oscillations form a ubiquitous feature of the central nervous system. Evidence is accruing from cortical and sub-cortical recordings that these rhythms may be functionally important, although the precise details of their roles remain unclear. The basal ganglia share this predilection for rhythmic activity which, as we see in Parkinson’s disease, becomes further enhanced in the dopamine depleted state. While certain cortical rhythms appear to penetrate the basal ganglia, others are transformed or blocked. Here, we discuss the functional association of oscillations in the basal ganglia and their relationship with cortical activity. We further explore the neural underpinnings of such oscillatory activity, including the important balance to be struck between facilitating information transmission and limiting information coding capacity. Finally, we introduce the notion that synchronised oscillatory activity can be broadly categorised as immutability promoting rhythms that reinforce incumbent processes, and mutability promoting rhythms that favour novel processing. PMID:23711535

  11. Time representation in reinforcement learning models of the basal ganglia

    PubMed Central

    Gershman, Samuel J.; Moustafa, Ahmed A.; Ludvig, Elliot A.

    2014-01-01

    Reinforcement learning (RL) models have been influential in understanding many aspects of basal ganglia function, from reward prediction to action selection. Time plays an important role in these models, but there is still no theoretical consensus about what kind of time representation is used by the basal ganglia. We review several theoretical accounts and their supporting evidence. We then discuss the relationship between RL models and the timing mechanisms that have been attributed to the basal ganglia. We hypothesize that a single computational system may underlie both RL and interval timing—the perception of duration in the range of seconds to hours. This hypothesis, which extends earlier models by incorporating a time-sensitive action selection mechanism, may have important implications for understanding disorders like Parkinson's disease in which both decision making and timing are impaired. PMID:24409138

  12. BASAL GANGLIA PATHOLOGY IN SCHIZOPHRENIA: DOPAMINE CONNECTIONS and ANOMALIES

    PubMed Central

    Perez-Costas, Emma; Melendez-Ferro, Miguel; Roberts, Rosalinda C.

    2010-01-01

    Schizophrenia is a severe mental illness that affects 1% of the world population. The disease usually manifests itself in early adulthood with hallucinations, delusions, cognitive and emotional disturbances and disorganized thought and behavior. Dopamine was the first neurotransmitter to be implicated in the disease, and though no longer the only suspect in schizophrenia pathophysiology, it obviously plays an important role. The basal ganglia are the site of most of the dopamine neurons in the brain and the target of antipsychotic drugs. In this review we will start with an overview of basal ganglia anatomy emphasizing dopamine circuitry. Then, we will review the major deficits in dopamine function in schizophrenia, emphasizing the role of excessive dopamine in the basal ganglia and the link to psychosis. PMID:20089137

  13. [Parkinson's disease and cortico-Basal Ganglia circuits].

    PubMed

    Pan, Ming-Kai; Tai, Chun-Hwei; Kuo, Chung-Chin

    2010-09-01

    Cortico-basal ganglia circuit model has been studied extensively after it was first proposed by Alexander and Crutcher in 1990. This model accurately predicted the hyperactivity of indirect pathway and subthalamic nucleus(STN) in the dopamine deficiency state of Parkinson's disease (PD), prompting the experimental approaches of lesioning STN in parkinsonian primates. Application of these successful experiences with STN lesions in the reversal of parkinsonian symptoms to human PD patients facilitates the development of STN deep brain stimulation (DBS), which has become one of the most important therapies for PD in recent years. Although the classical model of the cortico-basal ganglia circuits by Alexander and Crutcher has provided many important insights into the basal ganglia function, the functional role of cortico-subthalamic "hyperdirect" pathway in the circuits has been relatively neglected. The first part of this article summarizes recent development concerning the cortico-basal ganglia circuits, especially emphasizing the importance of the hyperdirect pathway. In the second part of this article, we would describe the analyses of gross corticobasal ganglia circuit electrophysiological findings, especially emphasizing the coherence between two oscillating signals. We would also discuss the correlation between these parameters and the motor dysfunction, and its pathophysiological implications in PD. PMID:20824544

  14. Covert skill learning in a cortical-basal ganglia circuit.

    PubMed

    Charlesworth, Jonathan D; Warren, Timothy L; Brainard, Michael S

    2012-06-14

    We learn complex skills such as speech and dance through a gradual process of trial and error. Cortical-basal ganglia circuits have an important yet unresolved function in this trial-and-error skill learning; influential 'actor-critic' models propose that basal ganglia circuits generate a variety of behaviours during training and learn to implement the successful behaviours in their repertoire. Here we show that the anterior forebrain pathway (AFP), a cortical-basal ganglia circuit, contributes to skill learning even when it does not contribute to such 'exploratory' variation in behavioural performance during training. Blocking the output of the AFP while training Bengalese finches to modify their songs prevented the gradual improvement that normally occurs in this complex skill during training. However, unblocking the output of the AFP after training caused an immediate transition from naive performance to excellent performance, indicating that the AFP covertly gained the ability to implement learned skill performance without contributing to skill practice. In contrast, inactivating the output nucleus of the AFP during training completely prevented learning, indicating that learning requires activity within the AFP during training. Our results suggest a revised model of skill learning: basal ganglia circuits can monitor the consequences of behavioural variation produced by other brain regions and then direct those brain regions to implement more successful behaviours. The ability of the AFP to identify successful performances generated by other brain regions indicates that basal ganglia circuits receive a detailed efference copy of premotor activity in those regions. The capacity of the AFP to implement successful performances that were initially produced by other brain regions indicates precise functional connections between basal ganglia circuits and the motor regions that directly control performance. PMID:22699618

  15. Learning Reward Uncertainty in the Basal Ganglia.

    PubMed

    Mikhael, John G; Bogacz, Rafal

    2016-09-01

    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

  16. Active decorrelation in the basal ganglia.

    PubMed

    Wilson, C J

    2013-10-10

    The cytoarchitecturally-homogeneous appearance of the globus pallidus, subthalamic nucleus and substantia nigra has long been said to imply a high degree of afferent convergence and sharing of inputs by nearby neurons. Moreover, axon collaterals of neurons in the external segment of the globus pallidus and the substantia nigra pars reticulata arborize locally and make inhibitory synapses on other cells of the same type. These features suggest that the connectivity of the basal ganglia may impose spike-time correlations among the cells, and it has been puzzling that experimental studies have failed to demonstrate such correlations. One possible solution arises from studies of firing patterns in basal ganglia cells, which reveal that they are nearly all pacemaker cells. Their high rate of firing does not depend on synaptic excitation, but they fire irregularly because a dense barrage of synaptic inputs normally perturbs the timing of their autonomous activity. Theoretical and computational studies show that the responses of repetitively-firing neurons to shared input or mutual synaptic coupling often defy classical intuitions about temporal synaptic integration. The patterns of spike-timing among such neurons depend on the ionic mechanism of pacemaking, the level of background uncorrelated cellular and synaptic noise, and the firing rates of the neurons, as well as the properties of their synaptic connections. Application of these concepts to the basal ganglia circuitry suggests that the connectivity and physiology of these nuclei may be configured to prevent the establishment of permanent spike-timing relationships between neurons. The development of highly synchronous oscillatory patterns of activity in Parkinson's disease may result from the loss of pacemaking by some basal ganglia neurons, and accompanying breakdown of the mechanisms responsible for active decorrelation. PMID:23892007

  17. A key role of the basal ganglia in pain and analgesia - insights gained through human functional imaging

    PubMed Central

    2010-01-01

    The basal ganglia (BG) are composed of several nuclei involved in neural processing related to the execution of motor, cognitive and emotional activities. Preclinical and clinical data have implicated a role for these structures in pain processing. Recently neuroimaging has added important information on BG activation in conditions of acute pain, chronic pain and as a result of drug effects. Our current understanding of alterations in cortical and sub-cortical regions in pain suggests that the BG are uniquely involved in thalamo-cortico-BG loops to integrate many aspects of pain. These include the integration of motor, emotional, autonomic and cognitive responses to pain. PMID:20465845

  18. 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. PMID:27108246

  19. Mössbauer spectroscopy of Basal Ganglia

    SciTech Connect

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

    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.

  20. Is Broca's area part of a basal ganglia thalamocortical circuit?

    PubMed

    Ullman, Michael T

    2006-05-01

    The cortex constituting Broca's area does not exist in isolation. Rather, like other cortical regions, Broca's area is connected to other brain structures, which likely play closely related functional roles. This paper focuses on the basal ganglia, a set of subcortical structures that project through topographically organized "channels" via the thalamus to different frontal regions. It is hypothesized that the basal ganglia project to Broca's area. This circuitry is further posited to encompass at least two channels. One channel can be characterized as subserving procedural memory, while the other underlies the retrieval of knowledge from declarative memory. These hypotheses are supported by both anatomical and functional evidence. Implications and issues for further investigation are discussed. PMID:16881254

  1. Cerebellar networks with the cerebral cortex and basal ganglia.

    PubMed

    Bostan, Andreea C; Dum, Richard P; Strick, Peter L

    2013-05-01

    The dominant view of cerebellar function has been that it is exclusively concerned with motor control and coordination. Recent findings from neuroanatomical, behavioral, and imaging studies have profoundly changed this view. Neuroanatomical studies using virus transneuronal tracers have demonstrated that cerebellar output reaches vast areas of the neocortex, including regions of prefrontal and posterior parietal cortex. Furthermore, it has recently become clear that the cerebellum is reciprocally connected with the basal ganglia, which suggests that the two subcortical structures are part of a densely interconnected network. Taken together, these findings elucidate the neuroanatomical substrate for cerebellar involvement in non-motor functions mediated by the prefrontal and posterior parietal cortex, as well as in processes traditionally associated with the basal ganglia. PMID:23579055

  2. Mineralizing angiopathy with basal ganglia stroke in an infant

    PubMed Central

    Jain, Puneet; Kishore, Praveen; Bhasin, Jasjit Singh; Arya, Subhash Chand

    2015-01-01

    Basal ganglia stroke is known following trivial head trauma. Recently a distinct clinic-radiological entity termed ‘mineralizing angiopathy’ was described. We report an infant who developed basal ganglia stroke following trivial fall. His clinic-radiological features are described. PMID:26019426

  3. Basal ganglia correlates of fatigue in young adults

    PubMed Central

    Nakagawa, Seishu; Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Kotozaki, Yuka; Shinada, Takamitsu; Maruyama, Tsukasa; Sekiguchi, Atsushi; Iizuka, Kunio; Yokoyama, Ryoichi; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Miyauchi, Carlos Makoto; Magistro, Daniele; Sakaki, Kohei; Jeong, Hyeonjeong; Sasaki, Yukako; Kawashima, Ryuta

    2016-01-01

    Although the prevalence of chronic fatigue is approximately 20% in healthy individuals, there are no studies of brain structure that elucidate the neural correlates of fatigue outside of clinical subjects. We hypothesized that fatigue without evidence of disease might be related to changes in the basal ganglia and prefrontal cortex and be implicated in fatigue with disease. We aimed to identify the white matter structures of fatigue in young subjects without disease using magnetic resonance imaging (MRI). Healthy young adults (n = 883; 489 males and 394 females) were recruited. As expected, the degrees of fatigue and motivation were associated with larger mean diffusivity (MD) in the right putamen, pallidus and caudate. Furthermore, the degree of physical activity was associated with a larger MD only in the right putamen. Accordingly, motivation was the best candidate for widespread basal ganglia, whereas physical activity might be the best candidate for the putamen. A plausible mechanism of fatigue may involve abnormal function of the motor system, as well as areas of the dopaminergic system in the basal ganglia that are associated with motivation and reward. PMID:26893077

  4. Anti-basal ganglia antibodies in PANDAS.

    PubMed

    Singer, Harvey S; Loiselle, Christopher R; Lee, Olivia; Minzer, Karen; Swedo, Susan; Grus, Franz H

    2004-04-01

    An autoimmune-mediated mechanism involving molecular mimicry has been proposed for a variety of pediatric movement disorders that occur after a streptococcal infection. In this study, anti-basal ganglia antibodies (ABGA) were measured in 15 children with the diagnosis of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and compared with those in 15 controls. ELISA and Western immunoblotting (WB) methods were used to detect ABGA against supernatant (S1), pellet (P2), and synaptosomal preparations from adult postmortem caudate, putamen, and globus pallidus. ELISA optical density values did not differ between PANDAS patients and controls across all preparations. Immunoblotting identified multiple bands in all subjects with no differences in the number of bands or their total density. Discriminant analysis, used to assess mean binding patterns, showed that PANDAS patients differed from controls only for the caudate S1 fraction (Wilks' lambda = 0.0236, P < 0.0002), with PANDAS-primarily tic subjects providing the greatest discrimination. Among the epitopes contributing to differences between PANDAS and control in the caudate S1 fraction, mean binding to the epitope at 183 kDa was the most different between groups. In conclusion, ELISA measurements do not differentiate between PANDAS and controls, suggesting a lack of major antibody changes in this disorder. Further immunoblot analyses using a caudate supernatant fraction are required to completely exclude the possibility of minor antibody repertoire differences in PANDAS subjects, especially in those who primarily have tics. PMID:15077238

  5. 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

    2014-08-01

    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. PMID:24954674

  6. The basal ganglia-circa 1982 - A review and commentary

    NASA Technical Reports Server (NTRS)

    Mehler, W. R.

    1981-01-01

    A review is presented of recent studies which utilize new anterograde and retrograde axon transport methods in order to improve knowledge of the projection of the basal ganglia and to clarify their sites of origin. These studies have thrown new light on certain topographic connectional relationships and have revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Also examined are the many new histochemical techniques that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in or interconnecting with the basal ganglia.

  7. The Basal Ganglia as a Substrate for the Multiple Actions of Amphetamines

    PubMed Central

    Natarajan, Reka; Yamamoto, Bryan K.

    2011-01-01

    Amphetamines are psychostimulant drugs with high abuse potential. Acute and chronic doses of amphetamines affect dopamine (DA) neurotransmission in the basal ganglia. The basal ganglia are a group of subcortical nuclei that are anatomically positioned to integrate cognitive, motor and sensorimotor inputs from the cortex. Amphetamines can differentially alter the functioning of specific BG circuits to produce neurochemical changes that affect cognition, movement, and drug seeking behavior through their effects on DA neurotransmission. This review focuses on how alterations in dopaminergic neurotransmission within distinct basal ganglia pathways can modify their functional output to predict and explain the acute and long term behavioral consequences of amphetamine exposure. PMID:21804952

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

    PubMed

    Kim, Hyoung F; Hikosaka, Okihide

    2015-07-01

    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

  9. Short latency cerebellar modulation of the basal ganglia

    PubMed Central

    Chen, Christopher H.; Fremont, Rachel; Arteaga-Bracho, Eduardo E.; Khodakhah, Kamran

    2014-01-01

    The graceful, purposeful motion of our body is an engineering feat which remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time. Here we show in mice that the cerebellum rapidly modulates the activity of the striatum via a disynaptic pathway. Under physiological conditions this short latency pathway is capable of facilitating optimal motor control by allowing the basal ganglia to incorporate time-sensitive cerebellar information and by guiding the sign of cortico-striatal plasticity. Conversely, under pathological condition this pathway relays aberrant cerebellar activity to the basal ganglia to cause dystonia. PMID:25402853

  10. Genetics Home Reference: familial idiopathic basal ganglia calcification

    MedlinePlus

    ... in regulating phosphate levels within the body (phosphate homeostasis) by transporting phosphate across cell membranes. The SLC20A2 ... link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet. 2012 Feb 12;44(3):254- ...

  11. Short latency cerebellar modulation of the basal ganglia.

    PubMed

    Chen, Christopher H; Fremont, Rachel; Arteaga-Bracho, Eduardo E; Khodakhah, Kamran

    2014-12-01

    The graceful, purposeful motion of our body is an engineering feat that remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow, multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time. We found that the cerebellum rapidly modulates the activity of the striatum via a disynaptic pathway in mice. Under physiological conditions, this short latency pathway was capable of facilitating optimal motor control by allowing the basal ganglia to incorporate time-sensitive cerebellar information and by guiding the sign of cortico-striatal plasticity. Conversely, under pathological condition, this pathway relayed aberrant cerebellar activity to the basal ganglia to cause dystonia. PMID:25402853

  12. Disruption of automatic speech following a right basal ganglia lesion.

    PubMed

    Speedie, L J; Wertman, E; Ta'ir, J; Heilman, K M

    1993-09-01

    Following a right basal ganglia lesion, a right-handed man, age 75, was unable to recite familiar verses. Serial automatic speech, singing, recitation of rhymes, and swearing were impaired, and only idioms and social greetings were preserved. Speech no longer contained overused phrases and he could comprehend automatic speech. In contrast, propositional speech was preserved in both French and Hebrew. Right basal ganglia lesions may impair production but not comprehension of automatic speech. PMID:8414029

  13. The basal ganglia within a cognitive system in birds and mammals.

    PubMed

    Petkov, Christopher I; Jarvis, Erich D

    2014-12-01

    The primate basal ganglia are fundamental to Ackermann et al.'s proposal. However, primates and rodents are models for human cognitive functions involving basal ganglia circuits, and links between striatal function and vocal communication come from songbirds. We suggest that the proposal is better integrated in cognitive and/or motor theories on spoken language origins and with more analogous nonhuman animal models. PMID:25514958

  14. Anatomy of a songbird basal ganglia circuit essential for vocal learning and plasticity

    PubMed Central

    Gale, Samuel D.; Perkel, David J.

    2009-01-01

    Vocal learning in songbirds requires an anatomically discrete and functionally dedicated circuit called the anterior forebrain pathway (AFP). The AFP is homologous to cortico-basal ganglia-thalamo-cortical loops in mammals. The basal ganglia portion of this pathway, Area X, shares many features characteristic of the mammalian striatum and pallidum, including cell-types and connectivity. The AFP also deviates from mammalian basal ganglia circuits in fundamental ways. In addition, the microcircuitry, role of neuromodulators, and function of Area X are still unclear. Elucidating the mechanisms by which both mammalian-like and unique features of the AFP contribute to vocal learning may help lead to a broad understanding of the sensorimotor functions of basal ganglia circuits. PMID:19596062

  15. Basal Ganglia Subcircuits Distinctively Encode the Parsing and Concatenation of Action Sequences

    PubMed Central

    Jin, Xin; Tecuapetla, Fatuel; Costa, Rui M

    2014-01-01

    Chunking allows the brain to efficiently organize memories and actions. Although basal ganglia circuits have been implicated in action chunking, little is known about how individual elements are concatenated into a behavioral sequence at the neural level. Using a task where mice learn rapid action sequences, we uncovered neuronal activity encoding entire sequences as single actions in basal ganglia circuits. Besides start/stop activity signaling sequence parsing, we found neurons displaying inhibited or sustained activity throughout the execution of an entire sequence. This sustained activity covaried with the rate of execution of individual sequence elements, consistent with motor concatenation. Direct and indirect pathways of basal ganglia were concomitantly active during sequence initiation, but behaved differently during sequence performance, revealing a more complex functional organization of these circuits than previously postulated. These results have important implications for understanding the functional organization of basal ganglia during the learning and execution of action sequences. PMID:24464039

  16. 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

  17. Basal ganglia output reflects internally-specified movements

    PubMed Central

    Lintz, Mario J; Felsen, Gidon

    2016-01-01

    How movements are selected is a fundamental question in systems neuroscience. While many studies have elucidated the sensorimotor transformations underlying stimulus-guided movements, less is known about how internal goals – critical drivers of goal-directed behavior – guide movements. The basal ganglia are known to bias movement selection according to value, one form of internal goal. Here, we examine whether other internal goals, in addition to value, also influence movements via the basal ganglia. We designed a novel task for mice that dissociated equally rewarded internally-specified and stimulus-guided movements, allowing us to test how each engaged the basal ganglia. We found that activity in the substantia nigra pars reticulata, a basal ganglia output, predictably differed preceding internally-specified and stimulus-guided movements. Incorporating these results into a simple model suggests that internally-specified movements may be facilitated relative to stimulus-guided movements by basal ganglia processing. DOI: http://dx.doi.org/10.7554/eLife.13833.001 PMID:27377356

  18. Actor-critic models of the basal ganglia: new anatomical and computational perspectives.

    PubMed

    Joel, Daphna; Niv, Yael; Ruppin, Eytan

    2002-01-01

    A large number of computational models of information processing in the basal ganglia have been developed in recent years. Prominent in these are actor-critic models of basal ganglia functioning, which build on the strong resemblance between dopamine neuron activity and the temporal difference prediction error signal in the critic, and between dopamine-dependent long-term synaptic plasticity in the striatum and learning guided by a prediction error signal in the actor. We selectively review several actor-critic models of the basal ganglia with an emphasis on two important aspects: the way in which models of the critic reproduce the temporal dynamics of dopamine firing, and the extent to which models of the actor take into account known basal ganglia anatomy and physiology. To complement the efforts to relate basal ganglia mechanisms to reinforcement learning (RL), we introduce an alternative approach to modeling a critic network, which uses Evolutionary Computation techniques to 'evolve' an optimal RL mechanism, and relate the evolved mechanism to the basic model of the critic. We conclude our discussion of models of the critic by a critical discussion of the anatomical plausibility of implementations of a critic in basal ganglia circuitry, and conclude that such implementations build on assumptions that are inconsistent with the known anatomy of the basal ganglia. We return to the actor component of the actor-critic model, which is usually modeled at the striatal level with very little detail. We describe an alternative model of the basal ganglia which takes into account several important, and previously neglected, anatomical and physiological characteristics of basal ganglia-thalamocortical connectivity and suggests that the basal ganglia performs reinforcement-biased dimensionality reduction of cortical inputs. We further suggest that since such selective encoding may bias the representation at the level of the frontal cortex towards the selection of rewarded

  19. Synchronizing activity of basal ganglia and pathophysiology of Parkinson's disease.

    PubMed

    Heimer, G; Rivlin, M; Israel, Z; Bergman, H

    2006-01-01

    Early physiological studies emphasized changes in the discharge rate of basal ganglia in the pathophysiology of Parkinson's disease (PD), whereas recent studies stressed the role of the abnormal oscillatory activity and neuronal synchronization of pallidal cells. However, human observations cast doubt on the synchronization hypothesis since increased synchronization may be an epi-phenomenon of the tremor or of independent oscillators with similar frequency. Here, we show that modern actor/ critic models of the basal ganglia predict the emergence of synchronized activity in PD and that significant non-oscillatory and oscillatory correlations are found in MPTP primates. We conclude that the normal fluctuation of basal ganglia dopamine levels combined with local cortico-striatal learning rules lead to noncorrelated activity in the pallidum. Dopamine depletion, as in PD, results in correlated pallidal activity, and reduced information capacity. We therefore suggest that future deep brain stimulation (DBS) algorithms may be improved by desynchronizing pallidal activity. PMID:17017503

  20. 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…

  1. Exercise-induced changes in basal ganglia volume and cognition in older adults.

    PubMed

    Niemann, C; Godde, B; Staudinger, U M; Voelcker-Rehage, C

    2014-12-01

    Physical activity has been demonstrated to diminish age-related brain volume shrinkage in several brain regions accompanied by a reduction of age-related decline in cognitive functions. Most studies investigated the impact of cardiovascular fitness or training. Other types of fitness or training are less well investigated. In addition, little is known about exercise effects on volume of the basal ganglia, which, however, are involved in motor activities and cognitive functioning. In the current study (1) we examined the relationships of individual cardiovascular and motor fitness levels with the volume of the basal ganglia (namely caudate, putamen, and globus pallidus) and selected cognitive functions (executive control, perceptual speed). (2) We investigated the effect of 12-month training interventions (cardiovascular and coordination training, control group stretching and relaxation) on the volume of the respective basal ganglia nuclei. Results revealed that motor fitness but not cardiovascular fitness was positively related with the volume of the putamen and the globus pallidus. Additionally, a moderating effect of the volume of the basal ganglia (as a whole, but also separately for putamen and globus pallidus) on the relationship between motor fitness and executive function was revealed. Coordination training increased caudate and globus pallidus volume. We provide evidence that coordinative exercise seems to be a favorable leisure activity for older adults that has the potential to improve volume of the basal ganglia. PMID:25255932

  2. Mephedrone alters basal ganglia and limbic neurotensin systems

    PubMed Central

    German, Christopher L.; Hoonakker, Amanda H.; Fleckenstein, Annette E.; Hanson, Glen R.

    2014-01-01

    Mephedrone (4-methylmethcathinone) is a synthetic cathinone designer drug that alters presynaptic dopamine (DA) activity like many psychostimulants. However, little is known about the postsynaptic dopaminergic impacts of mephedrone. The neuropeptide neurotensin (NT) provides inhibitory feedback for basal ganglia and limbic DA pathways, and postsynaptic D1-like and D2-like receptor activity affects NT tissue levels. This study evaluated how mephedrone alters basal ganglia and limbic system NT content and the role of NT receptor activation in drug consumption behavior. Four 25 mg/kg injections of mephedrone increased NT content in basal ganglia (striatum, substantia nigra and globus pallidus) and the limbic regions (nucleus accumbens core), while a lower dosage (5 mg/kg/injection) only increased striatal NT content. Mephedrone-induced increases in basal ganglia NT levels were mediated by D1-like receptors in the striatum and the substantia nigra by both D1-like and D2-like receptors in the globus pallidus. Mephedrone increased substance P content, another neuropeptide, in the globus pallidus, but not in the dorsal striatum or substantia nigra. Finally, the NT receptor agonist PD149163 blocked mephedrone self-administration, suggesting reduced NT release, as indicated by increased tissue levels, likely contributing to patterns of mephedrone consumption. PMID:24678634

  3. Basal ganglia morphology links the metabolic syndrome and depressive symptoms

    PubMed Central

    Onyewuenyi, Ikechukwu C.; Muldoon, Matthew F.; Christie, Israel C.; Erickson, Kirk I.; Gianaros, Peter J.

    2014-01-01

    The metabolic syndrome (MetS) is a clustering of cardiovascular and cerebrovascular risk factors that are often comorbid with depressive symptoms. Individual components of the MetS also covary with the morphology of basal ganglia regions that are altered by depression. However, it remains unknown whether the covariation between the MetS and depressive symptomatology can be accounted for in part by morphological changes in the basal ganglia. Accordingly, we tested the hypothesis that increased depressive symptoms among individuals with the MetS might be statistically mediated by reduced grey matter volume in basal ganglia regions. The presence of the MetS was determined in 147 middle-aged adults using the criteria of the National Cholesterol Education Program, Adult Treatment Panel III. Basal ganglia volumes were determined on an a priori basis by automated segmentation of high-resolution magnetic resonance images. Depressive symptoms were assessed using the Patient Health Questionnaire. Even after controlling for demographic and other confounding factors, having the MetS and meeting more MetS criteria covaried with reduced globus pallidus volume. Meeting more MetS criteria and reduced pallidal volume were also related to depressive symptoms. Moreover, the MetS-depression association was statistically mediated by pallidal volume. In summary, reduced globus pallidus volume is a neural correlate of the MetS that may partly account for its association with depressive symptoms. PMID:24096008

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

    MedlinePlus

    ... 4 links) Encyclopedia: Basal Ganglia Dysfunction Health Topic: B Vitamins Health Topic: Brain Diseases Health Topic: Movement Disorders ... doi: 10.1055/s-0028-1128152. Epub 2009 Mar 17. Review. Citation on PubMed GeneReview: Biotin-Thiamine-Responsive ...

  5. 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.

  6. A neural model of basal ganglia-thalamocortical relations in normal and parkinsonian movement.

    PubMed

    Contreras-Vidal, J L; Stelmach, G E

    1995-10-01

    Anatomical, neurophysiological, and neurochemical evidence supports the notion of parallel basal ganglia-thalamocortical motor systems. We developed a neural network model for the functioning of these systems during normal and parkinsonian movement. Parkinson's disease (PD), which results predominantly from nigrostriatal pathway damage, is used as a window to examine basal ganglia function. Simulations of dopamine depletion produce motor impairments consistent with motor deficits observed in PD that suggest the basal ganglia play a role in motor initiation and execution, and sequencing of motor programs. Stereotaxic lesions in the model's globus pallidus and subthalamic nucleus suggest that these lesions, although reducing some PD symptoms, may constrain the repertoire of available movements. It is proposed that paradoxical observations of basal ganglia responses reported in the literature may result from regional functional neuronal specialization, and the non-uniform distributions of neurochemicals in the basal ganglia. It is hypothesized that dopamine depletion produces smaller-than-normal pallidothalamic gating signals that prevent rescalability of these signals to control variable movement speed, and that in PD can produce smaller-than-normal movement amplitudes. PMID:7578481

  7. Bilateral basal ganglia activation associated with sensorimotor adaptation.

    PubMed

    Seidler, R D; Noll, D C; Chintalapati, P

    2006-11-01

    Sensorimotor adaptation tasks can be classified into two types. When subjects adapt movements to visual feedback perturbations such as in prism lens adaptation, they perform kinematic adaptations. When subjects adapt movements to force field perturbations such as with robotic manipulanda, they perform kinetic adaptations. Neuroimaging studies have shown basal ganglia involvement in kinetic adaptations, but have found little evidence of basal ganglia involvement in kinematic adaptations, despite reports of deficits in patients with diseases of the basal ganglia, such as Parkinson's and Huntington's disease, in these. In an effort to resolve such apparent discrepancy, we used FMRI to focus on the first few minutes of practice during kinematic adaptation. Human subjects adapted to visuomotor rotations in the context of a joystick aiming task while lying supine in a 3.0 T MRI scanner. As demonstrated previously, early adaptive processes were associated with BOLD activation in the cerebellum and the sensory and motor cortical regions. A novel finding of this study was bilateral basal ganglia activation. This suggests that, at least for early learning, the neural correlates of kinematic adaptation parallel those of other types of skill learning. We observed activation in the right globus pallidus and putamen, along with the right prefrontal, premotor and parietal cortex, which may support spatial cognitive processes of adaptation. We also observed activation in the left globus pallidus and caudate nucleus, along with the left premotor and supplementary motor cortex, which may support the sensorimotor processes of adaptation. These results are the first to demonstrate a clear involvement of basal ganglia activation in this type of kinematic motor adaptation. PMID:16794848

  8. Basal Ganglia Plus Insula Damage Yields Stronger Disruption of Smoking Addiction Than Basal Ganglia Damage Alone

    PubMed Central

    2014-01-01

    Introduction: The main objective of this study was to elucidate the importance of the basal ganglia (BG) and insula (INS) for nicotine addiction and smoking behavior. Methods: We used a lesion study examining the effects of BG and INS damage on changes in smoking behavior and nicotine dependence over time in a prospective manner. We studied whether combined BG and INS damage yields more substantial disruption of smoking and nicotine dependence than damage to the BG alone and compared with damage to other brain regions outside the BG and INS (brain-damaged comparison [BDC] group). We obtained neuroanatomical and behavioral data for 63 neurological patients with stroke at 1 month after onset and at 3-, 6-, and 12-month follow-ups. All patients were smokers at lesion onset. Results: The BG and BG + INS groups had significantly higher and more sustained rates of smoking cessation than patients with damage elsewhere. By 12 months after onset, only 14.3% of the patients in the BDC group were classified as nonsmokers. In the BG group, 37% were not smoking by the 12-month follow-up, and in the BG + INS group, smoking cessation was even more pronounced, as 75% of this group was not smoking at the 12-month epoch. Conclusions: The findings show that damage to the BG alone can cause disruption of smoking addiction, and when BG damage is combined with INS damage, the disruption increases. The latter finding is consistent with the proposal that the INS has a key role in smoking addiction. PMID:24169814

  9. What do the basal ganglia do? A modeling perspective.

    PubMed

    Chakravarthy, V S; Joseph, Denny; Bapi, Raju S

    2010-09-01

    Basal ganglia (BG) constitute a network of seven deep brain nuclei involved in a variety of crucial brain functions including: action selection, action gating, reward based learning, motor preparation, timing, etc. In spite of the immense amount of data available today, researchers continue to wonder how a single deep brain circuit performs such a bewildering range of functions. Computational models of BG have focused on individual functions and fail to give an integrative picture of BG function. A major breakthrough in our understanding of BG function is perhaps the insight that activities of mesencephalic dopaminergic cells represent some form of 'reward' to the organism. This insight enabled application of tools from 'reinforcement learning,' a branch of machine learning, in the study of BG function. Nevertheless, in spite of these bright spots, we are far from the goal of arriving at a comprehensive understanding of these 'mysterious nuclei.' A comprehensive knowledge of BG function has the potential to radically alter treatment and management of a variety of BG-related neurological disorders (Parkinson's disease, Huntington's chorea, etc.) and neuropsychiatric disorders (schizophrenia, obsessive compulsive disorder, etc.) also. In this article, we review the existing modeling literature on BG and hypothesize an integrative picture of the function of these nuclei. PMID:20644953

  10. Dopaminergic Control of the Exploration-Exploitation Trade-Off via the Basal Ganglia

    PubMed Central

    Humphries, Mark D.; Khamassi, Mehdi; Gurney, Kevin

    2012-01-01

    We continuously face the dilemma of choosing between actions that gather new information or actions that exploit existing knowledge. This “exploration-exploitation” trade-off depends on the environment: stability favors exploiting knowledge to maximize gains; volatility favors exploring new options and discovering new outcomes. Here we set out to reconcile recent evidence for dopamine’s involvement in the exploration-exploitation trade-off with the existing evidence for basal ganglia control of action selection, by testing the hypothesis that tonic dopamine in the striatum, the basal ganglia’s input nucleus, sets the current exploration-exploitation trade-off. We first advance the idea of interpreting the basal ganglia output as a probability distribution function for action selection. Using computational models of the full basal ganglia circuit, we showed that, under this interpretation, the actions of dopamine within the striatum change the basal ganglia’s output to favor the level of exploration or exploitation encoded in the probability distribution. We also found that our models predict striatal dopamine controls the exploration-exploitation trade-off if we instead read-out the probability distribution from the target nuclei of the basal ganglia, where their inhibitory input shapes the cortical input to these nuclei. Finally, by integrating the basal ganglia within a reinforcement learning model, we showed how dopamine’s effect on the exploration-exploitation trade-off could be measurable in a forced two-choice task. These simulations also showed how tonic dopamine can appear to affect learning while only directly altering the trade-off. Thus, our models support the hypothesis that changes in tonic dopamine within the striatum can alter the exploration-exploitation trade-off by modulating the output of the basal ganglia. PMID:22347155

  11. Proceedings of a symposium on the neurobiology of the basal ganglia. Glasgow, United Kingdom, July 1999.

    PubMed

    2000-05-01

    Glasgow University in July 1999 as part of the Summer Meeting of the Anatomical Society of Great Britain and Ireland. The invited speakers were chosen to be wide ranging and contributions encompassed evolution, circuitry and receptors of the basal ganglia, striatal remodelling after dopamine loss, striatal functioning in humans with Huntington's disease and in primate models after midbrain fetal transplants, and the genetics of basal ganglia disorders. Short presentations and posters of current results supplemented the main presentations and some are also included amongst these reviews. PMID:10960285

  12. Neuropsychological impairment after hemorrhagic stroke in basal ganglia.

    PubMed

    Su, Chwen-Yng; Chen, Hui-Mei; Kwan, Aij-Lie; Lin, Yueh-Hsieh; Guo, Nai-Wen

    2007-05-01

    We aimed to determine the severity and pattern of cognitive dysfunction in patients with basal ganglia (BG) hemorrhage within the first 6 months after stroke and to identify its clinical correlates. The study samples consisted of 30 patients with BG hemorrhage and 37 healthy controls. A comprehensive neuropsychological battery including tests of attention, memory, language, visuospatial function, and executive function was administered to all participants. Relative to healthy controls, BG patients performed significantly worse across different cognitive domains after controlling for age, sex, and education. 96.7% of patients displayed defective performance on at least three neuropsychological tests. Discriminant function analysis showed that visuospatial function and memory were the best predictors of group membership (patient/control), with an overall classification rate of 95.5%. Only side of stroke and admission Glasgow Coma Scale (GCS) score correlated significantly with some of the cognitive domains. The widespread pattern of cognitive deficits seen in BG patients provides evidence for the substantial involvement of the BG in many neuronal pathways connecting cortical and subcortical brain areas responsible for various cognitive functions. PMID:17336034

  13. Basal Ganglia Shapes Predict Social, Communication, and Motor Dysfunctions in Boys with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Qiu, Anqi; Adler, Marcy; Crocetti, Deana; Miller, Michael I.; Mostofsky, Stewart H.

    2010-01-01

    Objective: Basal ganglia abnormalities have been suggested as contributing to motor, social, and communicative impairments in autism spectrum disorder (ASD). Volumetric analyses offer limited ability to detect localized differences in basal ganglia structure. Our objective was to investigate basal ganglia shape abnormalities and their association…

  14. The role of the basal ganglia in beat perception: neuroimaging and neuropsychological investigations.

    PubMed

    Grahn, Jessica A

    2009-07-01

    Perception of musical rhythms is culturally universal. Despite this special status, relatively little is known about the neurobiology of rhythm perception, particularly with respect to beat processing. Findings are presented here from a series of studies that have specifically examined the neural basis of beat perception, using functional magnetic resonance imaging (fMRI) and studying patients with Parkinson's disease. fMRI data indicate that novel beat-based sequences robustly activate the basal ganglia when compared to irregular, nonbeat sequences. Furthermore, although most healthy participants find it much easier to discriminate changes in beat-based sequences compared to irregular sequences, Parkinson's disease patients fail to show the same degree of benefit. Taken together, these data suggest that the basal ganglia are performing a crucial function in beat processing. The results of an additional fMRI study indicate that the role of the basal ganglia is strongly linked to internal generation of the beat. Basal ganglia activity is greater when participants listen to rhythms in which internal generation of the beat is required, as opposed to rhythms with strongly externally cued beats. Functional connectivity between part of the basal ganglia (the putamen) and cortical motor areas (premotor and supplementary motor areas) is also higher during perception of beat rhythms compared to nonbeat rhythms. Increased connectivity between cortical motor and auditory areas is found in those with musical training. The findings from these converging methods strongly implicate the basal ganglia in processing a regular beat, particularly when internal generation of the beat is required. PMID:19673753

  15. Cognition and the basal ganglia: a possible substrate for procedural knowledge.

    PubMed

    Phillips, A G; Carr, G D

    1987-08-01

    Disruption of neural activity within the basal ganglia of experimental animals causes selective learning deficits in tasks requiring switching between response strategies. These data along with reports of both general and specific intellectual impairment in patients with neurodegenerative disorders such as Parkinson's disease, appear to support the theory of cognitive functions of the basal ganglia. Recent studies have failed to confirm general cognitive or memory deficits in parkinsonian patients, but have identified deficiencies in devising and executing certain cognitive strategies. Following the lead of theorists such as Squire and Mishkin, this brief review emphasizes the distinction between procedural and declarative knowledge and examines the possible role of the basal ganglia in the acquisition and retention of procedural knowledge. PMID:3315145

  16. 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

  17. Morphological elucidation of basal ganglia circuits contributing reward prediction.

    PubMed

    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

  18. [Morphological Re-evaluation of the Basal Ganglia Network].

    PubMed

    Fujiyama, Fumino

    2016-07-01

    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 dopamine signals, via dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of reward prediction error and conducts 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, with particular focus on the striosome and matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome and matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. PMID:27395470

  19. Neural representation of time in cortico-basal ganglia circuits

    PubMed Central

    Jin, Dezhe Z.; Fujii, Naotaka; Graybiel, Ann M.

    2009-01-01

    Encoding time is universally required for learning and structuring motor and cognitive actions, but how the brain keeps track of time is still not understood. We searched for time representations in cortico-basal ganglia circuits by recording from thousands of neurons in the prefrontal cortex and striatum of macaque monkeys performing a routine visuomotor task. We found that a subset of neurons exhibited time-stamp encoding strikingly similar to that required by models of reinforcement-based learning: They responded with spike activity peaks that were distributed at different time delays after single task events. Moreover, the temporal evolution of the population activity allowed robust decoding of task time by perceptron models. We suggest that time information can emerge as a byproduct of event coding in cortico-basal ganglia circuits and can serve as a critical infrastructure for behavioral learning and performance. PMID:19850874

  20. MRI of germinomas arising from the basal ganglia and thalamus.

    PubMed

    Kim, D I; Yoon, P H; Ryu, Y H; Jeon, P; Hwang, G J

    1998-08-01

    We reviewed the MRI findings of germinomas originating from the basal ganglia, thalamus or deep white matter in 13 patients with 14 germinomas, excluding those in the suprasellar or pineal regions. Ten cases were confirmed as germinomas by stereotaxic biopsy, three by partial and one by total removal of the tumour. Analysis was focussed on the location and the signal characteristic of the tumour, haemorrhage, cysts within the tumour and any other associated findings. Thirteen of the tumours were in the basal ganglia and one in the thalamus. Haemorrhage was observed in seven patients, while twelve showed multiple cysts. Associated ipsilateral cerebral hemiatrophy was seen in three patients. The signal intensity of the parenchymal germinomas was heterogeneous on T1- and T2-weighted images due to haemorrhage, cysts and solid portions. We also report the MRI findings of germinomas in an early stage in two patients. PMID:9763338

  1. Pure psychic akinesia with bilateral lesions of basal ganglia.

    PubMed Central

    Laplane, D; Baulac, M; Widlöcher, D; Dubois, B

    1984-01-01

    Three patients showed dramatic psychic akinesia after recovery from toxic encephalopathy. They had no or only mild motor disorders. The spontaneous psychic akinesia was reversible when the patient was stimulated, as if there was a loss of self psychic activation. Intellectual capacities were normal. Two patients had stereotyped behaviours resembling compulsions. In all patients CT cans showed bilateral lesions in the basal ganglia, mainly within the globus pallidus. Images PMID:6726263

  2. Movement Disorders Following Cerebrovascular Lesion in the Basal Ganglia Circuit.

    PubMed

    Park, Jinse

    2016-05-01

    Movement disorders are primarily associated with the basal ganglia and the thalamus; therefore, movement disorders are more frequently manifest after stroke compared with neurological injuries associated with other structures of the brain. Overall clinical features, such as types of movement disorder, the time of onset and prognosis, are similar with movement disorders after stroke in other structures. Dystonia and chorea are commonly occurring post-stroke movement disorders in basal ganglia circuit, and these disorders rarely present with tremor. Rarer movement disorders, including tic, restless leg syndrome, and blepharospasm, can also develop following a stroke. Although the precise mechanisms underlying the pathogenesis of these conditions have not been fully characterized, disruptions in the crosstalk between the inhibitory and excitatory circuits resulting from vascular insult are proposed to be the underlying cause. The GABA (gamma-aminobutyric acid)ergic and dopaminergic systems play key roles in post-stroke movement disorders. This review summarizes movement disorders induced by basal ganglia and thalamic stroke according to the anatomical regions in which they manifest. PMID:27240808

  3. Autoimmunity and the basal ganglia: new insights into old diseases.

    PubMed

    Dale, R C

    2003-03-01

    Sydenham's chorea (SC) occurs weeks or months after Group A streptococcal infection, and is characterized by involuntary, purposeless movements of the limbs, in addition to behavioural alteration. There is a body of evidence which suggests that SC is an immune-mediated brain disorder with regional localization to the basal ganglia. Recent reports have suggested that the spectrum of post-streptococcal CNS disease is broader than chorea alone, and includes other hyperkinetic movement disorders (tics, dystonia and myoclonus). In addition, there are high rates of behavioural sequelae, particularly emotional disorders such as obsessive-compulsive disorder, anxiety and depression. These findings have lead to the hypothesis that similar immune-mediated basal ganglia processes may be operating in common neuropsychiatric disease such as tic disorders, Tourette syndrome and obsessive-compulsive disorder. This review analyses the historical aspects of post-streptococcal CNS disease, and the recent immunological studies which have addressed the hypothesis that common neuropsychiatric disorders may be secondary to basal ganglia autoimmunity. PMID:12615982

  4. Neuroimaging in basal ganglia disorders: perspectives for transcranial ultrasound.

    PubMed

    Becker, G; Berg, D

    2001-01-01

    Transcranial sonography is a new diagnostic tool, allowing not only the evaluation of cerebral arteries but also the two-dimensional display of the brain parenchyma. In this review we will summarize basics of the application, the ultrasound anatomy of the brain and sonographic findings in some movement disorders. While in normal adults basal ganglia nuclei are hypoechogenic, they are hyperechogenic in certain basal ganglia disorders. In Parkinson's disease, for example, the substantia nigra can be depicted as a distinctly echogenic area. An elevated echogenicity of the lentiform nuclei was noticed in patients with primary adult-onset dystonia. In both disorders the altered echogenicity may arise from higher heavy metal tissue content (i.e. iron in Parkinson's disease and copper in primary dystonia). Our findings converge to the hypothesis that transcranial ultrasound sensitively detects pathological metal accumulation not identified by other neuroimaging techniques (CT and MRI) and therefore provides new insights in the diagnosis of basal ganglia disorders. The implications of these findings for the understanding of the pathogenesis and its usefulness for the early diagnosis of movement disorders are outlined. PMID:11215589

  5. Movement Disorders Following Cerebrovascular Lesion in the Basal Ganglia Circuit

    PubMed Central

    Park, Jinse

    2016-01-01

    Movement disorders are primarily associated with the basal ganglia and the thalamus; therefore, movement disorders are more frequently manifest after stroke compared with neurological injuries associated with other structures of the brain. Overall clinical features, such as types of movement disorder, the time of onset and prognosis, are similar with movement disorders after stroke in other structures. Dystonia and chorea are commonly occurring post-stroke movement disorders in basal ganglia circuit, and these disorders rarely present with tremor. Rarer movement disorders, including tic, restless leg syndrome, and blepharospasm, can also develop following a stroke. Although the precise mechanisms underlying the pathogenesis of these conditions have not been fully characterized, disruptions in the crosstalk between the inhibitory and excitatory circuits resulting from vascular insult are proposed to be the underlying cause. The GABA (gamma-aminobutyric acid)ergic and dopaminergic systems play key roles in post-stroke movement disorders. This review summarizes movement disorders induced by basal ganglia and thalamic stroke according to the anatomical regions in which they manifest. PMID:27240808

  6. Observation of sonified movements engages a basal ganglia frontocortical network

    PubMed Central

    2013-01-01

    Background Producing sounds by a musical instrument can lead to audiomotor coupling, i.e. the joint activation of the auditory and motor system, even when only one modality is probed. The sonification of otherwise mute movements by sounds based on kinematic parameters of the movement has been shown to improve motor performance and perception of movements. Results Here we demonstrate in a group of healthy young non-athletes that congruently (sounds match visual movement kinematics) vs. incongruently (no match) sonified breaststroke movements of a human avatar lead to better perceptual judgement of small differences in movement velocity. Moreover, functional magnetic resonance imaging revealed enhanced activity in superior and medial posterior temporal regions including the superior temporal sulcus, known as an important multisensory integration site, as well as the insula bilaterally and the precentral gyrus on the right side. Functional connectivity analysis revealed pronounced connectivity of the STS with the basal ganglia and thalamus as well as frontal motor regions for the congruent stimuli. This was not seen to the same extent for the incongruent stimuli. Conclusions We conclude that sonification of movements amplifies the activity of the human action observation system including subcortical structures of the motor loop. Sonification may thus be an important method to enhance training and therapy effects in sports science and neurological rehabilitation. PMID:23496827

  7. Basal ganglia contributions to adaptive navigation.

    PubMed

    Mizumori, Sheri J Y; Puryear, Corey B; Martig, Adria K

    2009-04-12

    The striatum has long been considered to be selectively important for nondeclarative, procedural types of memory. This stands in contrast with spatial context processing that is typically attributed to hippocampus. Neurophysiological evidence from studies of the neural mechanisms of adaptive navigation reveals that distinct neural systems such as the striatum and hippocampus continuously process task relevant information regardless of the current cognitive strategy. For example, both striatal and hippocampal neural representations reflect spatial location, directional heading, reward, and egocentric movement features of a test situation in an experience-dependent way, and independent of task demands. Thus, continual parallel processing across memory systems may be the norm rather than the exception. It is suggested that neuromodulators, such as dopamine, may serve to differentially regulate learning-induced neural plasticity mechanisms within these memory systems such that the most successful form of neural processing exerts the strongest control over response selection functions. In this way, dopamine may serve to optimize behavioral choices in the face of changing environmental demands during navigation. PMID:19056429

  8. Multiplexed coding in the human basal ganglia

    NASA Astrophysics Data System (ADS)

    Andres, D. S.; Cerquetti, D.; Merello, M.

    2016-04-01

    A classic controversy in neuroscience is whether information carried by spike trains is encoded by a time averaged measure (e.g. a rate code), or by complex time patterns (i.e. a time code). Here we apply a tool to quantitatively analyze the neural code. We make use of an algorithm based on the calculation of the temporal structure function, which permits to distinguish what scales of a signal are dominated by a complex temporal organization or a randomly generated process. In terms of the neural code, this kind of analysis makes it possible to detect temporal scales at which a time patterns coding scheme or alternatively a rate code are present. Additionally, finding the temporal scale at which the correlation between interspike intervals fades, the length of the basic information unit of the code can be established, and hence the word length of the code can be found. We apply this algorithm to neuronal recordings obtained from the Globus Pallidus pars interna from a human patient with Parkinson’s disease, and show that a time pattern coding and a rate coding scheme co-exist at different temporal scales, offering a new example of multiplexed neuronal coding.

  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. [Distinct roles of the direct and indirect pathways in the basal ganglia circuit mechanism].

    PubMed

    Morita, Makiko; Hikida, Takatoshi

    2015-11-01

    The basal ganglia are key neural substrates that control not only motor balance but also emotion, motivation, cognition, learning, and decision-making. Dysfunction of the basal ganglia leads to neurodegenerative diseases (e.g. Parkinson's disease and Huntington's disease) and psychiatric disorders (e.g. drug addiction, schizophrenia, and depression). In the basal ganglia circuit, there are two important pathways: the direct and indirect striatal pathways. Recently, new molecular techniques that activate or inactive selectively the direct or indirect pathway neurons have revealed the function of each pathway. Here we review the distinct roles of the direct and indirect striatal pathways in brain function and drug addiction. We have developed a reversible neurotransmission blocking technique, in which transmission of each pathway is selectively blocked by specific expression of transmission-blocking tetanus toxin, and revealed that the activation of D1 receptors in the direct pathway is critical for reward learning/cocaine addiction, and that the inactivation of D2 receptors is critical for aversive learning/learning flexibility. We propose a new circuit mechanism by which the dopaminergic input from the ventral tegmental area can switch the direct and indirect pathways in the nucleus accumbens. These basal ganglia circuit mechanisms will give us insights into the pathophysiology of mental diseases. PMID:26785520

  11. 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

  12. 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

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

    PubMed

    Yttri, Eric A; Dudman, Joshua T

    2016-05-19

    For goal-directed behaviour it is critical that we can both select the appropriate action and learn to modify the underlying movements (for example, 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 behaviour, such as the neocortex and thalamus, are integrated with reward signalling to reinforce successful, purposive actions. The 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 and suppress actions that do not, respectively. Activity-dependent plasticity modulated by reward is thought to be sufficient for selecting actions in the striatum. Although perturbations of basal ganglia function produce profound changes in movement, it remains unknown whether activity-dependent plasticity is sufficient to produce learned changes in movement kinematics, such as velocity. Here we use cell-type-specific stimulation in mice 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 behavioural 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

  14. Understanding Parkinsonian handwriting through a computational model of basal ganglia.

    PubMed

    Gangadhar, Garipelli; Joseph, Denny; Chakravarthy, V Srinivasa

    2008-10-01

    Handwriting in Parkinson's disease (PD) is typically characterized by micrographia, jagged line contour, and unusual fluctuations in pen tip velocity. Although PD handwriting features have been used for diagnostics, they are not based on a signaling model of basal ganglia (BG). In this letter, we present a computational model of handwriting generation that highlights the role of BG. When PD conditions like reduced dopamine and altered dynamics of the subthalamic nucleus and globus pallidus externa subsystems are simulated, the handwriting produced by the model manifested characteristic PD handwriting distortions like micrographia and velocity fluctuations. Our approach to PD modeling is in tune with the perspective that PD is a dynamic disease. PMID:18386983

  15. Hypotensive hemorrhagic necrosis in basal ganglia and brainstem.

    PubMed

    Opeskin, K; Burke, M P

    2000-12-01

    Hypotensive hemorrhagic necrosis of the basal ganglia and brainstem has only occasionally been described. Three such cases are reported. Cardiac arrest had occurred in all cases, and it took at least 1 hour to restore adequate circulation. The patients remained comatose for 2 days to 2 weeks until death. Persistent hypotension causing ischemia in the distribution of deep perforating arteries is considered to have been the key underlying mechanism. Hemorrhage is thought to have been caused by extravasation of red blood cells through damaged blood vessels. PMID:11111807

  16. Idiopathic Basal Ganglia Calcification Presented with Impulse Control Disorder

    PubMed Central

    Sahin, Cem; Levent, Mustafa; Akbaba, Gulhan; Kara, Bilge; Yeniceri, Emine Nese; Inanc, Betul Battaloglu

    2015-01-01

    Primary familial brain calcification (PFBC), also referred to as Idiopathic Basal Ganglia Calcification (IBGC) or “Fahr's disease,” is a clinical condition characterized by symmetric and bilateral calcification of globus pallidus and also basal ganglions, cerebellar nuclei, and other deep cortical structures. It could be accompanied by parathyroid disorder and other metabolic disturbances. The clinical features are dysfunction of the calcified anatomic localization. IBGC most commonly presents with mental damage, convulsion, parkinson-like clinical picture, and neuropsychiatric behavior disorders; however, presentation with impulse control disorder is not a frequent presentation. In the current report, a 43-year-old male patient who has been admitted to psychiatry policlinic with the complaints of aggressive behavior episodes and who has been diagnosed with impulse control disorder and IBGC was evaluated in the light of the literature. PMID:26246920

  17. 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

  18. Mephedrone alters basal ganglia and limbic dynorphin systems

    PubMed Central

    German, Christopher L.; Alburges, Mario E.; Hoonakker, Amanda J.; Fleckenstein, Annette E.; Hanson, Glen R.

    2014-01-01

    Mephedrone (4-methymethcathinone) is a synthetic cathinone designer drug that disrupts central nervous system (CNS) dopamine (DA) signaling. Numerous central neuropeptide systems reciprocally interact with dopaminergic neurons to provide regulatory counterbalance, and are altered by aberrant DA activity associated with stimulant exposure. Endogenous opioid neuropeptides are highly concentrated within dopaminergic CNS regions and facilitate many rewarding and aversive properties associated with drug use. Dynorphin, an opioid neuropeptide and kappa receptor agonist, causes dysphoria and aversion to drug consumption through signaling within the basal ganglia and limbic systems, which is affected by stimulants. This study evaluated how mephedrone alters basal ganglia and limbic system dynorphin content, and the role of DA signaling in these changes. Repeated mephedrone administrations (4 × 25 mg/kg/injection, 2-h intervals) selectively increased dynorphin content throughout the dorsal striatum and globus pallidus, decreased dynorphin content within the frontal cortex, and did not alter dynorphin content within most limbic system structures. Pre-treatment with D1-like (SCH-23380) or D2-like (eticlopride) antagonists blocked mephedrone-induced changes in dynorphin content in most regions examined, indicating altered dynorphin activity is a consequence of excessive DA signaling. PMID:25155699

  19. Familial idiopathic basal ganglia calcification (Fahr’s disease)

    PubMed Central

    Mufaddel, Amir A.; Al-Hassani, Ghanem A.

    2014-01-01

    Familial idiopathic basal ganglia calcification (Fahr’s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr’s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsychiatric features and movement disorders. Psychiatric features reported in the literature include: cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, schizophrenia-like psychosis, and personality change. Other clinical features include: Parkinsonism, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis. Fahr’s disease should be considered in the differential diagnosis of psychiatric symptoms, particularly when associated with movement disorder. The disease should be differentiated from other conditions that can cause intracranial calcification. No specific treatment is currently available. Further research is needed to bridge the gap existing in our current knowledge of the prevalence, etiology, symptoms, and treatment of Fahr’s disease. PMID:24983277

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

    PubMed Central

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

    2014-01-01

    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 the 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. PMID:24957866

  1. Balancing the Basal Ganglia Circuitry: A Possible New Role for Dopamine D2 Receptors in Health and Disease

    PubMed Central

    Cazorla, Maxime; Kang, Un Jung; Kellendonk, Christoph

    2016-01-01

    Current therapies for treating movement disorders such as Parkinson’s disease are effective but limited by undesirable and intractable side effects. Developing more effective therapies will require better understanding of what causes basal ganglia dys-regulation and why medication-induced side effects develop. Although basal ganglia have been extensively studied in the last decades, its circuit anatomy is very complex, and significant controversy exists as to how the interplay of different basal ganglia nuclei process motor information and output. We have recently identified the importance of an underappreciated collateral projection that bridges the striatal output direct pathway with the indirect pathway. These bridging collaterals are extremely plastic in the adult brain and are involved in the regulation of motor balance. Our findings add a new angle to the classical model of basal ganglia circuitry that could be exploited for the development of new therapies against movement disorders. In this Scientific Perspective, we describe the function of bridging collaterals and other recent discoveries that challenge the simplicity of the classical basal ganglia circuit model. We then discuss the potential implication of bridging collaterals in the pathophysiology of Parkinson’s disease and schizophrenia. Because dopamine D2 receptors and striatal neuron excitability have been found to regulate the density of bridging collaterals, we propose that targeting these projections downstream of D2 receptors could be a possible strategy for the treatment of basal ganglia disorders. PMID:26018615

  2. 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

  3. Saccade learning with concurrent cortical and subcortical basal ganglia loops

    PubMed Central

    N'Guyen, Steve; Thurat, Charles; Girard, Benoît

    2014-01-01

    The Basal Ganglia (BG) is a central structure involved in multiple cortical and subcortical loops. Some of these loops are believed to be responsible for saccade target selection. We study here how the very specific structural relationships of these saccadic loops can affect the ability of learning spatial and feature-based tasks. We propose a model of saccade generation with reinforcement learning capabilities based on our previous BG and superior colliculus models. It is structured around the interactions of two parallel cortico-basal loops and one tecto-basal loop. The two cortical loops separately deal with spatial and non-spatial information to select targets in a concurrent way. The subcortical loop is used to make the final target selection leading to the production of the saccade. These different loops may work in concert or disturb each other regarding reward maximization. Interactions between these loops and their learning capabilities are tested on different saccade tasks. The results show the ability of this model to correctly learn basic target selection based on different criteria (spatial or not). Moreover the model reproduces and explains training dependent express saccades toward targets based on a spatial criterion. Finally, the model predicts that in absence of prefrontal control, the spatial loop should dominate. PMID:24795615

  4. [Cortico-basal ganglia circuits--parallel closed loops and convergent/divergent connections].

    PubMed

    Miyachi, Shigehiro

    2009-04-01

    The basal ganglia play important roles not only in motor control but also in higher cognitive functions such as reinforcement learning and procedural memory. Anatomical studies on the neuronal connections between the basal ganglia, cerebral cortex, and thalamus have demonstrated that these nuclei and cortical areas are interconnected via independent parallel loop circuits. The association, motor, and limbic cortices project to specific domains in the striatum, which, in turn, project back to the corresponding cortical areas via the substantia nigra/globus pallidus and the thalamus. Likewise, subregions in the motor cortex representing different body parts project to specific regions in the putamen, which project back to the original motor cortical regions. These parallel loops have been thought to be the basic anatomical structures involved in the basal ganglia functions. Furthermore, neuronal projections communicating between different loops (or functional domains) have also been discovered. A considerable number of corticostriatal projections from functionally interrelated cortical areas (e. g., hand representations of the motor cortex and somatosensory cortex) converge at the striatum. It has also been suggested that the location of the substantia nigra is in such that it can transmit information from the 'limbic loop' to the 'association loop', and from the 'association loop' to the 'motor loop'. Furthermore, a recent transsynaptic neuronal tracing study conducted at our laboratory demonstrated that the ventral (limbic) striatum sends divergent outputs to multiple regions in the frontal cortex. These 'inter-loop' connections would be important for the integration of information to achieve goal-directed behaviors. PMID:19378804

  5. Queuing of concurrent movement plans by basal ganglia.

    PubMed

    Bhutani, Neha; Sureshbabu, Ramakrishnan; Farooqui, Ausaf A; Behari, Madhuri; Goyal, Vinay; Murthy, Aditya

    2013-06-12

    How the brain converts parallel representations of movement goals into sequential movements is not known. We tested the role of basal ganglia (BG) in the temporal control of movement sequences by a convergent approach involving inactivation of the BG by muscimol injections into the caudate nucleus of monkeys and assessing behavior of Parkinson's disease patients, performing a modified double-step saccade task. We tested a critical prediction of a class of competitive queuing models that explains serial behavior as the outcome of a selection of concurrently activated goals. In congruence with these models, we found that inactivation or impairment of the BG unmasked the parallel nature of goal representations such that a significantly greater extent of averaged saccades, curved saccades, and saccade sequence errors were observed. These results suggest that the BG perform a form of competitive queuing, holding the second movement plan in abeyance while the first movement is being executed, allowing the proper temporal control of movement sequences. PMID:23761894

  6. A dystonic syndrome associated with anti-basal ganglia antibodies.

    PubMed

    Edwards, M J; Dale, R C; Church, A J; Giovannoni, G; Bhatia, K P

    2004-06-01

    Anti-basal ganglia antibodies (ABGA) have been associated with movement disorders (usually tics and chorea) and psychiatric disturbance in children. This report describes five adult and adolescent patients (one male, four females; mean age of onset, 16 years (range, 13-35)) who presented subacutely with a clinical syndrome dominated by dystonia and had ABGA binding to antigens of similar molecular weights to those seen in Sydenham's chorea. Three patients had a clear history of respiratory infection before the onset of their symptoms. Three patients received immunosuppressive treatment, with three showing a notable reduction in symptoms. It is hypothesised that dystonia in adults or adolescents may be part of the clinical spectrum of the post-infectious syndrome associated with ABGA. PMID:15146015

  7. Intraparenchymal meningioma within the basal ganglia of a child: A case report.

    PubMed

    Reynolds, Matthew R; Boland, Michael R; Arias, Eric J; Farrell, Michael; Javadpour, Mohsen; Caird, John

    2016-06-01

    Intraparenchymal meningiomas are rare. To date, no such lesion has been reported within the basal ganglia of a paediatric patient. Here, we describe the case of a 15-year-old-boy who presented with symptoms referable to a cystic, calcified, left basal ganglia intraparenchymal meningioma and discuss the surgical management of this lesion. PMID:26466020

  8. Distinct Hippocampal and Basal Ganglia Contributions to Probabilistic Learning and Reversal

    ERIC Educational Resources Information Center

    Shohamy, Daphna; Myers, Catherine E.; Hopkins, Ramona O.; Sage, Jake; Gluck, Mark A.

    2009-01-01

    The hippocampus and the basal ganglia are thought to play fundamental and distinct roles in learning and memory, supporting two dissociable memory systems. Interestingly, however, the hippocampus and the basal ganglia have each, separately, been implicated as necessary for reversal learning--the ability to adaptively change a response when…

  9. Unilateral germinomas involving the basal ganglia and thalamus.

    PubMed

    Kobayashi, T; Kageyama, N; Kida, Y; Yoshida, J; Shibuya, N; Okamura, K

    1981-07-01

    Clinical characteristics of six cases of germinoma involving a unilateral basal ganglion and thalamus are summarized. The incidence was estimated as 10% of all intracranial germinomas. The average age at the onset was 10.5 years. The sex incidence showed a male dominance. The clinical course was slowly progressive, and the average duration between onset and diagnosis was 2 years 5 months. Common symptoms and signs were hemiparesis in all cases, fever of unknown origin and eye symptoms in most, mental deterioration and psychiatric signs in three, and convulsions, pubertas praecox, and diabetes insipidus in two. Signs of increased intracranial pressure were found in only two cases in the later state of the disease. Early diagnosis is difficult because of nonspecific symptomatology and slow progression. Carotid angiography and pneumoencephalography showed abnormal findings compatible with basal ganglia and thalamic tumors, but not specific to germinoma. Ipsilateral cortical atrophy and ventricular dilatation might be significant findings. Radioisotope scanning was useful. Computerized tomography scans were the best method of detecting the location and nature of this tumor, and repeat scans showed response to radiation therapy. PMID:7241216

  10. Shape of the basal ganglia in preadolescent children is associated with cognitive performance.

    PubMed

    Sandman, Curt A; Head, Kevin; Muftuler, L Tugan; Su, Lydia; Buss, Claudia; Davis, Elysia Poggi

    2014-10-01

    of function, and that distortion of the basal ganglia may be a neurophenotype for risk of developmental impairment. PMID:24844741

  11. SHAPE OF THE BASAL GANGLIA IN PREADOLESCENT CHILDREN IS ASSOCIATED WITH COGNITIVE PERFORMANCE

    PubMed Central

    Sandman, Curt A.; Head, Kevin; Muftuler, L. Tugan; Su, Lydia; Buss, Claudia; Davis, Elysia Poggi.

    2014-01-01

    measure of function, and that distortion of the basal ganglia may be a neurophenotype for risk of developmental impairment. PMID:24844741

  12. Modeling basal ganglia for understanding Parkinsonian reaching movements.

    PubMed

    Magdoom, K N; Subramanian, D; Chakravarthy, V S; Ravindran, B; Amari, Shun-Ichi; Meenakshisundaram, N

    2011-02-01

    We present a computational model that highlights the role of basal ganglia (BG) in generating simple reaching movements. The model is cast within the reinforcement learning (RL) framework with correspondence between RL components and neuroanatomy as follows: dopamine signal of substantia nigra pars compacta as the temporal difference error, striatum as the substrate for the critic, and the motor cortex as the actor. A key feature of this neurobiological interpretation is our hypothesis that the indirect pathway is the explorer. Chaotic activity, originating from the indirect pathway part of the model, drives the wandering, exploratory movements of the arm. Thus, the direct pathway subserves exploitation, while the indirect pathway subserves exploration. The motor cortex becomes more and more independent of the corrective influence of BG as training progresses. Reaching trajectories show diminishing variability with training. Reaching movements associated with Parkinson's disease (PD) are simulated by reducing dopamine and degrading the complexity of indirect pathway dynamics by switching it from chaotic to periodic behavior. Under the simulated PD conditions, the arm exhibits PD motor symptoms like tremor, bradykinesia and undershooting. The model echoes the notion that PD is a dynamical disease. PMID:21105828

  13. Origins of basal ganglia output signals in singing juvenile birds

    PubMed Central

    Pidoux, Morgane; Bollu, Tejapratap; Riccelli, Tori

    2014-01-01

    Across species, complex circuits inside the basal ganglia (BG) converge on pallidal output neurons that exhibit movement-locked firing patterns. Yet the origins of these firing patterns remain poorly understood. In songbirds during vocal babbling, BG output neurons homologous to those found in the primate internal pallidal segment are uniformly activated in the tens of milliseconds prior to syllable onsets. To test the origins of this remarkably homogenous BG output signal, we recorded from diverse upstream BG cell types during babbling. Prior to syllable onsets, at the same time that internal pallidal segment-like neurons were activated, putative medium spiny neurons, fast spiking and tonically active interneurons also exhibited transient rate increases. In contrast, pallidal neurons homologous to those found in primate external pallidal segment exhibited transient rate decreases. To test origins of these signals, we performed recordings following lesion of corticostriatal inputs from premotor nucleus HVC. HVC lesions largely abolished these syllable-locked signals. Altogether, these findings indicate a striking homogeneity of syllable timing signals in the songbird BG during babbling and are consistent with a role for the indirect and hyperdirect pathways in transforming cortical inputs into BG outputs during an exploratory behavior. PMID:25392171

  14. Origins of basal ganglia output signals in singing juvenile birds.

    PubMed

    Pidoux, Morgane; Bollu, Tejapratap; Riccelli, Tori; Goldberg, Jesse H

    2015-02-01

    Across species, complex circuits inside the basal ganglia (BG) converge on pallidal output neurons that exhibit movement-locked firing patterns. Yet the origins of these firing patterns remain poorly understood. In songbirds during vocal babbling, BG output neurons homologous to those found in the primate internal pallidal segment are uniformly activated in the tens of milliseconds prior to syllable onsets. To test the origins of this remarkably homogenous BG output signal, we recorded from diverse upstream BG cell types during babbling. Prior to syllable onsets, at the same time that internal pallidal segment-like neurons were activated, putative medium spiny neurons, fast spiking and tonically active interneurons also exhibited transient rate increases. In contrast, pallidal neurons homologous to those found in primate external pallidal segment exhibited transient rate decreases. To test origins of these signals, we performed recordings following lesion of corticostriatal inputs from premotor nucleus HVC. HVC lesions largely abolished these syllable-locked signals. Altogether, these findings indicate a striking homogeneity of syllable timing signals in the songbird BG during babbling and are consistent with a role for the indirect and hyperdirect pathways in transforming cortical inputs into BG outputs during an exploratory behavior. PMID:25392171

  15. Basal ganglia outputs map instantaneous position coordinates during behavior.

    PubMed

    Barter, Joseph W; Li, Suellen; Sukharnikova, Tatyana; Rossi, Mark A; Bartholomew, Ryan A; Yin, Henry H

    2015-02-11

    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

  16. 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

  17. Reversible Acute Parkinsonism and Bilateral Basal Ganglia Lesions in a Diabetic Uremic Patient

    PubMed Central

    Nzwalo, Hipólito; Sá, Francisca; Capela, Carlos; Ferreira, Fátima; Basílio, Carlos

    2012-01-01

    The syndrome of bilateral basal ganglia lesions in diabetic uremic patients is a rare disorder mostly reported in Asians. There are few reports of the syndrome in Caucasians. It manifests as an acute hyperkinetic or hypokinetic extrapyramidal disorder in association with uniform neuroimaging findings of bilateral symmetrical basal ganglia changes in diabetics undergoing hemodialysis. Its pathophysiology remains largely unknown. Thus, we report a typical case of the syndrome in a Caucasian patient who developed an acute and reversible akinetic rigid parkinsonism secondary to bilateral basal ganglia lesions. PMID:23185167

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

    PubMed

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

    2016-03-22

    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

  19. 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

  20. Competing basal ganglia pathways determine the difference between stopping and deciding not to go.

    PubMed

    Dunovan, Kyle; Lynch, Brighid; Molesworth, Tara; Verstynen, Timothy

    2015-01-01

    The architecture of corticobasal ganglia pathways allows for many routes to inhibit a planned action: the hyperdirect pathway performs fast action cancellation and the indirect pathway competitively constrains execution signals from the direct pathway. We present a novel model, principled off of basal ganglia circuitry, that differentiates control dynamics of reactive stopping from intrinsic no-go decisions. Using a nested diffusion model, we show how reactive braking depends on the state of an execution process. In contrast, no-go decisions are best captured by a failure of the execution process to reach the decision threshold due to increasing constraints on the drift rate. This model accounts for both behavioral and functional MRI (fMRI) responses during inhibitory control tasks better than alternative models. The advantage of this framework is that it allows for incorporating the effects of context in reactive and proactive control into a single unifying parameter, while distinguishing action cancellation from no-go decisions. PMID:26402462

  1. 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. PMID:25595501

  2. 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

    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 movement

  3. 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

  4. Quantitation of the human basal ganglia with Positron Emission Tomography

    SciTech Connect

    Bendriem, B.; Dewey, S.L.; Schlyer, D.J.; Wolf, A.P.; Volkow, N.D.

    1990-01-01

    The accurate measurement of the concentration of a radioisotope in small structures with PET requires a correction for quantitation loss due to the partial volume effect and the effect of scattered radiation. To evaluate errors associated with measures in the human basal ganglia (BG) we have built a unilateral model of the BG that we have inserted in a 20 cm cylinder. The recovery coefficient (RC = measured activity/true activity) for our BG phantom has been measured on a CTI tomograph (model 931-08/12) with different background concentrations (contrast) and at different axial locations in the gantry. The BG was visualized on 4 or 5 slices depending on its position in the gantry and on the contrast used. The RC was 0.75 with no background (contrast equal to 1.0). Increasing the relative radioactivity concentration in the background increased the RC from 0.75 to 2.00 when the contrast was {minus}0.7 (BG < Background). The RC was also affected by the size and the shape of the region of interest (ROI) used (RC from 0.75 to 0.67 with ROI size from 0.12 to 1.41 cm{sup 2}). These results show that accurate RC correction depends not only on the volume of the structure but also on its contrast with its surroundings as well as on the selection of the ROI. They also demonstrate that the higher the contrast the more sensitive to axial positioning PET measurements in the BG are. These data provide us with some information about the variability of PET measurements in small structure like the BG and we have proposed some strategies to improve the reproducibility. 18 refs., 3 figs., 5 tabs.

  5. Bilateral Traumatic Basal Ganglia Hemorrhage Associated With Epidural Hematoma: Case Report and Literature Review

    PubMed Central

    Calderon-Miranda, Willem Guillermo; Alvis-Miranda, Hernando Raphael; Alcala-Cerra, Gabriel; M. Rubiano, Andres; Moscote-Salazar, Luis Rafael

    2014-01-01

    Traumatic basal ganglia hematoma is a rare condition defined as presence of hemorrhagic lesions in basal ganglia or adjacent structures suchas internal capsule, putamen and thalamus. Bilateral basal ganglia hematoma are among the devastating and rare condition. We herein report a 28-year old man, a victim of car-car accident who was brought to our surgical emergency room by immediate loss of consciousness and was diagnosed to have hyperdense lesion in the basal ganglia bilaterally, with the presence of right parietal epidural hematoma. Craniotomy and epidural hematoma drainage were considered, associated to conservative management of gangliobasal traumatic contusions. On day 7 the patient had sudden neurologic deterioration, cardiac arrest unresponsive to resuscitation. Management of these lesions is similar to any other injury in moderate to severe traumatic injury. The use of intracranial pressure monitoring must be guaranteed. PMID:27162882

  6. Bilateral Traumatic Basal Ganglia Hemorrhage Associated With Epidural Hematoma: Case Report and Literature Review.

    PubMed

    Calderon-Miranda, Willem Guillermo; Alvis-Miranda, Hernando Raphael; Alcala-Cerra, Gabriel; M Rubiano, Andres; Moscote-Salazar, Luis Rafael

    2014-07-01

    Traumatic basal ganglia hematoma is a rare condition defined as presence of hemorrhagic lesions in basal ganglia or adjacent structures suchas internal capsule, putamen and thalamus. Bilateral basal ganglia hematoma are among the devastating and rare condition. We herein report a 28-year old man, a victim of car-car accident who was brought to our surgical emergency room by immediate loss of consciousness and was diagnosed to have hyperdense lesion in the basal ganglia bilaterally, with the presence of right parietal epidural hematoma. Craniotomy and epidural hematoma drainage were considered, associated to conservative management of gangliobasal traumatic contusions. On day 7 the patient had sudden neurologic deterioration, cardiac arrest unresponsive to resuscitation. Management of these lesions is similar to any other injury in moderate to severe traumatic injury. The use of intracranial pressure monitoring must be guaranteed. PMID:27162882

  7. Basal Ganglia Structures Differentially Contribute to Verbal Fluency: Evidence from Human Immunodeficiency Virus (HIV)-Infected Adults

    ERIC Educational Resources Information Center

    Thames, April D.; Foley, Jessica M.; Wright, Matthew J.; Panos, Stella E.; Ettenhofer, Mark; Ramezani, Amir; Streiff, Vanessa; El-Saden, Suzie; Goodwin, Scott; Bookheimer, Susan Y.; Hinkin, Charles H.

    2012-01-01

    Background: The basal ganglia (BG) are involved in executive language functions (i.e., verbal fluency) through their connections with cortical structures. The caudate and putamen receive separate inputs from prefrontal and premotor cortices, and may differentially contribute to verbal fluency performance. We examined BG integrity in relation to…

  8. Rhythmic Cortical Neurons Increase their Oscillations and Sculpt Basal Ganglia Signaling During Motor Learning

    PubMed Central

    Day, Nancy F.; Nick, Teresa A.

    2014-01-01

    The function and modulation of neural circuits underlying motor skill may involve rhythmic oscillations (Feller, 1999; Marder and Goaillard, 2006; Churchland et al., 2012). In the proposed pattern generator for birdsong, the cortical nucleus HVC, the frequency and power of oscillatory bursting during singing increases with development (Crandall et al., 2007; Day et al., 2009). We examined the maturation of cellular activity patterns that underlie these changes. Single unit ensemble recording combined with antidromic identification (Day et al., 2011) was used to study network development in anesthetized zebra finches. Autocovariance quantified oscillations within single units. A subset of neurons oscillated in the theta/alpha/mu/beta range (8–20 Hz), with greater power in adults compared to juveniles. Across the network, the normalized oscillatory power in the 8–20 Hz range was greater in adults than juveniles. In addition, the correlated activity between rhythmic neuron pairs increased with development. We next examined the functional impact of the oscillators on the output neurons of HVC. We found that the firing of oscillatory neurons negatively correlated with the activity of cortico-basal ganglia neurons (HVCXs), which project to Area X (the song basal ganglia). If groups of oscillators work together to tonically inhibit and precisely control the spike timing of adult HVCXs with coordinated release from inhibition, then the activity of HVCXs in juveniles should be decreased relative to adults due to uncorrelated, tonic inhibition. Consistent with this hypothesis, HVCXs had lower activity in juveniles. These data reveal network changes that shape cortical-to-basal ganglia signaling during motor learning. PMID:23776169

  9. Models of basal ganglia and cerebellum for sensorimotor integration and predictive control

    NASA Astrophysics Data System (ADS)

    Jabri, Marwan A.; Huang, Jerry; Coenen, Olivier J. D.; Sejnowski, Terrence J.

    2000-10-01

    This paper presents a sensorimotor architecture integrating computational models of a cerebellum and a basal ganglia and operating on a microrobot. The computational models enable a microrobot to learn to track a moving object and anticipate future positions using a CCD camera. The architecture features pre-processing modules for coordinate transformation and instantaneous orientation extraction. Learning of motor control is implemented using predictive Hebbian reinforcement-learning algorithm in the basal ganglia model. Learning of sensory predictions makes use of a combination of long-term depression (LTD) and long-term potentiation (LTP) adaptation rules within the cerebellum model. The basal ganglia model uses the visual inputs to develop sensorimotor mapping for motor control, while the cerebellum module uses robot orientation and world- coordinate transformed inputs to predict the location of the moving object in a robot centered coordinate system. We propose several hypotheses about the functional role of cell populations in the cerebellum and argue that mossy fiber projections to the deep cerebellar nucleus (DCN) could play a coordinate transformation role and act as gain fields. We propose that such transformation could be learnt early in the brain development stages and could be guided by the activity of the climbing fibers. Proprioceptor mossy fibers projecting to the DCN and providing robot orientation with respect to a reference system could be involved in this case. Other mossy fibers carrying visual sensory input provide visual patterns to the granule cells. The combined activities of the granule and the Purkinje cells store spatial representations of the target patterns. The combinations of mossy and Purkinje projections to the DCN provide a prediction of the location of the moving target taking into consideration the robot orientation. Results of lesion simulations based on our model show degradations similar to those reported in cerebellar lesion

  10. Automatic Evaluation of Speech Rhythm Instability and Acceleration in Dysarthrias Associated with Basal Ganglia Dysfunction.

    PubMed

    Rusz, Jan; Hlavnička, Jan; Čmejla, Roman; Růžička, Evžen

    2015-01-01

    Speech rhythm abnormalities are commonly present in patients with different neurodegenerative disorders. These alterations are hypothesized to be a consequence of disruption to the basal ganglia circuitry involving dysfunction of motor planning, programing, and execution, which can be detected by a syllable repetition paradigm. Therefore, the aim of the present study was to design a robust signal processing technique that allows the automatic detection of spectrally distinctive nuclei of syllable vocalizations and to determine speech features that represent rhythm instability (RI) and rhythm acceleration (RA). A further aim was to elucidate specific patterns of dysrhythmia across various neurodegenerative disorders that share disruption of basal ganglia function. Speech samples based on repetition of the syllable /pa/ at a self-determined steady pace were acquired from 109 subjects, including 22 with Parkinson's disease (PD), 11 progressive supranuclear palsy (PSP), 9 multiple system atrophy (MSA), 24 ephedrone-induced parkinsonism (EP), 20 Huntington's disease (HD), and 23 healthy controls. Subsequently, an algorithm for the automatic detection of syllables as well as features representing RI and RA were designed. The proposed detection algorithm was able to correctly identify syllables and remove erroneous detections due to excessive inspiration and non-speech sounds with a very high accuracy of 99.6%. Instability of vocal pace performance was observed in PSP, MSA, EP, and HD groups. Significantly increased pace acceleration was observed only in the PD group. Although not significant, a tendency for pace acceleration was observed also in the PSP and MSA groups. Our findings underline the crucial role of the basal ganglia in the execution and maintenance of automatic speech motor sequences. We envisage the current approach to become the first step toward the development of acoustic technologies allowing automated assessment of rhythm in dysarthrias. PMID:26258122

  11. [THE ORGANIZATION OF PROJECTIONS OF MIDBRAIN LATERAL TEGMENTAL NUCLEI THE TO BRAIN BASAL GANGLIA IN DOGS].

    PubMed

    Gorbachevskaya, A I

    2015-01-01

    The organization of the projections of midbrain lateral tegmental nuclei (peripeduncular nucleus, paralemniscal nucleus, nucleus of the brachium of inferior colliculus) to functionally diverse nuclei of the basal ganglia system was studied in dogs (n = 34) by the method of retrograde axonal transport of horse-radish peroxidase. It was found that the midbrain nuclei studied were involved in functionally different circuits, containing the basal ganglia as their components. These nuclei innervate the regions of the putamen, globus pallidus, cuneate nucleus, subcuneate nucleus, which are the motor or the limbic structures on the basis of their predominant connections with the motor or the limbic brain nuclei, and also regions of the caudate nucleus, nucleus accumbens, entopeduncular nucleus, compact part of the pedunculopontine nucleus, which receive the projections from the functionally various structures. The analysis of Nissl-stained frontal sections allowed to refine the anatomical topography of the individual nuclei of the midbrain lateral tegmentum. The cholinergic nature of their neurons was demonstrated based on of the positive histochemical reaction to NADPH diaphorase. PMID:27141581

  12. The Role of Inhibition in Generating and Controlling Parkinson’s Disease Oscillations in the Basal Ganglia

    PubMed Central

    Kumar, Arvind; Cardanobile, Stefano; Rotter, Stefan; Aertsen, Ad

    2011-01-01

    Movement disorders in Parkinson’s disease (PD) are commonly associated with slow oscillations and increased synchrony of neuronal activity in the basal ganglia. The neural mechanisms underlying this dynamic network dysfunction, however, are only poorly understood. Here, we show that the strength of inhibitory inputs from striatum to globus pallidus external (GPe) is a key parameter controlling oscillations in the basal ganglia. Specifically, the increase in striatal activity observed in PD is sufficient to unleash the oscillations in the basal ganglia. This finding allows us to propose a unified explanation for different phenomena: absence of oscillation in the healthy state of the basal ganglia, oscillations in dopamine-depleted state and quenching of oscillations under deep-brain-stimulation (DBS). These novel insights help us to better understand and optimize the function of DBS protocols. Furthermore, studying the model behavior under transient increase of activity of the striatal neurons projecting to the indirect pathway, we are able to account for both motor impairment in PD patients and for reduced response inhibition in DBS implanted patients. PMID:22028684

  13. How preparation changes the need for top-down control of the basal ganglia when inhibiting premature actions.

    PubMed

    Jahfari, Sara; Verbruggen, Frederick; Frank, Michael J; Waldorp, Lourens J; Colzato, Lorenza; Ridderinkhof, K Richard; Forstmann, Birte U

    2012-08-01

    Goal-oriented signals from the prefrontal cortex gate the selection of appropriate actions in the basal ganglia. Key nodes within this fronto-basal ganglia action regulation network are increasingly engaged when one anticipates the need to inhibit and override planned actions. Here, we ask how the advance preparation of action plans modulates the need for fronto-subcortical control when a planned action needs to be withdrawn. Functional magnetic resonance imaging data were collected while human participants performed a stop task with cues indicating the likelihood of a stop signal being sounded. Mathematical modeling of go trial responses suggested that participants attained a more cautious response strategy when the probability of a stop signal increased. Effective connectivity analysis indicated that, even in the absence of stop signals, the proactive engagement of the full control network is tailored to the likelihood of stop trial occurrence. Importantly, during actual stop trials, the strength of fronto-subcortical projections was stronger when stopping had to be engaged reactively compared with when it was proactively prepared in advance. These findings suggest that fronto-basal ganglia control is strongest in an unpredictable environment, where the prefrontal cortex plays an important role in the optimization of reactive control. Importantly, these results further indicate that the advance preparation of action plans reduces the need for reactive fronto-basal ganglia communication to gate voluntary actions. PMID:22875921

  14. Cardiorespiratory fitness and its association with thalamic, hippocampal, and basal ganglia volumes in multiple sclerosis

    PubMed Central

    Motl, Robert W.; Pilutti, Lara A.; Hubbard, Elizabeth A.; Wetter, Nathan C.; Sosnoff, Jacob J.; Sutton, Bradley P.

    2015-01-01

    Background There is little known about cardiorespiratory fitness and its association with volumes of the thalamus, hippocampus, and basal ganglia in multiple sclerosis (MS). Such inquiry is important for identifying a possible behavioral approach (e.g., aerobic exercise training) that might change volumes of deep gray matter (DGM) structures associated with cognitive and motor functions in MS. Purpose This study examined the association between cardiorespiratory fitness and volumes of the thalamus, hippocampus, and basal ganglia in MS. Method We enrolled 35 persons with MS who underwent a maximal exercise test for measuring cardiorespiratory fitness as peak oxygen consumption (VO2peak) and brain MRI. Volumes of the thalamus, hippocampus, caudate, putamen, and pallidum were calculated from 3D T1-weighted structural brain images. We examined associations using partial (pr) correlations controlling for demographic and clinical variables. Results VO2peak was significantly associated with composite scaled volumes of the caudate(pr = .47, p < .01), putamen (pr = .44, p < .05), pallidum (pr = .40, p < .05), and hippocampus (pr = .42, p < .05), but not thalamus (pr = .31, p = .09), when controlling for sex, age, disability, and duration of MS. Conclusion Our results provide novel evidence that cardiorespiratory fitness is associated with volumes of DGM structures that are involved in motor and cognitive functions in MS. PMID:25844320

  15. Learning processing in the basal ganglia: a mosaic of broken mirrors.

    PubMed

    Da Cunha, Claudio; Wietzikoski, Evellyn Claudia; Dombrowski, Patrícia; Bortolanza, Mariza; Santos, Lucélia Mendes; Boschen, Suelen Lucio; Miyoshi, Edmar

    2009-04-12

    In the present review we propose a model to explain the role of the basal ganglia in sensorimotor and cognitive functions based on a growing body of behavioural, anatomical, physiological, and neurochemical evidence accumulated over the last decades. This model proposes that the body and its surrounding environment are represented in the striatum in a fragmented and repeated way, like a mosaic consisting of the fragmented images of broken mirrors. Each fragment forms a functional unit representing articulated parts of the body with motion properties, objects of the environment which the subject can approach or manipulate, and locations the subject can move to. These units integrate the sensory properties and movements related to them. The repeated and widespread distribution of such units amplifies the combinatorial power of the associations among them. These associations depend on the phasic release of dopamine in the striatum triggered by the saliency of stimuli and will be reinforced by the rewarding consequences of the actions related to them. Dopamine permits synaptic plasticity in the corticostriatal synapses. The striatal units encoding the same stimulus/action send convergent projections to the internal segment of the globus pallidus (GPi) and to the substantia nigra pars reticulata (SNr) that stimulate or hold the action through a thalamus-frontal cortex pathway. According to this model, this is how the basal ganglia select actions based on environmental stimuli and store adaptive associations as nondeclarative memories such as motor skills, habits, and memories formed by Pavlovian and instrumental conditioning. PMID:18977393

  16. Expression of muscarinic acetylcholine and dopamine receptor mRNAs in rat basal ganglia

    SciTech Connect

    Weiner, D.M. Howard Hughes Medical Inst., Bethesda, MD ); Levey, A.I. Johns Hopkins Univ., Baltimore, MD ); Brann, M.R. )

    1990-09-01

    Within the basal ganglia, acetylcholine and dopamine play a central role in the extrapyramidal control of motor function. The physiologic effects of these neurotransmitters are mediated by a diversity of receptor subtypes, several of which have now been cloned. Muscarinic acetylcholine receptors are encoded by five genes (m1-m5), and of the two known dopamine receptor subtypes (D1 and D2) the D2 receptor gene has been characterized. To gain insight into the physiological roles of each of these receptor subtypes, the authors prepared oligodeoxynucleotide probes to localize receptor subtype mRNAs within the rat striatum and substantia nigra by in situ hybridization histochemistry. Within the striatum, three muscarinic (m1, m2, m4) receptor mRNAs and the D2 receptor mRNA were detected. The m1 mRNA was expressed in most neurons; the m2 mRNA, in neurons which were both very large and rare; and the m4 and D2 mRNAs, in 40-50% of the neurons, one-third of which express both mRNAs. Within the substantia nigra, pars compacta, only the m5 and D2 mRNAs were detected, and most neurons expressed both mRNAs. These data provide anatomical evidence for the identity of the receptor subtypes which mediate the diverse effects of muscarinic and dopaminergic drugs on basal ganglia function.

  17. The role of the basal ganglia and cerebellum in language processing

    PubMed Central

    Booth, James R.; Wood, Lydia; Lu, Dong; Houk, James C.; Bitan, Tali

    2007-01-01

    The roles of the cerebellum and basal ganglia have typically been confined in the literature to motor planning and control. However, mounting evidence suggests that these structures are involved in more cognitive domains such as language processing. In the current study, we looked at effective connectivity (the influence that one brain region has on another) of the cerebellum and basal ganglia with regions thought to be involved in phonological processing, i.e. left inferior frontal gyrus and left lateral temporal cortex. We analyzed functional magnetic resonance imaging data (fMRI) obtained during a rhyming judgment task in adults using dynamic causal modeling (DCM). The results showed that the cerebellum has reciprocal connections with both left inferior frontal gyrus and left lateral temporal cortex, whereas the putamen has unidirectional connections into these two brain regions. Furthermore, the connections between cerebellum and these phonological processing areas were stronger than the connections between putamen and these areas. This pattern of results suggests that the putamen and cerebellum may have distinct roles in language processing. Based on research in the motor planning and control literature, we argue that the putamen engages in cortical initiation while the cerebellum amplifies and refines this signal to facilitate correct decision making. PMID:17189619

  18. Role of movement in long-term basal ganglia changes: implications for abnormal motor responses

    PubMed Central

    Simola, Nicola; Morelli, Micaela; Frazzitta, Giuseppe; Frau, Lucia

    2013-01-01

    Abnormal involuntary movements (AIMs) and dyskinesias elicited by drugs that stimulate dopamine receptors in the basal ganglia are a major issue in the management of Parkinson’s disease (PD). Preclinical studies in dopamine-denervated animals have contributed to the modeling of these abnormal movements, but the precise neurochemical and functional mechanisms underlying these untoward effects are still elusive. It has recently been suggested that the performance of movement may itself promote the later emergence of drug-induced motor complications, by favoring the generation of aberrant motor memories in the dopamine-denervated basal ganglia. Our recent results from hemiparkinsonian rats subjected to the priming model of dopaminergic stimulation are in agreement with this. These results demonstrate that early performance of movement is crucial for the manifestation of sensitized rotational behavior, indicative of an abnormal motor response, and neurochemical modifications in selected striatal neurons following a dopaminergic challenge. Building on this evidence, this paper discusses the possible role of movement performance in drug-induced motor complications, with a look at the implications for PD management. PMID:24167489

  19. Increase of glucose consumption in basal ganglia, thalamus and frontal cortex of patients with spasmodic torticollis

    SciTech Connect

    Grassi, F.; Bressi, S.; Antoni, M.

    1994-05-01

    The pathophysiology of spasmodic torticollis, a focal dystonia involving neck muscles, is still unclear. Positron emission tomography (PET) studies showed either an increase as well as a decrease of regional cerebral metabolic rate of glucose (rCMRglu) in basal ganglia. In the present study, [18F]FDG and PET was used to measure rCMRglu in 10 patients with spasmodic torticollis (mean age 50.37 {plus_minus} 11.47) and 10 age matched controls. All cases with a short disease duration, were untreated. A factorial analysis of variance revealed a significant bilateral increase of glucose consumption in caudate nucleus and pallidum/putamen complex (p>0.004) and in the cerebellum (p>0.001). The rCMRglu increase in the motor/premotor cortex and in the thalamus reached a trend towards significance (p<0.05). These preliminary data show enhanced metabolism in basal ganglia and cerebellum as the functional correlate of focal dystonia. A recently proposed model suggests that dystonia would be the consequence of a putaminal hyperactivity, leading to the breakdown of the pallidal inhibitory control on thalamus and thalamo-cortical projections.

  20. 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

  1. Bilateral basal ganglia calcification and recurrent generalized seizures as initial presentation of idiopathic hypoparathyroidism in an infant

    PubMed Central

    Bhat, Manzoor Ahmad; Laway, Bashir Ahmad; Mustafa, Farhat

    2015-01-01

    Pathological calcification of basal ganglia has been encountered in children since long back and is associated with various disease entities both acute and chronic. Idiopathic hypoparathyroidism is an important cause of basal ganglia calcification and can account for up to 73.8% of cases. The pathogenesis of basal ganglia calcification in hypoparathyroidism is not clear, however, a high calcium-phosphorus product and poor calcium control are believed to be directly related to calcification. Besides, a direct correlation is seen with the duration of hypocalcemia; the critical duration being ≥4 years. In the presented patient, basal ganglia calcification was seen at a very young age of 6 months. To best of our knowledge, this is probably the youngest case of bilateral basal ganglia calcification in idiopathic hypoparathyroidism in literature. This suggests that besides duration of hypocalcemia, certain genetic factors and the intrauterine milieu may have a role in the pathogenesis of basal ganglia calcification. PMID:26167230

  2. Diffusion Tensor Imaging of Basal Ganglia and Thalamus in Amyotrophic Lateral Sclerosis

    PubMed Central

    Sharma, Khema R.; Sheriff, Sulaiman; Maudsley, Andrew; Govind, Varan

    2016-01-01

    Purpose To assess the involvement of basal ganglia and thalamus in patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI) method. Methods Fourteen definite-ALS patients and 12 age-matched controls underwent whole brain DTI on a 3T scanner. Mean-diffusivity (MD) and fractional anisotropy (FA) were obtained bilaterally from the basal ganglia and thalamus in the regions-of-interest (ROI). Results The MD was significantly higher (p < 0.02) in basal ganglia and thalamus in patients with ALS compared with controls. Correspondingly, the FA was significantly lower (p < 0.02) in these structures, except in caudate (p =0.04) and putamen (p = 0.06) in patients compared with controls. There were mild to strong correlations (r: 0.3 – 0.7) between the DTI measures of basal ganglia and finger–tap, foot-tap, and lip-and-tongue-movement-rate. Conclusions The increased MD in basal ganglia and thalamus, and decreased FA in globus pallidus and thalamus are indicative of neuronal loss or dysfunction in these structures. PMID:22273090

  3. 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. PMID:22885186

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

    PubMed

    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

    2015-05-01

    The basal ganglia are phylogenetically conserved subcortical nuclei necessary for coordinated motor action and reward learning. Current models postulate that the basal ganglia modulate cerebral cortex indirectly via an inhibitory output to thalamus, bidirectionally controlled by direct- and indirect-pathway striatal projection neurons (dSPNs and iSPNs, respectively). The basal ganglia thalamic output sculpts cortical activity by interacting with signals from sensory and motor systems. Here we describe a direct projection from the globus pallidus externus (GP), a central nucleus of the basal ganglia, 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, 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 signalling, revealing a pathway by which drugs that target dopamine receptors for the treatment of neuropsychiatric disorders can act in the basal ganglia to modulate frontal cortices. PMID:25739505

  5. The place of dopamine in the cortico-basal ganglia circuit.

    PubMed

    Haber, S N

    2014-12-12

    The midbrain dopamine (DA) neurons play a central role in developing appropriate goal-directed behaviors, including the motivation and cognition to develop appropriate actions to obtain a specific outcome. Indeed, subpopulations of DA neurons have been associated with these different functions: the mesolimbic, mesocortical, and nigrostriatal pathways. The mesolimbic and nigrostriatal pathways are an integral part of the basal ganglia through its reciprocal connections to the ventral and dorsal striatum respectively. This chapter reviews the connections of the midbrain DA cells and their role in integrating information across limbic, cognitive and motor functions. Emphasis is placed on the interface between these functional domains within the striatum through corticostriatal connections, through the striato-nigro-striatal connection, and through the lateral habenula projection to the midbrain. PMID:25445194

  6. Distinct Neurogenomic States in Basal Ganglia Subregions Relate Differently to Singing Behavior in Songbirds

    PubMed Central

    Hilliard, Austin T.; Miller, Julie E.; Horvath, Steve; White, Stephanie A.

    2012-01-01

    Both avian and mammalian basal ganglia are involved in voluntary motor control. In birds, such movements include hopping, perching and flying. Two organizational features that distinguish the songbird basal ganglia are that striatal and pallidal neurons are intermingled, and that neurons dedicated to vocal-motor function are clustered together in a dense cell group known as area X that sits within the surrounding striato-pallidum. This specification allowed us to perform molecular profiling of two striato-pallidal subregions, comparing transcriptional patterns in tissue dedicated to vocal-motor function (area X) to those in tissue that contains similar cell types but supports non-vocal behaviors: the striato-pallidum ventral to area X (VSP), our focus here. Since any behavior is likely underpinned by the coordinated actions of many molecules, we constructed gene co-expression networks from microarray data to study large-scale transcriptional patterns in both subregions. Our goal was to investigate any relationship between VSP network structure and singing and identify gene co-expression groups, or modules, found in the VSP but not area X. We observed mild, but surprising, relationships between VSP modules and song spectral features, and found a group of four VSP modules that were highly specific to the region. These modules were unrelated to singing, but were composed of genes involved in many of the same biological processes as those we previously observed in area X-specific singing-related modules. The VSP-specific modules were also enriched for processes disrupted in Parkinson's and Huntington's Diseases. Our results suggest that the activation/inhibition of a single pathway is not sufficient to functionally specify area X versus the VSP and support the notion that molecular processes are not in and of themselves specialized for behavior. Instead, unique interactions between molecular pathways create functional specificity in particular brain regions during

  7. Evolutionary and developmental contributions for understanding the organization of the basal ganglia.

    PubMed

    Medina, Loreta; Abellán, Antonio; Vicario, Alba; Desfilis, Ester

    2014-01-01

    Herein we take advantage of the evolutionary developmental biology approach in order to improve our understanding of both the functional organization and the evolution of the basal ganglia, with a particular focus on the globus pallidus. Therefore, we review data on the expression of developmental regulatory genes (that play key roles in patterning, regional specification and/or morphogenesis), gene function and fate mapping available in different vertebrate species, which are useful to (a) understand the embryonic origin and basic features of each neuron subtype of the basal ganglia (including neurotransmitter/neuropeptide expression and connectivity patterns); (b) identify the same (homologous) subpopulations in different species and the degree of variation or conservation throughout phylogeny, and (c) identify possible mechanisms that may explain the evolution of the basal ganglia. These data show that the globus pallidus of rodents contains two major subpopulations of GABAergic projection neurons: (1) neurons containing parvalbumin and neurotensin-related hexapetide (LANT6), with descending projections to the subthalamus and substantia nigra, which originate from progenitors expressing Nkx2.1, primarily located in the pallidal embryonic domain (medial ganglionic eminence), and (2) neurons containing preproenkephalin (and possibly calbindin), with ascending projections to the striatum, which appear to originate from progenitors expressing Islet1 in the striatal embryonic domain (lateral ganglionic eminence). Based on data on Nkx2.1, Islet1, LANT6 and proenkephalin, it appears that both cell types are also present in the globus pallidus/dorsal pallidum of chicken, frog and lungfish. In chicken, the globus pallidus also contains neurons expressing substance P (SP), perhaps originating in the striatal embryonic domain. In ray-finned and cartilaginous fishes, the pallidum contains at least the Nkx2.1 lineage cell population (likely representing the neurons

  8. Immunohistochemical study on the distribution of canonical transient receptor potential channels in rat basal ganglia.

    PubMed

    Chung, Yoon Hee; Kim, Daejin; Moon, Nam Joo; Oh, Chang Seok; Lee, Eunju; Shin, Dong Hoon; Kim, Sung Su; Lee, Won Bok; Lee, Jun-Young; Cha, Choong Ik

    2007-07-01

    In the present study, we examined the localizations of canonical transient receptor potential channels (TRPCs) in rat basal ganglia. The dot-like staining pattern of TRPC5 was observed through the globus pallidus (GP) and caudate-putamen. TRPC7 had a strikingly high level of expression in the neuropil in the GP. In the subthalamic nucleus, strong staining for TRPC5 was observed in the cell bodies, while moderate to high immunoreactivies for TRPC1, TRPC3, TRPC4 and TRPC7 were found in the cell bodies and surrounding neuropil. In the substantia nigra, immunoreactivities for TRPC3 and TRPC7 were prominent in the cell bodies and several processes in the pars compacta and pars reticulata. TRPC6 was expressed in the neuropil, not in the cell bodies. This study may provide useful data for the future investigations on the structural and functional properties of TRPCs. PMID:17590510

  9. 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

  10. Impaired Frontal-Basal Ganglia Connectivity in Male Adolescents with Conduct Disorder

    PubMed Central

    Gao, Junling; Shi, Huqing; Wang, Xiang; Jiang, Yali; Ming, Qingsen; Gao, Yidian; Ma, Ren; Yao, Shuqiao

    2015-01-01

    Alack of inhibition control has been found in subjects with conduct disorder (CD), but the underlying neuropathophysiology remains poorly understood. The current study investigated the different mechanism of inhibition control in adolescent-onset CD males (n = 29) and well-matched healthy controls (HCs) (n = 40) when performing a GoStop task by functional magnetic resonance images. Effective connectivity (EC) within the inhibition control network was analyzed using a stochastic dynamic causality model. We found that EC within the inhibition control network was significantly different in the CD group when compared to the HCs. Exploratory relationship analysis revealed significant negative associations between EC between the IFG and striatum and behavioral scale scores in the CD group. These results suggest for the first time that the failure of inhibition control in subjects with CD might be associated with aberrant connectivity of the frontal–basal ganglia pathways, especially between the IFG and striatum. PMID:26658732

  11. Task-rest modulation of basal ganglia connectivity in mild to moderate Parkinson's disease.

    PubMed

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

    2015-09-01

    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

  12. Basal ganglia lesions and the theory of fronto-subcortical loops: neuropsychological findings in two patients with left caudate lesions.

    PubMed

    Benke, Thomas; Delazer, Margarete; Bartha, Lisa; Auer, Alexandra

    2003-01-01

    Basal ganglia lesions have a high prevalence for associated behavioural impairments. However, the exact pattern of cognitive impairments and its relationship to individual basal ganglia lesion have rarely been investigated by means of a detailed neuropsychological and lesion study. Furthermore, different mechanisms have been proposed as relevant for the observed cognitive deficits; among these, the hypothesis of fronto-subcortical loops (Alexander et al., 1986) has made predictions regarding the relationship between the damage of particular striato-frontal circuits and the resulting behavioural impairment which await clinical confirmation. We present a study of two subjects who suffered a MRI-documented focal left basal ganglia hematoma. The two patients differed in their lesions; in one patient (PJ) large parts of the caudate nucleus were destroyed whereas in the other (AS) mainly the pallidum and putamen were lesioned and the caudate suffered only minor damage. In the acute phase, the behavioural and neuropsychological abnormalities were similar in both cases and included mainly abulia, an impairment of executive and attentional functions, and a severe amnestic syndrome. After several months many functions were restored in AS, whereas PJ's abilities remained largely defective. Based on these data and on previous case studies several conclusions are drawn. Left caudate lesions induce marked and long-lasting behavioural and neuropsychological impairments comprising predominantly drive, executive control, attention, and memory. The extent of lesion in the head of the caudate nucleus is the critical factor regarding the severity and the outcome of the syndrome, whereas damage to the putamen and pallidum is less crucial for cognitive functions. A subset of behavioural alterations, among them abulia, attentional and frontal-executive dysfunctions, can well be attributed to lesions of the anterior cingulate circuit and the dorsolateral-frontal circuit at the basal

  13. Competing basal ganglia pathways determine the difference between stopping and deciding not to go

    PubMed Central

    Dunovan, Kyle; Lynch, Brighid; Molesworth, Tara; Verstynen, Timothy

    2015-01-01

    The architecture of corticobasal ganglia pathways allows for many routes to inhibit a planned action: the hyperdirect pathway performs fast action cancellation and the indirect pathway competitively constrains execution signals from the direct pathway. We present a novel model, principled off of basal ganglia circuitry, that differentiates control dynamics of reactive stopping from intrinsic no-go decisions. Using a nested diffusion model, we show how reactive braking depends on the state of an execution process. In contrast, no-go decisions are best captured by a failure of the execution process to reach the decision threshold due to increasing constraints on the drift rate. This model accounts for both behavioral and functional MRI (fMRI) responses during inhibitory control tasks better than alternative models. The advantage of this framework is that it allows for incorporating the effects of context in reactive and proactive control into a single unifying parameter, while distinguishing action cancellation from no-go decisions. DOI: http://dx.doi.org/10.7554/eLife.08723.001 PMID:26402462

  14. Coupling in the cortico-basal ganglia circuit is aberrant in the ketamine model of schizophrenia.

    PubMed

    Cordon, Ivan; Nicolás, María Jesús; Arrieta, Sandra; Lopetegui, Eneko; López-Azcárate, Jon; Alegre, Manuel; Artieda, Julio; Valencia, Miguel

    2015-08-01

    Recent studies have suggested the implication of the basal ganglia in the pathogenesis of schizophrenia. To investigate this hypothesis, here we have used the ketamine model of schizophrenia to determine the oscillatory abnormalities induced in the rat motor circuit of the basal ganglia. The activity of free moving rats was recorded in different structures of the cortico-basal ganglia circuit before and after an injection of a subanesthesic dose of ketamine (10mg/kg). Spectral estimates of the oscillatory activity, phase-amplitude cross-frequency coupling interactions (CFC) and imaginary event-related coherence together with animals׳ behavior were analyzed. Oscillatory patterns in the cortico-basal ganglia circuit were highly altered by the effect of ketamine. CFC between the phases of low-frequency activities (delta, 1-4; theta 4-8Hz) and the amplitude of high-gamma (~80Hz) and high-frequency oscillations (HFO) (~150Hz) increased dramatically and correlated with the movement increment shown by the animals. Between-structure analyses revealed that ketamine had also a massive effect in the low-frequency mediated synchronization of the HFO's across the whole circuit. Our findings suggest that ketamine administration results in an aberrant hypersynchronization of the whole cortico-basal circuit where the tandem theta/HFO seems to act as the main actor in the hyperlocomotion shown by the animals. Here we stress the importance of the basal ganglia circuitry in the ketamine model of schizophrenia and leave the door open to further investigations devoted to elucidate to what extent these abnormalities also reflect the prominent neurophysiological deficits observed in schizophrenic patients. PMID:25910422

  15. Mirror-writing and reversed repetition of digits in a right-handed patient with left basal ganglia haematoma.

    PubMed Central

    Chia, L G; Kinsbourne, M

    1987-01-01

    A 57 year old right-handed Chinese man sustained a left basal ganglia haemorrhage resulting in speech disorder and right hemiplegia. He mirror-wrote with his left hand and during speech recovery repeated digits in reverse sequence. The abnormal right to left directionality possibly reflected release of right basal ganglia from left-sided control. Images PMID:3612156

  16. Association Between Invisible Basal Ganglia and ZNF335 Mutations: A Case Report.

    PubMed

    Sato, Rieko; Takanashi, Jun-Ichi; Tsuyusaki, Yu; Kato, Mitsuhiro; Saitsu, Hirotomo; Matsumoto, Naomichi; Takahashi, Takao

    2016-09-01

    ZNF335 was first reported in 2012 as a causative gene for microcephaly. Because only 1 consanguineous pedigree has ever been reported, the key clinical features associated with ZNF335 mutations remain unknown. In this article, we describe another family harboring ZNF335 mutations. The female proband was the first child of nonconsanguineous Japanese parents. At birth, microcephaly was absent; her head circumference was 32.0 cm (-0.6 SD). At 3 months, microcephaly was noted, (head circumference, 34.0 cm [-4.6 SD]). Brain MRI showed invisible basal ganglia, cerebral atrophy, brainstem hypoplasia, and cerebellar atrophy. At 33 months, (head circumference, 41.0 cm [-5.1 SD]), she had severe psychomotor retardation. After obtaining informed consent from her parents, we performed exome sequencing in the proband and identified 1 novel and 1 known mutation in ZNF335, namely, c.1399T>C (p.C467R) and c.1505A>G (p.Y502C), respectively. The mutations were individually transmitted by her parents, indicating that the proband was compound heterozygous for the mutations. Her brain imaging findings, including invisible basal ganglia, were similar to those observed in the previous case with ZNF335 mutations. We speculate that invisible basal ganglia may be the key feature of ZNF335 mutations. For infants presenting with both microcephaly and invisible basal ganglia, ZNF335 mutations should be considered as a differential diagnosis. PMID:27540107

  17. Stuttering and the Basal Ganglia Circuits: A Critical Review of Possible Relations

    ERIC Educational Resources Information Center

    Alm, Per A.

    2004-01-01

    The possible relation between stuttering and the basal ganglia is discussed. Important clues to the pathophysiology of stuttering are given by conditions known to alleviate dysfluency, like the rhythm effect, chorus speech, and singing. Information regarding pharmacologic trials, lesion studies, brain imaging, genetics, and developmental changes…

  18. 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…

  19. 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…

  20. 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

  1. 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…

  2. 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…

  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. A biologically constrained model of the whole basal ganglia addressing the paradoxes of connections and selection.

    PubMed

    Liénard, Jean; Girard, Benoît

    2014-06-01

    The basal ganglia nuclei form a complex network of nuclei often assumed to perform selection, yet their individual roles and how they influence each other is still largely unclear. In particular, the ties between the external and internal parts of the globus pallidus are paradoxical, as anatomical data suggest a potent inhibitory projection between them while electrophysiological recordings indicate that they have similar activities. Here we introduce a theoretical study that reconciles both views on the intra-pallidal projection, by providing a plausible characterization of the relationship between the external and internal globus pallidus. Specifically, we developed a mean-field model of the whole basal ganglia, whose parameterization is optimized to respect best a collection of numerous anatomical and electrophysiological data. We first obtained models respecting all our constraints, hence anatomical and electrophysiological data on the intrapallidal projection are globally consistent. This model furthermore predicts that both aforementioned views about the intra-pallidal projection may be reconciled when this projection is weakly inhibitory, thus making it possible to support similar neural activity in both nuclei and for the entire basal ganglia to select between actions. Second, we predicts that afferent projections are substantially unbalanced towards the external segment, as it receives the strongest excitation from STN and the weakest inhibition from the striatum. Finally, our study strongly suggests that the intrapallidal connection pattern is not focused but diffuse, as this latter pattern is more efficient for the overall selection performed in the basal ganglia. PMID:24077957

  5. Evidence for a glutamatergic projection from the zona incerta to the basal ganglia of rats.

    PubMed

    Heise, Claire E; Mitrofanis, John

    2004-01-19

    This study explores the organisation and neurochemical nature of the projections from the zona incerta (ZI) to the basal ganglia. Sprague-Dawley rats were anaesthetised with ketamine (100 mg/kg) and Rompun (10 mg/kg), and injections of cholera toxin subunit B were made into each of the following nuclei: the ZI, the substantia nigra (SN), the pedunculopontine tegmental nucleus (PpT), and the entopeduncular nucleus (Ep). Brains were aldehyde fixed, sectioned, and processed using standard methods. Tracer-labelled sections were then doubly labelled with antibodies to glutamate (Glu), nitric oxide synthase (NOS), parvalbumin (Pv), or glutamic acid decarboxylase (GAD; the latter two are markers for GABAergic cells); these neurochemicals characterise most types of ZI cells. After ZI injections, labelling was nonuniform across the different basal ganglia nuclei. The bulk of labelling, both anterograde and retrograde, was seen in the SN and PpT and, to a lesser extent, within the other nuclei of the basal ganglia (e.g., caudate-putamen, globus pallidus, subthalamus, Ep). In the SN, labelling was found in both major parts of the nucleus, the pars compacta and pars reticulata. Within the PpT, however, the bulk of labelling was limited to only one of the two sectors of the nucleus, namely, the pars dissipata (PpTd). The pars compacta of the PpT (PpTc) remained largely free of labelled profiles. After CTb injections into three basal ganglia nuclei (SN, PpT, Ep), most labelled cells in the ZI were glutamate+ and very few were NOS+ or gamma-aminobutyric acidergic. Overall, the results indicate that the ZI is in a position to influence preferentially the activity of the SN and PpTd of the basal ganglia via an excitatory, glutamatergic input. PMID:14689481

  6. Vascular Risk Factors and Diseases Modulate Deficits of Reward-Based Reversal Learning in Acute Basal Ganglia Stroke

    PubMed Central

    Wicking, Manon; Bellebaum, Christian; Hermann, Dirk M.

    2016-01-01

    Background Besides motor function, the basal ganglia have been implicated in feedback learning. In patients with chronic basal ganglia infarcts, deficits in reward-based reversal learning have previously been described. Methods We re-examined the acquisition and reversal of stimulus-stimulus-reward associations and acquired equivalence in eleven patients with acute basal ganglia stroke (8 men, 3 women; 57.8±13.3 years), whose performance was compared eleven healthy subjects of comparable age, sex distribution and education, who were recruited outside the hospital. Eleven hospitalized patients with a similar vascular risk profile as the stroke patients but without stroke history served as clinical control group. Results In a neuropsychological assessment 7±3 days post-stroke, verbal and spatial short-term and working memory and inhibition control did not differ between groups. Compared with healthy subjects, control patients with vascular risk factors exhibited significantly reduced performance in the reversal phase (F[2,30] = 3.47; p = 0.044; post-hoc comparison between risk factor controls and healthy controls: p = 0.030), but not the acquisition phase (F[2,30] = 1.01; p = 0.376) and the acquired equivalence (F[2,30] = 1.04; p = 0.367) tasks. In all tasks, the performance of vascular risk factor patients closely resembled that of basal ganglia stroke patients. Correlation studies revealed a significant association of the number of vascular risk factors with reversal learning (r = -0.33, p = 0.012), but not acquisition learning (r = -0.20, p = 0.121) or acquired equivalence (r = -0.22, p = 0.096). Conclusions The previously reported impairment of reward-based learning may be attributed to vascular risk factors and associated diseases, which are enriched in stroke patients. This study emphasizes the necessity of appropriate control subjects in cognition studies. PMID:27163585

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

    PubMed Central

    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. PMID:26640481

  8. 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. PMID:26640481

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

    PubMed

    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

  10. 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

  11. Pineal ganglioglioma in a patient with familial basal ganglia calcification and elevated serum alpha-fetoprotein: case report.

    PubMed

    Tokoro, K; Chiba, Y; Ohtani, T; Abe, H; Yagishita, S

    1993-09-01

    Pineal ganglioglioma was diagnosed in a 36-year-old man with familial basal ganglia calcification and elevated serum alpha-fetoprotein. The patient was treated surgically with a good result. Only four other cases of this tumor have been reported. His 38-year-old brother also showed basal ganglia calcification and elevated serum chorionic gonadotropin as well as alpha-fetoprotein. Familial basal ganglia calcification with elevated serum alpha-fetoprotein in a nonhepatic benign condition is rare. The pathogenesis of these conditions is discussed. PMID:7692346

  12. 3-Hydroxy-3-methylglutaric aciduria with bilateral basal ganglia lesion: A case report

    PubMed Central

    HAO, XIAOSHENG; WANG, JIANGTAO; LIU, SONGYAN; CHEN, YINBO; ZHANG, YAN; HAO, YUNPENG

    2016-01-01

    3-Hydroxy-3-methylglutaric aciduria (3-HMG, OMIN 246450) is a rare autosomal recessive metabolic disorder caused by a deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase, a key enzyme in leucine metabolism and ketone body synthesis. Acute episodes of 3-HMG may be triggered by fasting or infection, and symptoms include vomiting, diarrhea, lethargy and hypotonia. If left untreated, prolonged hypoglycemia and metabolic acidosis may cause breathing problems, seizures, and coma. In addition, 3-HMG is associated with damage to the central nervous system, and there are several reports of white matter abnormality or cerebral atrophy. The presence of bilateral basal ganglia damage in 3-HMG has been rarely reported. Here, we present a case report of a 20-month old male with severe 3-HMG and prominent bilateral lesions in the basal ganglia. PMID:27284350

  13. Chronic 5-HT transporter blockade reduces DA signaling to elicit basal ganglia dysfunction.

    PubMed

    Morelli, Emanuela; Moore, Holly; Rebello, Tahilia J; Gray, Neil; Steele, Kelly; Esposito, Ennio; Gingrich, Jay A; Ansorge, Mark S

    2011-11-01

    Serotonin (5-HT)-selective reuptake inhibitors (SSRIs) are widely administered for the treatment of depression, anxiety, and other neuropsychiatric disorders, but response rates are low, and side effects often lead to discontinuation. Side effect profiles suggest that SSRIs inhibit dopaminergic activity, but mechanistic insight remains scarce. Here we show that in mice, chronic 5-HT transporter (5-HTT) blockade during adulthood but not during development impairs basal ganglia-dependent behaviors in a dose-dependent and reversible fashion. Furthermore, chronic 5-HTT blockade reduces striatal dopamine (DA) content and metabolism. A causal relationship between reduced DA signaling and impaired basal ganglia-dependent behavior is indicated by the reversal of behavioral deficits through L-DOPA administration. Our data suggest that augmentation of DA signaling would reduce side effects and increase efficacies of SSRI-based therapy. PMID:22049417

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

    SciTech Connect

    Akiyama, H.; Harrop, R.; McGeer, P.L.; Peppard, R.; McGeer, E.G.

    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, 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.

  15. Rem2, a member of the RGK family of small GTPases, is enriched in nuclei of the basal ganglia.

    PubMed

    Liput, Daniel J; Lu, Van B; Davis, Margaret I; Puhl, Henry L; Ikeda, Stephen R

    2016-01-01

    Rem2 is a member of the RGK subfamily of RAS small GTPases. Rem2 inhibits high voltage activated calcium channels, is involved in synaptogenesis, and regulates dendritic morphology. Rem2 is the primary RGK protein expressed in the nervous system, but to date, the precise expression patterns of this protein are unknown. In this study, we characterized Rem2 expression in the mouse nervous system. In the CNS, Rem2 mRNA was detected in all regions examined, but was enriched in the striatum. An antibody specific for Rem2 was validated using a Rem2 knockout mouse model and used to show abundant expression in striatonigral and striatopallidal medium spiny neurons but not in several interneuron populations. In the PNS, Rem2 was abundant in a subpopulation of neurons in the trigeminal and dorsal root ganglia, but was absent in sympathetic neurons of superior cervical ganglia. Under basal conditions, Rem2 was subject to post-translational phosphorylation, likely at multiple residues. Further, Rem2 mRNA and protein expression peaked at postnatal week two, which corresponds to the period of robust neuronal maturation in rodents. This study will be useful for elucidating the functions of Rem2 in basal ganglia physiology. PMID:27118437

  16. Rem2, a member of the RGK family of small GTPases, is enriched in nuclei of the basal ganglia

    PubMed Central

    Liput, Daniel J.; Lu, Van B.; Davis, Margaret I.; Puhl, Henry L.; Ikeda, Stephen R.

    2016-01-01

    Rem2 is a member of the RGK subfamily of RAS small GTPases. Rem2 inhibits high voltage activated calcium channels, is involved in synaptogenesis, and regulates dendritic morphology. Rem2 is the primary RGK protein expressed in the nervous system, but to date, the precise expression patterns of this protein are unknown. In this study, we characterized Rem2 expression in the mouse nervous system. In the CNS, Rem2 mRNA was detected in all regions examined, but was enriched in the striatum. An antibody specific for Rem2 was validated using a Rem2 knockout mouse model and used to show abundant expression in striatonigral and striatopallidal medium spiny neurons but not in several interneuron populations. In the PNS, Rem2 was abundant in a subpopulation of neurons in the trigeminal and dorsal root ganglia, but was absent in sympathetic neurons of superior cervical ganglia. Under basal conditions, Rem2 was subject to post-translational phosphorylation, likely at multiple residues. Further, Rem2 mRNA and protein expression peaked at postnatal week two, which corresponds to the period of robust neuronal maturation in rodents. This study will be useful for elucidating the functions of Rem2 in basal ganglia physiology. PMID:27118437

  17. 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. PMID:25514960

  18. Responses of the Rat Basal Ganglia Neurotensin Systems to Low Doses of Methamphetamine

    PubMed Central

    Alburges, Mario E.; Hoonakker, Amanda J.; Cordova, Nathaniel M.; Robson, Christina M.; McFadden, Lisa M.; Martin, Amber L.; Hanson, Glen R.

    2014-01-01

    Rationale Administration of high doses of methamphetamine (METH) in a manner mimicking the bingeing patterns associated with abuse, reduces NT release and causes its accumulation and elevated NT levels in extrapyramidal structures by a D1 mechanism. The relevance of these findings to the therapeutic use of METH needs to be studied. Objectives The effect of low doses (comparable to that used for therapy) of METH on basal ganglia NT systems was examined and compared to high-dose and self-administration effects previously reported. Methods Rats were injected four times (2-h intervals) with either saline or low doses of METH (0.25, 0.50 or 1.00 mg/kg/s.c.). For the DA antagonist studies, animals were pretreated with a D1 (SCH23390) or D2 (eticlopride) antagonist 15 min prior to METH or saline treatments. Rats were sacrificed 5–48 h after last injection. Results METH at doses of 0.25 and 0.50, but not 1.00 mg/kg rapidly and briefly decreased NTLI concentration in all basal ganglia structures studied. In the posterior dorsal striatum, the reduction in NT level after low-dose METH appeared to be caused principally by D2 stimulation, but both D2 and D1 stimulation were required for the NT responses in the other basal ganglia regions. Conclusions A novel finding from the present study was that opposite to abuse-mimicking high doses of METH, the therapeutically relevant low-dose METH treatment reduced NT tissue levels likely reflecting an increase in NT release and a short-term depletion of the levels of this neuropeptide in basal ganglia structures. The possible significance is discussed. PMID:24522333

  19. The basal ganglia select the expected sensory input used for predictive coding

    PubMed Central

    Colder, Brian

    2015-01-01

    While considerable evidence supports the notion that lower-level interpretation of incoming sensory information is guided by top-down sensory expectations, less is known about the source of the sensory expectations or the mechanisms by which they are spread. Predictive coding theory proposes that sensory expectations flow down from higher-level association areas to lower-level sensory cortex. A separate theory of the role of prediction in cognition describes “emulations” as linked representations of potential actions and their associated expected sensation that are hypothesized to play an important role in many aspects of cognition. The expected sensations in active emulations are proposed to be the top-down expectation used in predictive coding. Representations of the potential action and expected sensation in emulations are claimed to be instantiated in distributed cortical networks. Combining predictive coding with emulations thus provides a theoretical link between the top-down expectations that guide sensory expectations and the cortical networks representing potential actions. Now moving to theories of action selection, the basal ganglia has long been proposed to select between potential actions by reducing inhibition to the cortical network instantiating the desired action plan. Integration of these isolated theories leads to the novel hypothesis that reduction in inhibition from the basal ganglia selects not just action plans, but entire emulations, including the sensory input expected to result from the action. Basal ganglia disinhibition is hypothesized to both initiate an action and also allow propagation of the action’s associated sensory expectation down towards primary sensory cortex. This is a novel proposal for the role of the basal ganglia in biasing perception by selecting the expected sensation, and initiating the top-down transmission of those expectations in predictive coding. PMID:26441627

  20. Two Case Reports on Thalamic and Basal Ganglia Involvement in Children with Dengue Fever

    PubMed Central

    Adhikari, Lihini; Wijesekera, Saraji; Wijayawardena, Maheshaka; Chandrasiri, Suchithra

    2016-01-01

    There have been increasing numbers of case reports of dengue infection with unusual manifestations. Such unusual manifestations including acute liver failure and encephalopathy could be manifested even in the absence of significant plasma leakage. Further, severe organ involvement including nervous system involvement indicates severe dengue infection. However, neurological manifestations of dengue fever are rare. This is the first case report of dengue infection with thalamic and basal ganglia involvement in Sri Lanka. PMID:27478661

  1. Basal ganglia T1 hyperintensity in LGI1-autoantibody faciobrachial dystonic seizures

    PubMed Central

    Kotsenas, Amy L.; Britton, Jeffrey W.; McKeon, Andrew; Watson, Robert E.; Klein, Christopher J.; Boeve, Bradley F.; Lowe, Val; Ahlskog, J. Eric; Shin, Cheolsu; Boes, Christopher J.; Crum, Brian A.; Laughlin, Ruple S.; Pittock, Sean J.

    2015-01-01

    Objective: To characterize the clinical features and MRI abnormalities of leucine-rich glioma-inactivated 1 (LGI1)-autoantibody (Ab) faciobrachial dystonic seizures (FBDS). Methods: Forty-eight patients with LGI1-Ab encephalopathy were retrospectively identified by searching our clinical and serologic database from January 1, 2002, to June 1, 2015. Of these, 26 met inclusion criteria for this case series: LGI1-Ab seropositivity and FBDS. In a separate analysis of all 48 patients initially identified, the MRIs of patients with (n = 26) and without (n = 22) FBDS were compared by 2 neuroradiologists blinded to the clinical details. Results: The median age of the 26 included patients was 62.5 years (range 37–78); 65% were men. FBDS involved arm (26), face (22), and leg (12). Ten were previously diagnosed as psychogenic. Ictal EEGs were normal in 20 of 23 assessed. Basal ganglia T1 and T2 signal abnormalities were detected in 11 patients (42%), with excellent agreement between neuroradiologists (κ scores of 0.86 and 0.93, respectively), and included T1 hyperintensity alone (2), T2 hyperintensity alone (1), or both (8). The T1 hyperintensities persisted longer than the T2 hyperintensities (median 11 weeks vs 1 week, p = 0.02). Improvement with immunotherapy (18/18) was more frequent than with antiepileptic medications (10/24). A separate analysis of all 48 patients initially identified with LGI1-Ab encephalopathy showed that basal ganglia MRI abnormalities were present in 11 of 26 with FBDS but not present in those without FBDS (0/22) (p < 0.001). In contrast, mesial temporal MRI abnormalities were less common among those with FBDS (42%) than those without (91%) (p < 0.001). Conclusions: Basal ganglia T1 hyperintensity is a clinically useful MRI biomarker of LGI1-Ab FBDS and suggests a basal ganglia localization. PMID:26468474

  2. Two Case Reports on Thalamic and Basal Ganglia Involvement in Children with Dengue Fever.

    PubMed

    Liyanage, Guwani; Adhikari, Lihini; Wijesekera, Saraji; Wijayawardena, Maheshaka; Chandrasiri, Suchithra

    2016-01-01

    There have been increasing numbers of case reports of dengue infection with unusual manifestations. Such unusual manifestations including acute liver failure and encephalopathy could be manifested even in the absence of significant plasma leakage. Further, severe organ involvement including nervous system involvement indicates severe dengue infection. However, neurological manifestations of dengue fever are rare. This is the first case report of dengue infection with thalamic and basal ganglia involvement in Sri Lanka. PMID:27478661

  3. 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

  4. Integration of reinforcement learning and optimal decision-making theories of the basal ganglia.

    PubMed

    Bogacz, Rafal; Larsen, Tobias

    2011-04-01

    This article seeks to integrate two sets of theories describing action selection in the basal ganglia: reinforcement learning theories describing learning which actions to select to maximize reward and decision-making theories proposing that the basal ganglia selects actions on the basis of sensory evidence accumulated in the cortex. In particular, we present a model that integrates the actor-critic model of reinforcement learning and a model assuming that the cortico-basal-ganglia circuit implements a statistically optimal decision-making procedure. The values of cortico-striatal weights required for optimal decision making in our model differ from those provided by standard reinforcement learning models. Nevertheless, we show that an actor-critic model converges to the weights required for optimal decision making when biologically realistic limits on synaptic weights are introduced. We also describe the model's predictions concerning reaction times and neural responses during learning, and we discuss directions required for further integration of reinforcement learning and optimal decision-making theories. PMID:21222528

  5. 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. PMID:21945835

  6. Modulation of the basal ganglia dopaminergic system in a transgenic mouse exhibiting dystonia-like features

    PubMed Central

    Giannakopoulou, D.; Armata, I. A.; Mitsacos, A.; Shashidharan, P.; Giompres, P.

    2011-01-01

    Dystonia is a movement disorder characterized by involuntary excessive muscle activity and abnormal postures. There are data supporting the hypothesis that basal ganglia dysfunction, and specifically dopaminergic system dysfunction, plays a role in dystonia. In the present study, we used hyperkinetic transgenic mice generated as a model of DYT1 dystonia and compared the basal ganglia dopaminergic system between transgenic mice exhibiting hyperkinesia (affected) transgenic mice not showing movement abnormalities (unaffected), and non-transgenic littermates A decrease in the density of striatal D2 binding sites, measured by [3H]raclopride binding, and D2 mRNA expression in substantia nigra pars compacta (SNpc) was revealed in affected an unaffected transgenic mice when compared with non-transgenic. No difference in D1 receptor binding and DAT binding, measured by [3H]SCH23390 and [3H]WIN35428 binding, respectively, was found in striatum of transgenic animals. In SNpc, increased levels of DAT binding sites were observed in affected and unaffected animals compared to non-transgenic, whereas no change in DAT mRNA expression was found. Our results show selective neurochemical changes in the basal ganglia dopaminergic system, suggesting a possible involvement in the pathophysiology of dystonialike motor hyperactivity. PMID:21136125

  7. Supplementary motor area and presupplementary motor area: targets of basal ganglia and cerebellar output.

    PubMed

    Akkal, Dalila; Dum, Richard P; Strick, Peter L

    2007-10-01

    We used retrograde transneuronal transport of neurotropic viruses in Cebus monkeys to examine the organization of basal ganglia and cerebellar projections to two cortical areas on the medial wall of the hemisphere, the supplementary motor area (SMA) and the pre-SMA. We found that both of these cortical areas are the targets of disynaptic projections from the dentate nucleus of the cerebellum and from the internal segment of the globus pallidus (GPi). On average, the number of pallidal neurons that project to the SMA and pre-SMA is approximately three to four times greater than the number of dentate neurons that project to these cortical areas. GPi neurons that project to the pre-SMA are located in a rostral, "associative" territory of the nucleus, whereas GPi neurons that project to the SMA are located in a more caudal and ventral "sensorimotor" territory. Similarly, dentate neurons that project to the pre-SMA are located in a ventral, "nonmotor" domain of the nucleus, whereas dentate neurons that project to the SMA are located in a more dorsal, "motor" domain. The differential origin of subcortical projections to the SMA and pre-SMA suggests that these cortical areas are nodes in distinct neural systems. Although both systems are the target of outputs from the basal ganglia and the cerebellum, these two cortical areas seem to be dominated by basal ganglia input. PMID:17913900

  8. Basal Ganglia Dopamine Loss Due to Defect in Purine Recycling

    PubMed Central

    Egami, Kiyoshi; Yitta, Silaja; Kasim, Suhail; Lewers, J. Chris; Roberts, Rosalinda C.; Lehar, Mohamed; Jinnah, H. A.

    2007-01-01

    Several rare inherited disorders have provided valuable experiments of nature highlighting specific biological processes of particular importance to the survival or function of midbrain dopamine neurons. In both humans and mice, deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) is associated with profound loss of striatal dopamine, with relative preservation of other neurotransmitters. In the current studies of knockout mice, no morphological signs of abnormal development or degeneration were found in an exhaustive battery that included stereological and morphometric measures of midbrain dopamine neurons, electron microscopic studies of striatal axons and terminals, and stains for degeneration or gliosis. A novel culture model involving HPRT-deficient dopaminergic neurons also exhibited significant loss of dopamine without a morphological correlate. These results suggest dopamine loss in HPRT deficiency has a biochemical rather than anatomical basis, and imply purine recycling to be a biochemical process of particular importance to the function of dopaminergic neurons. PMID:17374562

  9. Making working memory work: a computational model of learning in the prefrontal cortex and basal ganglia.

    PubMed

    O'Reilly, Randall C; Frank, Michael J

    2006-02-01

    The prefrontal cortex has long been thought to subserve both working memory (the holding of information online for processing) and executive functions (deciding how to manipulate working memory and perform processing). Although many computational models of working memory have been developed, the mechanistic basis of executive function remains elusive, often amounting to a homunculus. This article presents an attempt to deconstruct this homunculus through powerful learning mechanisms that allow a computational model of the prefrontal cortex to control both itself and other brain areas in a strategic, task-appropriate manner. These learning mechanisms are based on subcortical structures in the midbrain, basal ganglia, and amygdala, which together form an actor-critic architecture. The critic system learns which prefrontal representations are task relevant and trains the actor, which in turn provides a dynamic gating mechanism for controlling working memory updating. Computationally, the learning mechanism is designed to simultaneously solve the temporal and structural credit assignment problems. The model's performance compares favorably with standard backpropagation-based temporal learning mechanisms on the challenging 1-2-AX working memory task and other benchmark working memory tasks. PMID:16378516

  10. Behavioural aspects of a modified crosstalk between basal ganglia and limbic system in Parkinson's disease.

    PubMed

    Gyorfi, Orsolya; Nagy, Helga; Bokor, Magdolna; Keri, Szabolcs

    2016-06-01

    Dysfunctions in dopaminergic neurotransmission lead to motor symptoms and cognitive impairments associated with behavioural disturbances. Parkinson's disease is a neurodegenerative disorder which is primarily characterized by an abnormal basal ganglia activity. Recently, increased attention has been directed towards the hippocampus in the development of non-motor symptoms. Given the temporal progression of the disease, dopaminergic depletion firstly affects the dorsal striatum leaving the ventral striatum relatively intact. However, it is possible that the structure and function of the hippocampus shows alterations even in early stages of Parkinson's disease. Subtle cognitive impairments occur in the earliest stages, and therefore Parkinson's disease could provide a unique model to investigate the effect of replacement therapies on a neural network with different baseline dopaminergic levels. Strong evidence suggests that dopaminergic medications improve the motor symptoms, but these medications might have disadvantageous effects on cognitive functions. In this review, we examine the role of dopaminergic changes across several cognitive and behavioural impairments observed in Parkinson's disease, with a special reference to hippocampal dysfunctions. PMID:27390205

  11. Cost-efficient FPGA implementation of basal ganglia and their Parkinsonian analysis.

    PubMed

    Yang, Shuangming; Wang, Jiang; Li, Shunan; Deng, Bin; Wei, Xile; Yu, Haitao; Li, Huiyan

    2015-11-01

    The basal ganglia (BG) comprise multiple subcortical nuclei, which are responsible for cognition and other functions. Developing a brain-machine interface (BMI) demands a suitable solution for the real-time implementation of a portable BG. In this study, we used a digital hardware implementation of a BG network containing 256 modified Izhikevich neurons and 2048 synapses to reliably reproduce the biological characteristics of BG on a single field programmable gate array (FPGA) core. We also highlighted the role of Parkinsonian analysis by considering neural dynamics in the design of the hardware-based architecture. Thus, we developed a multi-precision architecture based on a precise analysis using the FPGA-based platform with fixed-point arithmetic. The proposed embedding BG network can be applied to intelligent agents and neurorobotics, as well as in BMI projects with clinical applications. Although we only characterized the BG network with Izhikevich models, the proposed approach can also be extended to more complex neuron models and other types of functional networks. PMID:26318085

  12. Extensive Direct Subcortical Cerebellum-Basal Ganglia Connections in Human Brain as Revealed by Constrained Spherical Deconvolution Tractography

    PubMed Central

    Milardi, Demetrio; Arrigo, Alessandro; Anastasi, Giuseppe; Cacciola, Alberto; Marino, Silvia; Mormina, Enricomaria; Calamuneri, Alessandro; Bruschetta, Daniele; Cutroneo, Giuseppina; Trimarchi, Fabio; Quartarone, Angelo

    2016-01-01

    The connections between the cerebellum and basal ganglia were assumed to occur at the level of neocortex. However evidences from animal data have challenged this old perspective showing extensive subcortical pathways linking the cerebellum with the basal ganglia. Here we tested the hypothesis if these connections also exist between the cerebellum and basal ganglia in the human brain by using diffusion magnetic resonance imaging and tractography. Fifteen healthy subjects were analyzed by using constrained spherical deconvolution technique obtained with a 3T magnetic resonance imaging scanner. We found extensive connections running between the subthalamic nucleus and cerebellar cortex and, as novel result, we demonstrated a direct route linking the dentate nucleus to the internal globus pallidus as well as to the substantia nigra. These findings may open a new scenario on the interpretation of basal ganglia disorders. PMID:27047348

  13. Extensive Direct Subcortical Cerebellum-Basal Ganglia Connections in Human Brain as Revealed by Constrained Spherical Deconvolution Tractography.

    PubMed

    Milardi, Demetrio; Arrigo, Alessandro; Anastasi, Giuseppe; Cacciola, Alberto; Marino, Silvia; Mormina, Enricomaria; Calamuneri, Alessandro; Bruschetta, Daniele; Cutroneo, Giuseppina; Trimarchi, Fabio; Quartarone, Angelo

    2016-01-01

    The connections between the cerebellum and basal ganglia were assumed to occur at the level of neocortex. However evidences from animal data have challenged this old perspective showing extensive subcortical pathways linking the cerebellum with the basal ganglia. Here we tested the hypothesis if these connections also exist between the cerebellum and basal ganglia in the human brain by using diffusion magnetic resonance imaging and tractography. Fifteen healthy subjects were analyzed by using constrained spherical deconvolution technique obtained with a 3T magnetic resonance imaging scanner. We found extensive connections running between the subthalamic nucleus and cerebellar cortex and, as novel result, we demonstrated a direct route linking the dentate nucleus to the internal globus pallidus as well as to the substantia nigra. These findings may open a new scenario on the interpretation of basal ganglia disorders. PMID:27047348

  14. Evolution of the basal ganglia: new perspectives through a comparative approach

    PubMed Central

    SMEETS, WILHELMUS J. A. J.; MARÍN, OSCAR; GONZÁLEZ, AGUSTÍN

    2000-01-01

    The basal ganglia (BG) have received much attention during the last 3 decades mainly because of their clinical relevance. Our understanding of their structure, organisation and function in terms of chemoarchitecture, compartmentalisation, connections and receptor localisation has increased equally. Most of the research has been focused on the mammalian BG, but a considerable number of studies have been carried out in nonmammalian vertebrates, in particular reptiles and birds. The BG of the latter 2 classes of vertebrates, which together with mammals constitute the amniotic vertebrates, have been thoroughly studied by means of tract-tracing and immunohistochemical techniques. The terminology used for amniotic BG structures has frequently been adopted to indicate putative corresponding structures in the brain of anamniotes, i.e. amphibians and fishes, but data for such a comparison were, until recently, almost totally lacking. It has been proposed several times that the occurrence of well developed BG structures probably constitutes a landmark in the anamniote-amniote transition. However, our recent studies of connections, chemoarchitecture and development of the basal forebrain of amphibians have revealed that tetrapod vertebrates share a common pattern of BG organisation. This pattern includes the existence of dorsal and ventral striatopallidal systems, reciprocal connections between the striatopallidal complex and the diencephalic and mesencephalic basal plate (striatonigral and nigrostriatal projections), and descending pathways from the striatopallidal system to the midbrain tectum and reticular formation. The connectional similarities are paralleled by similarities in the distribution of chemical markers of striatal and pallidal structures such as dopamine, substance P and enkephalin, as well as by similarities in development and expression of homeobox genes. On the other hand, a major evolutionary trend is the progressive involvement of the cortex in the

  15. Model-based action planning involves cortico-cerebellar and basal ganglia networks.

    PubMed

    Fermin, Alan S R; Yoshida, Takehiko; Yoshimoto, Junichiro; Ito, Makoto; Tanaka, Saori C; Doya, Kenji

    2016-01-01

    Humans can select actions by learning, planning, or retrieving motor memories. Reinforcement Learning (RL) associates these processes with three major classes of strategies for action selection: exploratory RL learns state-action values by exploration, model-based RL uses internal models to simulate future states reached by hypothetical actions, and motor-memory RL selects past successful state-action mapping. In order to investigate the neural substrates that implement these strategies, we conducted a functional magnetic resonance imaging (fMRI) experiment while humans performed a sequential action selection task under conditions that promoted the use of a specific RL strategy. The ventromedial prefrontal cortex and ventral striatum increased activity in the exploratory condition; the dorsolateral prefrontal cortex, dorsomedial striatum, and lateral cerebellum in the model-based condition; and the supplementary motor area, putamen, and anterior cerebellum in the motor-memory condition. These findings suggest that a distinct prefrontal-basal ganglia and cerebellar network implements the model-based RL action selection strategy. PMID:27539554

  16. 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. PMID:25642805

  17. A hypothesis for basal ganglia-dependent reinforcement learning in the songbird

    PubMed Central

    Fee, Michale S.; Goldberg, Jesse H.

    2011-01-01

    Most of our motor skills are not innately programmed, but are learned by a combination of motor exploration and performance evaluation, suggesting that they proceed through a reinforcement learning (RL) mechanism. Songbirds have emerged as a model system to study how a complex behavioral sequence can be learned through an RL-like strategy. Interestingly, like motor sequence learning in mammals, song learning in birds requires a basal ganglia (BG)-thalamocortical loop, suggesting common neural mechanisms. Here we outline a specific working hypothesis for how BG-forebrain circuits could utilize an internally computed reinforcement signal to direct song learning. Our model includes a number of general concepts borrowed from the mammalian BG literature, including a dopaminergic reward prediction error and dopamine mediated plasticity at corticostriatal synapses. We also invoke a number of conceptual advances arising from recent observations in the songbird. Specifically, there is evidence for a specialized cortical circuit that adds trial-to-trial variability to stereotyped cortical motor programs, and a role for the BG in ‘biasing’ this variability to improve behavioral performance. This BG-dependent ‘premotor bias’ may in turn guide plasticity in downstream cortical synapses to consolidate recently-learned song changes. Given the similarity between mammalian and songbird BG-thalamocortical circuits, our model for the role of the BG in this process may have broader relevance to mammalian BG function. PMID:22015923

  18. 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

  19. Model-based action planning involves cortico-cerebellar and basal ganglia networks

    PubMed Central

    Fermin, Alan S. R.; Yoshida, Takehiko; Yoshimoto, Junichiro; Ito, Makoto; Tanaka, Saori C.; Doya, Kenji

    2016-01-01

    Humans can select actions by learning, planning, or retrieving motor memories. Reinforcement Learning (RL) associates these processes with three major classes of strategies for action selection: exploratory RL learns state-action values by exploration, model-based RL uses internal models to simulate future states reached by hypothetical actions, and motor-memory RL selects past successful state-action mapping. In order to investigate the neural substrates that implement these strategies, we conducted a functional magnetic resonance imaging (fMRI) experiment while humans performed a sequential action selection task under conditions that promoted the use of a specific RL strategy. The ventromedial prefrontal cortex and ventral striatum increased activity in the exploratory condition; the dorsolateral prefrontal cortex, dorsomedial striatum, and lateral cerebellum in the model-based condition; and the supplementary motor area, putamen, and anterior cerebellum in the motor-memory condition. These findings suggest that a distinct prefrontal-basal ganglia and cerebellar network implements the model-based RL action selection strategy. PMID:27539554

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

    PubMed

    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

  1. Novel signal-dependent filter bank method for identification of multiple basal ganglia nuclei in Parkinsonian patients

    NASA Astrophysics Data System (ADS)

    Pinzon-Morales, R. D.; Orozco-Gutierrez, A. A.; Castellanos-Dominguez, G.

    2011-06-01

    Microelectrode recordings are a valuable tool for assisting localization targets during deep brain stimulation procedures in Parkinson's disease neurosurgery. Attempts to automate and standardize this process have been limited by variability in patient neurophysiology and strong dynamics of microelectrode recordings. In this paper, a methodology for the identification of basal ganglia nuclei is presented that is based on a signal-dependent filter bank method using microelectrode recordings. The method is a customized realization of the discrete wavelet transform via the lifting scheme that is optimally tuned by genetic algorithms. Using this method, unique mother wavelet functions that exhibit an adaptable spectrum to the microelectrode recording dynamic are generated. Additionally, by extracting morphological features from the space-transformed microelectrode recording, it is possible to integrate them into three-dimensional (3D) feature spaces with maximum class separability. Finally, high discriminant feature spaces are fed into basic classifiers to recognize up to four basal nuclei. Comparison with several existing wavelets highlights the characteristics of new mother wavelets. Additionally, classification results show that identification of addressed nuclei in the basal ganglia can be performed with 95% confidence.

  2. 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

    2011-01-01

    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. PMID:22832400

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

    PubMed

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

    2016-02-15

    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

  4. A toxic fraction from scolopendra venom increases the basal release of neurotransmitters in the ventral ganglia of crustaceans.

    PubMed

    Gutiérrez, María del Carmen; Abarca, Carolina; Possani, Lourival D

    2003-06-01

    A toxic fraction from centipede (Scolopendra sp.) venom was tested in neurotransmitter release experiments. The venom was fractionated by DEAE-cellulose with a linear gradient from 20 mM to 1.0 M of ammonium acetate pH 4.7. Lethality tests were performed by injections into the third abdominal dorsolateral segment of sweet water crayfishes of the species Cambarellus cambarellus. Only fraction V (TF) was toxic. Analysis by SDS-PAGE showed that this fraction contains at least seven proteins. It induces an increase of basal gamma-amino butyric acid (GABA) and glutamate release from ventral abdominal ganglia of C. cambarellus. Assays conducted with this fraction in the presence of several drugs that affect ion channel function suggested that TF modifies membrane permeability by increasing basal release of neurotransmitters was very likely through sodium channels. PMID:12860060

  5. A selective role for right insula—basal ganglia circuits in appetitive stimulus processing

    PubMed Central

    Vijayaraghavan, Lavanya; Adolphs, Ralph; Kennedy, Daniel P.; Cassell, Martin; Tranel, Daniel; Paradiso, Sergio

    2013-01-01

    Hemispheric lateralization of hedonic evaluation (‘liking’) and incentive motivation (‘wanting’) in neural networks connecting the basal ganglia and insula (BG-I) in humans was examined. Participants with brain damage restricted to the BG-I of the right (n = 5) or left (n = 5) hemisphere, and 26 healthy participants matched on age, sex and intelligence quotient were tested on positively and negatively valenced pictures drawn from varied stimulus categories (Vijayaraghavan et al., 2008). Liking was assessed with explicit ratings of pleasantness using a nine-point Likert scale. Wanting was quantified as the amount of work (via repeated keypresses) that participants expended to increase (approach) or decrease (withdraw) viewing time. Right-lesion patients showed abnormally low viewing times and liking ratings for positive images. For a subset of positive images depicting sexual content, right-lesion patients exhibited active withdrawal, while the other two groups approached such stimuli. These results suggest that the right basal ganglia–insula complex plays a greater role than the left in supporting hedonic evaluation and motivational approach to positively valenced stimuli. The finding that active avoidance of stimuli that were not ‘liked’ was spared in both right- and left-sided lesion subjects suggests that unilateral damage to insula/basal ganglia circuits may not be sufficient to affect general incentive motivation independent of preference. PMID:22798397

  6. Incomplete and Inaccurate Vocal Imitation after Knockdown of FoxP2 in Songbird Basal Ganglia Nucleus Area X

    PubMed Central

    Haesler, Sebastian; Rochefort, Christelle; Georgi, Benjamin; Licznerski, Pawel; Osten, Pavel; Scharff, Constance

    2007-01-01

    The gene encoding the forkhead box transcription factor, FOXP2, is essential for developing the full articulatory power of human language. Mutations of FOXP2 cause developmental verbal dyspraxia (DVD), a speech and language disorder that compromises the fluent production of words and the correct use and comprehension of grammar. FOXP2 patients have structural and functional abnormalities in the striatum of the basal ganglia, which also express high levels of FOXP2. Since human speech and learned vocalizations in songbirds bear behavioral and neural parallels, songbirds provide a genuine model for investigating the basic principles of speech and its pathologies. In zebra finch Area X, a basal ganglia structure necessary for song learning, FoxP2 expression increases during the time when song learning occurs. Here, we used lentivirus-mediated RNA interference (RNAi) to reduce FoxP2 levels in Area X during song development. Knockdown of FoxP2 resulted in an incomplete and inaccurate imitation of tutor song. Inaccurate vocal imitation was already evident early during song ontogeny and persisted into adulthood. The acoustic structure and the duration of adult song syllables were abnormally variable, similar to word production in children with DVD. Our findings provide the first example of a functional gene analysis in songbirds and suggest that normal auditory-guided vocal motor learning requires FoxP2. PMID:18052609

  7. Basal ganglia morphometry and repetitive behavior in young children with autism spectrum disorder

    PubMed Central

    Estes, Annette; Shaw, Dennis W. W.; Sparks, Bobbi F.; Friedman, Seth; Giedd, Jay N.; Dawson, Geraldine; Bryan, Matthew; Dager, Stephen R.

    2011-01-01

    Scientific Abstract We investigated repetitive and stereotyped behavior (RSB) and its relationship to morphometric measures of the basal ganglia and thalami in 3-4 year old children with autism spectrum disorder (ASD; n=77) and developmental delay without autism (DD; n=34). Children were assessed through clinical evaluation and parent report using RSB-specific scales extracted from the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview, and the Aberrant Behavior Checklist. A subset of children with ASD (n=45), DD (n=14) and a group of children with typical development (TD; n=25) were also assessed by magnetic resonance imaging (MRI). Children with ASD demonstrated elevated RSB across all measures compared to children with DD. Enlargement of the left and right striatum, more specifically the left and right putamen, and left caudate, was observed in the ASD compared to the TD group. However, nuclei were not significantly enlarged after controlling for cerebral volume. The DD group, in comparison to the ASD group, demonstrated smaller thalami and basal ganglia regions even when scaled for cerebral volume, with the exception of the left striatum, left putamen, and right putamen. Elevated RSB, as measured by the ADOS, was associated with decreased volumes in several brain regions: left thalamus, right globus pallidus, left and right putamen, right striatum and a trend for left globus pallidus and left striatum within the ASD group. These results confirm earlier reports that RSB is common early in the clinical course of ASD and, furthermore, demonstrate that such behaviors may be associated with decreased volumes of the basal ganglia and thalamus. PMID:21480545

  8. Depression does not influence basal ganglia-mediated psychomotor speed in HIV-1 infection.

    PubMed

    von Giesen, H J; Bäcker, R; Hefter, H; Arendt, G

    2001-01-01

    The authors examined the effects of depressive mood (Hamilton Rating Scale for Depression [Ham-D]) on basal ganglia-mediated psychomotor speed (motor test battery) in 202 HIV-1 seropositive homosexual males with no prior history of antiretroviral treatment. HIV-1 seropositive patients showed a significant slowing of most rapid alternating movements (MRAM) and significantly prolonged contraction times (CT) compared with 66 HIV-1 seronegative male control subjects. Factor analysis of Ham-D scores isolated a factor containing the items depressed mood, suicide, and psychic and somatic anxiety. This factor did not correlate with MRAM or CT. Depression and psychomotor speed are independent in HIV-1infection. PMID:11207334

  9. Isolated symmetrical bilateral basal ganglia T2 hyperintensity in carbon monoxide poisoning.

    PubMed

    Subhaschandra, S; Jatishwor, W; Suraj, Th

    2008-10-01

    Carbon monoxide poisoning is not uncommon during the winter months. To make a diagnosis, strong clinical suspicion and acumen, and history of the exposure are necessary. Many a time, the presenting complaints may fail to help reach a diagnosis, in the absence of history. Imaging plays a role in the diagnosis of brain injury with the characteristic features, which are correlated with the clinical profile. Isolated bilateral basal ganglia injury revealing T2 hyperintensity in MRI may be observed in acute carbon monoxide poisoning. PMID:19893684

  10. [Acute encephalitis presenting with symmetrical involvement of the bilateral basal ganglia].

    PubMed

    Arai, Hiromi; Goto, Tomohide; Kimura, Naoko; Miyama, Sahoko

    2013-11-01

    A 8-year-old girl was hospitalized with consciousness disturbance and involuntary movements five days after the onset of fever. Cranial MRI revealed symmetrical involvement of the bilateral basal ganglia with elevated ADC mapping, suggesting vasogenic edema.Her clinical symptoms improved with methylprednisolone pulse therapy without neurological sequelae. The rapid antigen test for group A beta-hemolytic streptococcus was positive and serum ASO was elevated. Myelin basic protein in cerebrospinal fluid was elevated. We suggest that the pathophysiological mechanism in the present case was not necrotic/cytotoxic but autoimmune inflammation, which is compatible with acute disseminated encephalomyelitis associated with streptococcal infection. PMID:24313006

  11. Unusual basal ganglia lesions in a diabetic uraemic patient proven to be demyelination: first pathological observation

    PubMed Central

    Tajima, Yasutaka; Mito, Yasunori; Yanai, Mituru; Fukazawa, Yu-ichiro

    2012-01-01

    A 64-year-old man suffering from diabetes mellitus and chronic renal failure was admitted to our hospital because of consciousness disturbance and parkinsonism. Cranial MRI showed very characteristic features involving the bilateral basal ganglia. Subsequent postmortem examinations demonstrated demyelination in the affected areas. These myelin destruction patterns were quite similar to those of central pontine myelinolysis. However, rapid correction of hyponatraemia was ruled out in this patient. Therefore, a new demyelinating brain disease associated with diabetes mellitus and chronic renal failure was suggested. PMID:22948993

  12. 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

  13. Usefulness of voxel-based lesion mapping for predicting motor recovery in subjects with basal ganglia hemorrhage

    PubMed Central

    Kim, Dae Hyun; Kyeong, Sunghyon; Cho, Yoona; Jung, Tae-min; Ahn, Sung Jun; Park, Yoon Ghil

    2016-01-01

    Abstract It is important to estimate motor recovery in the early phase after stroke. Many studies have demonstrated that both diffusion tensor tractography (DTT) and motor-evoked potentials (MEP) are valuable predictors of motor recovery, but these modalities do not directly reflect the status of the injured gray matter. We report on 2 subjects with basal ganglia hemorrhage who showed similar DTT and MEP findings, but had markedly different clinical outcomes. Specifically, Subject 1 showed no improvement in motor function, whereas Subject 2 exhibited substantial improvement 7 weeks after onset. To determine if differences in gray matter might lend insight into these different outcomes, we analyzed gray matter lesions of the 2 subjects using a novel voxel-based lesion mapping method. The lesion of Subject 1 mainly included the putamen, thalamus, and Heschl's gyri, indicating extension of the hemorrhage in the posterior direction. In contrast, the lesion of Subject 2 mainly included the putamen, insula, and pallidum, indicating that the hemorrhage extended anterior laterally. These differential findings suggest that voxel-based gray matter lesion mapping may help to predict differential motor recovery in subjects with basal ganglia hemorrhage with similar DTT and MEP findings. PMID:27281090

  14. [The role of the Basal Ganglia in Creating Receptive Fields in the Primary Auditory Cortex and Mechanisms of their Plasticity].

    PubMed

    Silkis, I G

    2015-01-01

    We suggest a mechanism for creating receptive fields of neurons in the primary auditory cortex (A1) and ventral part of the medial geniculate body (MGBv) in which the "direct" pathway through the basal ganglia participates. Dopamine released in the striatum in response to appearance of a sound tone promotes the induction of LTP of the efficacy of "strong" inputs and LTD of "weak" inputs from A1 to striatonigral cells due to activation of D1 receptors on these cells. Subsequent reorganization of neuronal activity in the network A1 field--basal ganglia--MGBv--A1 field results in a disinhibition of MGBv neuron activity, contrasting amplification of neural representation of a sound tone in MGBv and A1 field, and sharpening the receptive fields. Plastic shift of neuronal receptive fields is based on modification of efficacy of synaptic transmissions between the neocortex and striatum, and between all units of thalamocortical loop. Synaptic modification could be promoted by synchronization of activity of neurons which is based on the high-frequency oscillations relying on interdependent functioning of inhibitory cells in the considered loops. PMID:26506643

  15. Millisecond timescale disinhibition mediates fast information transmission through an avian basal ganglia loop

    PubMed Central

    Leblois, Arthur; Bodor, Ágnes L; Person, Abigail L; Perkel, David J

    2010-01-01

    Avian song learning shares striking similarities with human speech acquisition and requires a basal ganglia (BG)-thalamo-cortical circuit. Information processing and transmission speed in the BG is thought to be limited by synaptic architecture of two serial inhibitory connections. Propagation speed may be critical in the avian BG circuit given the temporally precise control of musculature during vocalization. We used electrical stimulation of the cortical inputs to the BG to study, with fine time resolution, the functional connectivity within this network. We found that neurons in thalamic and cortical nuclei that are not directly connected with the stimulated area can respond to the stimulation with extremely short latencies. Through pharmacological manipulations, we trace this property back to the BG, and show that the cortical stimulation triggers fast disinhibition of the thalamic neurons. Surprisingly, feedforward inhibition mediated by striatal inhibitory neurons onto BG output neurons sometimes precedes the monosynaptic excitatory drive from cortical afferents. The fast feedforward inhibition lengthens a single inter-spike interval in BG output neurons by just a few milliseconds. This short delay is sufficient to drive a strong, brief increase in firing probability in the target thalamic neurons, evoking short latency responses. By blocking glutamate receptors in vivo, we show that thalamic responses do not appear to rely on excitatory drive, and we show in a theoretical model that they could be mediated by post-inhibitory rebound properties. Such fast signalling through disinhibition and rebound may be a crucial specialization for learning of rapid and temporally precise motor acts such as vocal communication. PMID:20007467

  16. Millisecond timescale disinhibition mediates fast information transmission through an avian basal ganglia loop.

    PubMed

    Leblois, Arthur; Bodor, Agnes L; Person, Abigail L; Perkel, David J

    2009-12-01

    Avian song learning shares striking similarities with human speech acquisition and requires a basal ganglia (BG)-thalamo-cortical circuit. Information processing and transmission speed in the BG is thought to be limited by synaptic architecture of two serial inhibitory connections. Propagation speed may be critical in the avian BG circuit given the temporally precise control of musculature during vocalization. We used electrical stimulation of the cortical inputs to the BG to study, with fine time resolution, the functional connectivity within this network. We found that neurons in thalamic and cortical nuclei that are not directly connected with the stimulated area can respond to the stimulation with extremely short latencies. Through pharmacological manipulations, we trace this property back to the BG and show that the cortical stimulation triggers fast disinhibition of the thalamic neurons. Surprisingly, feedforward inhibition mediated by striatal inhibitory neurons onto BG output neurons sometimes precedes the monosynaptic excitatory drive from cortical afferents. The fast feedforward inhibition lengthens a single interspike interval in BG output neurons by just a few milliseconds. This short delay is sufficient to drive a strong, brief increase in firing probability in the target thalamic neurons, evoking short-latency responses. By blocking glutamate receptors in vivo, we show that thalamic responses do not appear to rely on excitatory drive, and we show in a theoretical model that they could be mediated by postinhibitory rebound properties. Such fast signaling through disinhibition and rebound may be a crucial specialization for learning of rapid and temporally precise motor acts such as vocal communication. PMID:20007467

  17. A spiking Basal Ganglia model of synchrony, exploration and decision making

    PubMed Central

    Mandali, Alekhya; Rengaswamy, Maithreye; Chakravarthy, V. Srinivasa; Moustafa, Ahmed A.

    2015-01-01

    To make an optimal decision we need to weigh all the available options, compare them with the current goal, and choose the most rewarding one. Depending on the situation an optimal decision could be to either “explore” or “exploit” or “not to take any action” for which the Basal Ganglia (BG) is considered to be a key neural substrate. In an attempt to expand this classical picture of BG function, we had earlier hypothesized that the Indirect Pathway (IP) of the BG could be the subcortical substrate for exploration. In this study we build a spiking network model to relate exploration to synchrony levels in the BG (which are a neural marker for tremor in Parkinson's disease). Key BG nuclei such as the Sub Thalamic Nucleus (STN), Globus Pallidus externus (GPe) and Globus Pallidus internus (GPi) were modeled as Izhikevich spiking neurons whereas the Striatal output was modeled as Poisson spikes. The model is cast in reinforcement learning framework with the dopamine signal representing reward prediction error. We apply the model to two decision making tasks: a binary action selection task (similar to one used by Humphries et al., 2006) and an n-armed bandit task (Bourdaud et al., 2008). The model shows that exploration levels could be controlled by STN's lateral connection strength which also influenced the synchrony levels in the STN-GPe circuit. An increase in STN's lateral strength led to a decrease in exploration which can be thought as the possible explanation for reduced exploratory levels in Parkinson's patients. Our simulations also show that on complete removal of IP, the model exhibits only Go and No-Go behaviors, thereby demonstrating the crucial role of IP in exploration. Our model provides a unified account for synchronization, action section, and explorative behavior. PMID:26074761

  18. Motor thalamus integration of cortical, cerebellar and basal ganglia information: implications for normal and parkinsonian conditions.

    PubMed

    Bosch-Bouju, Clémentine; Hyland, Brian I; Parr-Brownlie, Louise C

    2013-01-01

    Motor thalamus (Mthal) is implicated in the control of movement because it is strategically located between motor areas of the cerebral cortex and motor-related subcortical structures, such as the cerebellum and basal ganglia (BG). The role of BG and cerebellum in motor control has been extensively studied but how Mthal processes inputs from these two networks is unclear. Specifically, there is considerable debate about the role of BG inputs on Mthal activity. This review summarizes anatomical and physiological knowledge of the Mthal and its afferents and reviews current theories of Mthal function by discussing the impact of cortical, BG and cerebellar inputs on Mthal activity. One view is that Mthal activity in BG and cerebellar-receiving territories is primarily "driven" by glutamatergic inputs from the cortex or cerebellum, respectively, whereas BG inputs are modulatory and do not strongly determine Mthal activity. This theory is steeped in the assumption that the Mthal processes information in the same way as sensory thalamus, through interactions of modulatory inputs with a single driver input. Another view, from BG models, is that BG exert primary control on the BG-receiving Mthal so it effectively relays information from BG to cortex. We propose a new "super-integrator" theory where each Mthal territory processes multiple driver or driver-like inputs (cortex and BG, cortex and cerebellum), which are the result of considerable integrative processing. Thus, BG and cerebellar Mthal territories assimilate motivational and proprioceptive motor information previously integrated in cortico-BG and cortico-cerebellar networks, respectively, to develop sophisticated motor signals that are transmitted in parallel pathways to cortical areas for optimal generation of motor programmes. Finally, we briefly review the pathophysiological changes that occur in the BG in parkinsonism and generate testable hypotheses about how these may affect processing of inputs in the Mthal

  19. Cortico-basal ganglia circuits involved in different motivation disorders in non-human primates.

    PubMed

    Sgambato-Faure, Véronique; Worbe, Yulia; Epinat, Justine; Féger, Jean; Tremblay, Léon

    2016-01-01

    The ventral striatum (VS) is of particular interest in the study of neuropsychiatric disorders. In this study, performed on non-human primates, we associated local perturbation with monosynaptic axonal tracer injection into medial, central and lateral VS to characterize anatomo-functional circuits underlying the respective expression of sexual manifestations, stereotyped behaviors and hypoactive state associated with loss of food motivation. For the three behavioral effects, we demonstrated the existence of three distinct cortico-basal ganglia (BG) circuits that were topographically organized and overlapping at some cortical (orbitofrontal cortex, anterior cingulate cortex) and subcortical (caudal levels of BG) levels, suggesting interactions between motivation domains. Briefly, erection was associated with a circuit involving the orbitofrontal cortex, medial prefrontal cortex (areas 10, 11) and limbic parts of BG, i.e. medial parts of the pallidal complex and the substantia nigra pars reticulata (SNr). Stereotyped behavior was linked to a circuit involving the lateral orbitofrontal cortex (area 12/47) and limbic parts of the pallidal complex and of the SNr, while the apathetic state was underlined by a circuit involving not only the orbital and medial prefrontal cortex but also the lateral prefrontal cortex (area 8, 45), the anterior insula and the lateral parts of the medial pallidal complex and of the ventro-medial SNr. For the three behavioral effects, the cortico-BG circuits mainly involved limbic regions of the external and internal pallidum, as well as the limbic part of the substantia nigra pars reticulata (SNr), suggesting the involvement of both direct and indirect striatal pathways and both output BG structures. As these motivation disorders could still be induced in dopamine (DA)-depleted monkeys, we suggest that DA issued from the substantia nigra pars compacta (SNc) modulates their expression rather than causes them. Finally, this study may give some

  20. The basal ganglia cholinergic neurochemistry of progressive supranuclear palsy and other neurodegenerative diseases

    PubMed Central

    Warren, N M; Piggott, M A; Lees, A J; Burn, D J

    2007-01-01

    Background Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder involving motor and cognitive dysfunction. Currently, there is no effective treatment either for symptomatic relief or disease modification. This relates, in part, to a lack of knowledge of the underlying neurochemical abnormalities, including cholinergic receptor status in the basal ganglia. Aim To measure muscarinic M2 and M4 receptors in the basal ganglia in PSP. Methods The muscarinic M2 (presynaptic) and M4 (postsynaptic) receptors in the striatum, pallidum and adjacent insular cortex were autoradiographically measured in pathologically confirmed cases of PSP (n = 18), and compared with cases of Lewy body dementias (LBDs; n = 45), Alzheimer's disease (AD; n = 39) and controls (n = 50). Results In cases of PSP, there was a reduction in M2 and M4 receptors in the posterior caudate and putamen compared to controls, but no significant changes in the pallidum. Cases with AD showed lower M2 receptors in the posterior striatum. Groups with LBD and AD showed higher M2 binding in the insular cortex compared with controls. Conclusions The results suggest loss of posterior striatal cholinergic interneurones in PSP, and reduction in medium spiny projection neurones bearing M4 receptors. These results should be taken in the context of more widespread pathology in PSP, but may have implications for future trials of cholinergic treatments. PMID:17178818

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

    PubMed

    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

  2. Role of the indirect pathway of the basal ganglia in perceptual decision making.

    PubMed

    Wei, Wei; Rubin, Jonathan E; Wang, Xiao-Jing

    2015-03-01

    The basal ganglia (BG) play an important role in motor control, reinforcement learning, and perceptual decision making. Modeling and experimental evidence suggest that, in a speed-accuracy tradeoff, the corticostriatal pathway can adaptively adjust a decision threshold (the amount of information needed to make a choice). In this study, we go beyond the focus of previous works on the direct and hyperdirect pathways to examine the contribution of the indirect pathway of the BG system to decision making in a biophysically based spiking network model. We find that the mechanism of adjusting the decision threshold by plasticity of the corticostriatal connections is effective, provided that the indirect pathway counterbalances the direct pathway in their projections to the output nucleus. Furthermore, in our model, changes within basal ganglia connections similar to those that arise in parkinsonism give rise to strong beta oscillations. Specifically, beta oscillations are produced by an abnormal enhancement of the interactions between the subthalamic nucleus (STN) and the external segment of globus pallidus (GPe) in the indirect pathway, with an oscillation frequency that depends on the excitatory cortical input to the STN and the inhibitory input to the GPe from the striatum. In a parkinsonian state characterized by pronounced beta oscillations, the mean reaction time and range of threshold variation (a measure of behavioral flexibility) are significantly reduced compared with the normal state. Our work thus reveals a specific circuit mechanism for impairments of perceptual decision making associated with Parkinson's disease. PMID:25740532

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

    SciTech Connect

    Palacios, J.M.; Chinaglia, G.; Rigo, M.; Ulrich, J.; Probst, A. )

    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 control 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.

  4. Role of the Indirect Pathway of the Basal Ganglia in Perceptual Decision Making

    PubMed Central

    Wei, Wei; Rubin, Jonathan E.

    2015-01-01

    The basal ganglia (BG) play an important role in motor control, reinforcement learning, and perceptual decision making. Modeling and experimental evidence suggest that, in a speed–accuracy tradeoff, the corticostriatal pathway can adaptively adjust a decision threshold (the amount of information needed to make a choice). In this study, we go beyond the focus of previous works on the direct and hyperdirect pathways to examine the contribution of the indirect pathway of the BG system to decision making in a biophysically based spiking network model. We find that the mechanism of adjusting the decision threshold by plasticity of the corticostriatal connections is effective, provided that the indirect pathway counterbalances the direct pathway in their projections to the output nucleus. Furthermore, in our model, changes within basal ganglia connections similar to those that arise in parkinsonism give rise to strong beta oscillations. Specifically, beta oscillations are produced by an abnormal enhancement of the interactions between the subthalamic nucleus (STN) and the external segment of globus pallidus (GPe) in the indirect pathway, with an oscillation frequency that depends on the excitatory cortical input to the STN and the inhibitory input to the GPe from the striatum. In a parkinsonian state characterized by pronounced beta oscillations, the mean reaction time and range of threshold variation (a measure of behavioral flexibility) are significantly reduced compared with the normal state. Our work thus reveals a specific circuit mechanism for impairments of perceptual decision making associated with Parkinson's disease. PMID:25740532

  5. The basal ganglia and rule-governed language use: evidence from vascular and degenerative conditions.

    PubMed

    Longworth, C E; Keenan, S E; Barker, R A; Marslen-Wilson, W D; Tyler, L K

    2005-03-01

    The Declarative/Procedural Model of Pinker, Ullman and colleagues claims that the basal ganglia are part of a fronto-striatal procedural memory system which applies grammatical rules to combine morphemes (the smallest meaningful units in language) into complex words (e.g. talk-ed, talk-ing). We tested this claim by investigating whether striatal damage or loss of its dopaminergic innervation is reliably associated with selective regular past tense deficits in patients with subcortical cerebrovascular damage, Parkinson's disease or Huntington's disease. We focused on past tense morphology since this allows us to contrast the regular past tense (jump-jumped), which is rule-based, with the irregular past tense (sleep-slept), which is not. We used elicitation and priming tasks to test patients' ability to comprehend and produce inflected forms. We found no evidence of a consistent association between striatal dysfunction and selective impairment of regular past tense morphology, suggesting that the basal ganglia are not essential for processing the regular past tense as a sequence of morphemes, either in comprehension or production, in contrast to the claims of the Declarative/Procedural Model. All patient groups showed normal activation of semantic and morphological representations in comprehension, despite difficulties suppressing semantically appropriate alternatives when trying to inflect novel verbs. This is consistent with previous reports that striatal dysfunction spares automatic activation of linguistic information, but disrupts later language processes that require inhibition of competing alternatives. PMID:15659423

  6. An Interactive Channel Model of the Basal Ganglia: Bifurcation Analysis Under Healthy and Parkinsonian Conditions

    PubMed Central

    2013-01-01

    Oscillations in the basal ganglia are an active area of research and have been shown to relate to the hypokinetic motor symptoms of Parkinson’s disease. We study oscillations in a multi-channel mean field model, where each channel consists of an interconnected pair of subthalamic nucleus and globus pallidus sub-populations. To study how the channels interact, we perform two-dimensional bifurcation analysis of a model of an individual channel, which reveals the critical boundaries in parameter space that separate different dynamical modes; these modes include steady-state, oscillatory, and bi-stable behaviour. Without self-excitation in the subthalamic nucleus a single channel cannot generate oscillations, yet there is little experimental evidence for such self-excitation. Our results show that the interactive channel model with coupling via pallidal sub-populations demonstrates robust oscillatory behaviour without subthalamic self-excitation, provided the coupling is sufficiently strong. We study the model under healthy and Parkinsonian conditions and demonstrate that it exhibits oscillations for a much wider range of parameters in the Parkinsonian case. In the discussion, we show how our results compare with experimental findings and discuss their possible physiological interpretation. For example, experiments have found that increased lateral coupling in the rat basal ganglia is correlated with oscillations under Parkinsonian conditions. PMID:23945348

  7. [Bilateral lesions of the basal ganglia as a sign of chronic carbon monoxide intoxication].

    PubMed

    Haaxma, C A; van Eijk, J J J; van der Vilet, A M; Renier, W O; Bloem, B R

    2007-04-14

    A 40-year-old, previously healthy man presented with a subacute coordination disorder and intermittent paraesthesias of the right arm that had begun several months before and had disappeared spontaneously within a few weeks. Neurological examination showed a mildly flattened nasolabial fold on the right side and subtle hypertonia of the right arm. A CT-scan of the brain revealed calcifications in the left caudate nucleus and putamen. Cerebral MRI showed markedly enlarged Virchow-Robin spaces bilaterally in the basal ganglia and extensive periventricular white matter lesions. The differential diagnosis of these radiological findings included carbon monoxide intoxication. Ancillary investigations excluded other causes for the radiological abnormalities, and a defective gas stove that produced carbon monoxide was found in the patient's house. Although carbon monoxide poisoning is relatively rare in the Netherlands, it remains important to be alert to the possibility of such exposure. Radiological findings, notably bilateral lesions of the basal ganglia, may point in the direction of the proper diagnosis. PMID:17472119

  8. A case of vitamin B12 deficiency with involuntary movements and bilateral basal ganglia lesions.

    PubMed

    Kitamura, Taisuke; Gotoh, Seiji; Takaki, Hayato; Kiyuna, Fumi; Yoshimura, Sohei; Fujii, Kenichiro

    2016-07-28

    An 86-year-old woman with a one-year history of dementia was admitted to our hospital complaining of loss of appetite, hallucinations, and disturbance of consciousness. She gradually presented with chorea-like involuntary movements of the extremities. Diffusion-weighted magnetic resonance imaging (MRI) showed bilateral symmetrical hyperintense signals in the basal ganglia. The serum vitamin B12 level was below the lower detection limit of 50 pg/ml. The homocysteine level was markedly elevated at 115.8 nmol/ml. Anti-intrinsic factor and anti-parietal cell antibody tests were positive. Gastrointestinal endoscopy revealed atrophic gastritis. The patient was diagnosed with encephalopathy due to vitamin B12 deficiency caused by pernicious anemia. Involuntary movements and MRI abnormalities improved with parenteral vitamin B12 supplementation. Bilateral basal ganglia lesions are rare manifestations of adult vitamin B12 deficiency. The present case is considered valuable in identifying the pathophysiology of involuntary movement due to vitamin B12 deficiency. PMID:27356735

  9. Germinoma originating in the basal ganglia and thalamus: MR and CT evaluation

    SciTech Connect

    Shuichi Higano; Shoki Takahashi; Kiyoshi Ishii

    1994-09-01

    Purpose: to describe MR and CT features of germinoma originating in the basal ganglia and thalamus and to discuss the roles of each modality for its diagnosis. Methods: MR and CT studies of six cases of germinomas, five of which were histologically proved, were retrospectively reviewed. T1-weighted, T2-weighted, and contrast-enhanced T1-weighted conventional spin-echo images, and unenhanced and contrast-enhanced CT images were evaluated. Results: Typically, the tumor consisted of an irregular solid area with contrast enhancement and various-size cysts. Cystic components were found in five cases and calcification in four. Intratumoral hemorrhage was noted in one. Ipsilateral cerebral hemiatrophy and brain stem hemiatrophy were noted in three cases each. MR was superior to CT in evaluating precise tumor extension, cystic components, and intratumoral hemorrhage, although in one case, extension of the tumor was better defined on CT in its early stage. Calcification was difficult to identify by MR alone. The solid components of the tumors generally showed slightly high density on CT, which seemed to be characteristic compared with nonspecific intensity pattern on MR. Conclusion: The combination of CT and MR findings allows early detection and appropriate diagnosis of the mass in the basal ganglia and/or thalamus. 26 refs., 4 figs., 1 tab.

  10. 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

  11. The role of the basal ganglia in the control of automatic visuospatial attention.

    PubMed

    Fielding, Joanne; Georgiou-Karistianis, Nellie; White, Owen

    2006-09-01

    Cognitive impairments in patients with basal ganglia dysfunction are primarily revealed where performance relies on internal, voluntary control processes. Evidence suggests that this also extends to impaired control of more automatic processes, including visuospatial attention. The present study used a non-predictive peripheral cueing paradigm to compare and contrast visuospatial deficits in patients with Parkinson's disease (PD) with those previously revealed in patients with Huntington's disease (HD) (Fielding et al., 2006a). Compared to age-matched controls, both PD and HD patients exhibited increased distractibility or poor fixation, however only PD patients responded erroneously to cue stimuli more frequently than control subjects. All subjects demonstrated initial facilitation for valid versus invalid cues following the shorter stimulus-onset asynchronies (SOAs) and a performance decrement at the longer SOAs (inhibition of return), although there was a clear differentiation between these groups for immediate SOAs. Unlike both control and PD subjects, where IOR manifested between 350 and 1000 msec, IOR was evident as early as 150 msec for HD patients. Further, for PD patients, spatially valid cues resulted in hyper-reflexivity following 150 msec SOAs, with saccadic latencies shorter than those generated in response to un-cued targets. Thus contrasting deficits were revealed in PD and HD, emphasizing the important contribution of the basal ganglia in the control of more automatic behaviors PMID:16961947

  12. Modeling effects of cerebellar and basal ganglia lesions on adaptation and anticipation during sensorimotor synchronization.

    PubMed

    van der Steen, M C Marieke; Schwartze, Michael; Kotz, Sonja A; Keller, Peter E

    2015-03-01

    This study addressed the role of subcortical brain structures in temporal adaptation and anticipation during sensorimotor synchronization. The performance of patients with cerebellar or basal ganglia lesions was compared with that of healthy control participants on tasks requiring the synchronization of drum strokes with adaptive and tempo-changing auditory pacing sequences. The precision of sensorimotor synchronization was generally lower in patients relative to controls (i.e., variability of asynchronies was higher in patients), although synchronization accuracy (mean asynchrony) was commensurate. A computational model of adaptation and anticipation (ADAM) was used to examine potential sources of individual differences in precision by estimating participants' use of error correction, temporal prediction, and the amount of variability associated with central timekeeping and peripheral motor processes. Parameter estimates based on ADAM indicate that impaired precision was attributable to increased variability of timekeeper and motor processes as well as to reduced temporal prediction in both patient groups. Adaptive processes related to continuously applied error correction were, by contrast, intact in patients. These findings highlight the importance of investigating how subcortical structures, including the cerebellum and basal ganglia, interact with a broader network of cortical regions to support temporal adaptation and anticipation during sensorimotor synchronization. PMID:25773623

  13. Microstructural Changes within the Basal Ganglia Differ between Parkinson Disease Subtypes

    PubMed Central

    Nagae, Lidia M.; Honce, Justin M.; Tanabe, Jody; Shelton, Erika; Sillau, Stefan H.; Berman, Brian D.

    2016-01-01

    Diffusion tensor imaging (DTI) of the substantia nigra has shown promise in detecting and quantifying neurodegeneration in Parkinson disease (PD). It remains unknown, however, whether differences in microstructural changes within the basal ganglia underlie PD motor subtypes. We investigated microstructural changes within the basal ganglia of mild to moderately affected PD patients using DTI and sought to determine if microstructural changes differ between the tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtypes. Fractional anisotropy, mean diffusivity, radial, and axial diffusivity were obtained from bilateral caudate, putamen, globus pallidus, and substantia nigra of 21 PD patients (12 TD and 9 PIGD) and 20 age-matched healthy controls. T-tests and ANOVA methods were used to compare PD patients, subtypes, and controls, and Spearman correlations tested for relationships between DTI and clinical measures. We found our cohort of PD patients had reduced fractional anisotropy within the substantia nigra and increased mean and radial diffusivity within the substantia nigra and globus pallidus compared to controls, and that changes within those structures were largely driven by the PIGD subtype. Across all PD patients fractional anisotropy within the substantia nigra correlated with disease stage, while in PIGD patients increased diffusivity within the globus pallidus correlated with disease stage and motor severity. We conclude that PIGD patients have more severely affected microstructural changes within the substantia nigra compared to TD, and that microstructural changes within the globus pallidus may be particularly relevant for the manifestation of the PIGD subtype. PMID:26941615

  14. [Gait disturbances related to dysfunction of the cerebral cortex and basal ganglia].

    PubMed

    Takezawa, Nobuo; Mizuno, Toshiki; Seo, Kazuya; Kondo, Masaki; Nakagawa, Masanori

    2010-11-01

    This review aimed to characterize the gait disturbances in Parkinson disease (PD) and highlight how a rehabilitation program would affect the care of patients with PD. The typical PD gait is a type of hypokinetic gait characterized by reduced stride length and velocity; shortening of the swing phase; and increase in the stance phase, double-limb support duration, and cadence rate. In the advanced phase of PD, start hesitation, shuffling and festinating gait, propulsion, and freezing of gait (FOG) become remarkable. Notably, in PD, attention may influence gait control, and sensory cueing may improve the stride length. Our study on gait impairment in PD by using a three-dimensional motion analysis system revealed that the stride length and walking speed decreased, but there was no change in cadence. The decreased stride length was due to reduction in the range of movement at the leg and pelvic joints. A 4-week physical rehabilitation program for PD improved the stride length and walking speed;this was achieved by increasing the range of movement of at the leg and pelvic joints. We also assessed the effects of a rehabilitation program for patients with PD who experienced FOG. Although the lower limb function was more impaired in patients with PD and FOG than in those with PD without FOG, the rehabilitation program was effective even for patients with PD and FOG. FOG might be associated with functional impairment of the lower limb as well as dysfunction of the fronto-basal ganglia circuit. We also reported 3 cases of camptocormia (bent spine syndrome) with autonomic dysfunction and rapid eye movement (REM) sleep behavior disorders (RBD) and compared their symptoms with those reported elsewhere. We think that the pedunculopontine nuclear area may control the postural muscle tone and locomotion in PD. On the basis of the results of our rehabilitation programs, we speculate that physical modalities may modify synaptic plasticity by utilizing the cerebellar and/or afferent

  15. MRI Findings of Syndrome of Acute Bilateral Symmetrical Basal Ganglia Lesions in Diabetic Uremia: A Case Report and Literature Review

    PubMed Central

    Cao, Xin; Fang, Qiang

    2016-01-01

    The syndrome of acute bilateral basal ganglia lesions is an uncommon clinical occurrence exhibiting acute onset of movement abnormalities, which can be seen almost exclusively among patients with chronic renal failure, especially in the setting of concurrent diabetes mellitus. Symmetrical lesions located in basal ganglia demonstrated in MRI are typical manifestation of this syndrome. Our study includes routine MRI examination, MRS, 3D-ASL, and SWI findings, which have been rarely reported and will contribute to diagnosing more cases about this syndrome. PMID:27493824

  16. Basal ganglia lesions and psychological analyses of the control of voluntary movement.

    PubMed

    Wing, A M; Miller, E

    1984-01-01

    Psychological accounts of the voluntary control of movement recognize the contribution of perceptual and decision processes as well as processes such as motor memory and timing that are more obviously a part of motor control. A model including these and other components is outlined in relation to tracking, a task that has often been used to study human perceptual-motor performance. The need for experimental control in addressing such multi-process models is emphasized. A number of studies of perceptual-motor performance deficits in patients with Parkinson's disease are reviewed. The methods by which the studies relate the behavioural data to the hypothesized underlying processes may be broadly grouped according to whether they use a subtractive logic or take a decompositional approach. These studies suggest that the basal ganglia play a role in the activation of pre-planned movement. PMID:6568151

  17. 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

  18. 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

  19. Limb apraxia in patients with damage confined to the left basal ganglia and thalamus.

    PubMed Central

    De Renzi, E; Faglioni, P; Scarpa, M; Crisi, G

    1986-01-01

    Limb apraxia was investigated with standardised tests in 14 patients whose CT scan provided evidence of a vascular lesion confined to the left basal ganglia, or the thalamus, or both, and not involving the cortex or adjacent white matter. Five patients were severely impaired in imitating movements and pantomiming object use. Four of them also performed poorly when tested with real objects. In two patients the lesion was primarily thalamic and in three the lesion was primarily in the lenticular nucleus and the posterior limb of the internal capsule. Patients without apraxia generally had smaller injuries, but there were exceptions. Apraxia is currently conceived of as due to damage of cortical areas and their cortico-cortical connections, but the present data suggest that the model should be enlarged to include the deep nuclei and the pathways running through them. Images PMID:3760891

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

    PubMed

    Ikemoto, Satoshi; Yang, Chen; Tan, Aaron

    2015-09-01

    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

  1. Movement disorders in astrocytomas of the basal ganglia and the thalamus.

    PubMed Central

    Krauss, J K; Nobbe, F; Wakhloo, A K; Mohadjer, M; Vach, W; Mundinger, F

    1992-01-01

    In a series of 225 patients with astrocytomas (grades I-IV) of the basal ganglia and the thalamus, 20 had a movement disorder. In all patients the histological diagnosis was verified by stereotactic biopsy. Tremor was observed in twelve patients, dystonia in eight, chorea in three, and chorea/ballismus and myoclonus in one. The tumour involved the thalamus in 16 patients. Corticospinal tract dysfunction was evident in 70% of the patients with movement disorders and in 73% of those without. Demographic, clinical, histological and neuroradiological data of the patients with a movement disorder were compared with the data of patients without. CT data yielded no differences with respect to the involvement of anatomical structures. Movement disorders were significantly associated with low-grade astrocytomas. Images PMID:1479396

  2. Identifying the Basal Ganglia Network Model Markers for Medication-Induced Impulsivity in Parkinson's Disease Patients

    PubMed Central

    Balasubramani, Pragathi Priyadharsini; Chakravarthy, V. Srinivasa; Ali, Manal; Ravindran, Balaraman; Moustafa, Ahmed A.

    2015-01-01

    Impulsivity, i.e. irresistibility in the execution of actions, may be prominent in Parkinson's disease (PD) patients who are treated with dopamine precursors or dopamine receptor agonists. In this study, we combine clinical investigations with computational modeling to explore whether impulsivity in PD patients on medication may arise as a result of abnormalities in risk, reward and punishment learning. In order to empirically assess learning outcomes involving risk, reward and punishment, four subject groups were examined: healthy controls, ON medication PD patients with impulse control disorder (PD-ON ICD) or without ICD (PD-ON non-ICD), and OFF medication PD patients (PD-OFF). A neural network model of the Basal Ganglia (BG) that has the capacity to predict the dysfunction of both the dopaminergic (DA) and the serotonergic (5HT) neuromodulator systems was developed and used to facilitate the interpretation of experimental results. In the model, the BG action selection dynamics were mimicked using a utility function based decision making framework, with DA controlling reward prediction and 5HT controlling punishment and risk predictions. The striatal model included three pools of Medium Spiny Neurons (MSNs), with D1 receptor (R) alone, D2R alone and co-expressing D1R-D2R. Empirical studies showed that reward optimality was increased in PD-ON ICD patients while punishment optimality was increased in PD-OFF patients. Empirical studies also revealed that PD-ON ICD subjects had lower reaction times (RT) compared to that of the PD-ON non-ICD patients. Computational modeling suggested that PD-OFF patients have higher punishment sensitivity, while healthy controls showed comparatively higher risk sensitivity. A significant decrease in sensitivity to punishment and risk was crucial for explaining behavioral changes observed in PD-ON ICD patients. Our results highlight the power of computational modelling for identifying neuronal circuitry implicated in learning, and its

  3. Auditory tuning for spatial cues in the barn owl basal ganglia.

    PubMed

    Cohen, Y E; Knudsen, E I

    1994-07-01

    1. The basal ganglia are known to contribute to spatially guided behavior. In this study, we investigated the auditory response properties of neurons in the barn owl paleostriatum augmentum (PA), the homologue of the mammalian striatum. The data suggest that the barn owl PA is specialized to process spatial cues and, like the mammalian striatum, is involved in spatial behavior. 2. Single- and multiunit sites were recorded extracellularly in ketamine-anesthetized owls. Spatial receptive fields were measured with a free-field sound source, and tuning for frequency and interaural differences in timing (ITD) and level (ILD) was assessed using digitally synthesized dichotic stimuli. 3. Spatial receptive fields measured at nine multiunit sites were tuned to restricted regions of space: tuning widths at half-maximum response averaged 22 +/- 9.6 degrees (mean +/- SD) in azimuth and 54 +/- 22 degrees in elevation. 4. PA sites responded strongly to broadband sounds. When frequency tuning could be measured (n = 145/201 sites), tuning was broad, averaging 2.7 kHz at half-maximum response, and tended to be centered near the high end of the owl's audible range. The mean best frequency was 6.2 kHz. 5. All PA sites (n = 201) were selective for both ITD and ILD. ITD tuning curves typically exhibited a single, large "primary" peak and often smaller, "secondary" peaks at ITDs ipsilateral and/or contralateral to the primary peak. Three indices quantified the selectivity of PA sites for ITD. The first index, which was the percent difference between the minimum and maximum response as a function of ITD, averaged 100 +/- 29%. The second index, which represented the size of the largest secondary peak relative to that of the primary peak, averaged 49 +/- 23%. The third index, which was the width of the primary ITD peak at half-maximum response, averaged only 66 +/- 35 microseconds. 6. The majority (96%; n = 192/201) of PA sites were tuned to a single "best" value of ILD. The widths of ILD

  4. Extrastriatal D2-like receptors modulate basal ganglia pathways in normal and parkinsonian monkeys

    PubMed Central

    Rommelfanger, Karen S.; Masilamoni, Gunasingh J.; Smith, Yoland; Wichmann, Thomas

    2012-01-01

    According to traditional models of the basal ganglia-thalamocortical network of connections, dopamine exerts D2-like receptor (D2LR)-mediated effects through actions on striatal neurons that give rise to the “indirect” pathway, secondarily affecting the activity in the internal and external pallidal segments (GPi and GPe, respectively) and the substantia nigra pars reticulata (SNr). However, accumulating evidence from the rodent literature suggests that D2LR activation also directly influences synaptic transmission in these nuclei. To further examine this issue in primates, we combined in vivo electrophysiological recordings and local intracerebral microinjections of drugs with electron microscopic immunocytochemistry to study D2LR-mediated modulation of neuronal activities in GPe, GPi, and SNr of normal and MPTP-treated (parkinsonian) monkeys. D2LR activation with quinpirole increased firing in most GPe neurons, likely due to a reduction of striatopallidal GABAergic inputs. In contrast, local application of quinpirole reduced firing in GPi and SNr, possibly through D2LR-mediated effects on glutamatergic inputs. Injections of the D2LR antagonist sulpiride resulted in effects opposite to those of quinpirole in GPe and GPi. D2 receptor immunoreactivity was most prevalent in putative striatal-like GABAergic terminals and unmyelinated axons in GPe, GPi, and SNr, but a significant proportion of immunoreactive boutons also displayed ultrastructural features of glutamatergic terminals. Postsynaptic labeling was minimal in all nuclei. The D2LR-mediated effects and pattern of distribution of D2 receptor immunoreactivity were maintained in the parkinsonian state. Thus, in addition to their preferential effects on indirect pathway striatal neurons, extrastriatal D2LR activation in GPi and SNr also influences direct pathway elements in the primate basal ganglia under normal and parkinsonian conditions. PMID:22131382

  5. Beta Frequency Synchronization in Basal Ganglia Output during Rest and Walk in a Hemiparkinsonian Rat

    PubMed Central

    Avila, Irene; Parr-Brownlie, Louise C.; Brazhnik, Elena; Castañeda, Edward; Bergstrom, Debra A.; Walters, J. R.

    2012-01-01

    Synchronized oscillatory neuronal activity in the beta frequency range has been observed in the basal ganglia of Parkinson’s disease patients and hypothesized to be antikinetic. The unilaterally lesioned rat model of Parkinson’s disease allows examination of this hypothesis by direct comparison of beta activity in basal ganglia output in non-lesioned and dopamine cell lesioned hemispheres during motor activity. Bilateral substantia nigra pars reticulata (SNpr) recordings of units and local field potentials (LFP) were obtained with EMG activity from the scapularis muscle in control and unilaterally nigrostriatal lesioned rats trained to walk on a rotary treadmill. After left hemispheric lesion, rats had difficulty walking contraversive on the treadmill but could walk in the ipsiversive direction. During inattentive rest, SNpr LFP power in the 12–25 Hz range (low beta) was significantly greater in the dopamine-depleted hemisphere than in non-lesioned and control hemispheres. During walking, low beta power was reduced in all hemispheres, while 25–40 Hz (high beta) activity was selectively increased in the lesioned hemisphere. High beta power increases were reduced by L-DOPA administration. SNpr spiking was significantly more synchronized with SNpr low beta LFP oscillations during rest and high beta LFP oscillations during walking in the dopamine-depleted hemispheres compared with non-lesioned hemispheres. Data show that dopamine loss is associated with opposing changes in low and high beta range SNpr activity during rest and walk and suggest that increased synchronization of high beta activity in SNpr output from the lesioned hemisphere during walking may contribute to gait impairment in the hemiparkinsonian rat. PMID:19948166

  6. Brain Atrophy Correlates with Severe Enlarged Perivascular Spaces in Basal Ganglia among Lacunar Stroke Patients

    PubMed Central

    Zhang, Xiaoyu; Ding, Lingling; Yang, Lei; Qin, Wei; Yuan, Junliang; Li, Shujuan; Hu, Wenli

    2016-01-01

    Background Enlarged perivascular spaces (EPVS) correlate with cognitive impairment and incident dementia. However, etiologies for severe basal ganglia EPVS (BG-EPVS) are still unclear. Our aim was to investigate the independent risk factors for severe BG-EPVS in patients with acute lacunar stroke. Methods We prospectively identified patients with lacunar stroke (diameter on DWI ≤ 20mm) from Jan 2011 to May 2015. Patients with severe BG-EPVS were identified on T2 weighted MRI. Age (± 1 year) and sex matched controls were also recruited in the same population (two controls for one case). Vascular risk factors, clinical data, EPVS in centrum semiovale (rated 0 to 4), white matter hyperintensities (WMH) (by Fazekas scale), brain atrophy (rated 0 to 6) were compared between two groups. Logistic regression was performed to determine independent risk factors for severe BG-EPVS. Results During study period, 89 patients with severe BG-EPVS and 178 matched controls were included. Vascular risk factors did not differ between two groups. Patients with severe BG-EPVS had lower level of HbA1c and diastolic BP at admission, but presented with larger infarct size, more severe WMH (including total WMH, periventricular WMH and deep WMH) and brain atrophy. In logistic regression, brain atrophy (OR = 1.40; 95%CI 1.13, 1.73) and deep WMH (OR = 1.88; 95%CI 1.24, 2.83) were independent risk factors for severe BG-EPVS. Conclusions Brain atrophy and deep WMH are independent risk factors for severe BG-EPVS, supporting the hypothesis that brain atrophy may be associated with the development of EPVS in basal ganglia. PMID:26900696

  7. The behavioural and motor consequences of focal lesions of the basal ganglia in man.

    PubMed

    Bhatia, K P; Marsden, C D

    1994-08-01

    The behavioural and movement disorders reported in 240 patients described in the literature with lesions affecting the caudate nucleus, putamen and the globus pallidus (lentiform nucleus) have been analysed. Reports were classified into two groups: small or isolated lesions involving the said nuclei alone; and large lesions with additional involvement of the adjacent internal capsule and/or periventricular white matter. Amongst the 240 cases, dystonia was the most frequent movement disorder recorded (36%); chorea (8%) and parkinsonism (6%) or dystonia-parkinsonism (3%) were uncommon. The commonest behavioural disturbance was the syndrome of abulia (apathy with loss of initiative and of spontaneous thought and emotional responses) (13%); disinhibition was rare (4%). Confusion usually was associated with intracerebral haemorrhage and depression was a relatively non-specific finding. Aphasia was extremely rare with lesions confined to these basal ganglia structures. Lesions of the caudate nucleus rarely caused motor disorders but were more likely to cause behavioural problems. Chorea has been described in only 6% of those with caudate lesions, and dystonia in only 9%. The most significant behavioural disturbance described in 28% of those with caudate lesions was the syndrome of abulia, sometimes alternating with disinhibition (11%). Lesions of the lentiform nuclei rarely caused abulia (10%) and did not produce disinhibition, but they commonly caused dystonia (49%), particularly when the putamen was involved (63%). Bilateral lesions of the lentiform nuclei, either of the globus pallidus or of the putamen, caused parkinsonism (19%) or dystonia-parkinsonism (6%) infrequently. The prominence of the behavioural disturbance of abulia with caudate lesions emphasizes the more complex cognitive role of this basal ganglia structure. The frequent occurrence of dystonia and less commonly of parkinsonism with lentiform lesions emphasize the motor roles of putamen and globus

  8. Region of interest template for the human basal ganglia: comparing EPI and standardized space approaches.

    PubMed

    Prodoehl, Janey; Yu, Hong; Little, Deborah M; Abraham, Ivy; Vaillancourt, David E

    2008-02-01

    Identifying task-related activation in the basal ganglia (BG) is an important area of interest in normal motor systems and cognitive neuroscience. The purpose of this study was to compare changes in brain activation in the BG using results obtained from two different masking methods: a mask drawn in standardized space from a T1-weighted anatomical image and individual region of interest (ROI) masks drawn from each subject's echo-planar image (EPI) from different tasks with reference to the high resolution fast spin echo image of each subject. Two standardized masks were used: a mask developed in Talairach space (Basal Ganglia Human Area Template (BGHAT)) and a mask developed in Montreal Neurological Institute space (MNI mask). Ten subjects produced fingertip force pulses in five separate contraction tasks during fMRI scanning. ROIs were the left caudate, putamen, external and internal portions of the globus pallidus, and subthalamic nucleus. ANOVA revealed a similar average number of voxels in the EPI mask across tasks in each BG region. The percent signal change (PSC) was consistent within each region regardless of which mask was used. Linear regression analyses between PSC in BGHAT and EPI masks and MNI and EPI masks yielded r(2) values between 0.74-0.99 and 0.70-0.99 across regions, respectively. In conclusion, PSC in different BG ROIs can be compared across studies using these different masking methods. The masking method used does not affect the overall interpretation of results with respect to the effect of task. Use of a mask drawn in standardized space is a valid and time saving method of identifying PSC in the small nuclei of the BG. PMID:17988895

  9. 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.…

  10. 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. Clin. Anat. 29:481-492, 2016. © 2016 Wiley Periodicals, Inc. PMID:26779936

  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. PMID:26571268

  12. 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

  13. The Dopamine D1–D2 Receptor Heteromer in Striatal Medium Spiny Neurons: Evidence for a Third Distinct Neuronal Pathway in Basal Ganglia

    PubMed Central

    Perreault, Melissa L.; Hasbi, Ahmed; O’Dowd, Brian F.; George, Susan R.

    2011-01-01

    Dopaminergic signaling within the basal ganglia has classically been thought to occur within two distinct neuronal pathways; the direct striatonigral pathway which contains the dopamine D1 receptor and the neuropeptides dynorphin (DYN) and substance P, and the indirect striatopallidal pathway which expresses the dopamine D2 receptor and enkephalin (ENK). A number of studies have also shown, however, that D1 and D2 receptors can co-exist within the same medium spiny neuron and emerging evidence indicates that these D1/D2-coexpressing neurons, which also express DYN and ENK, may comprise a third neuronal pathway, with representation in both the striatonigral and striatopallidal projections of the basal ganglia. Furthermore, within these coexpressing neurons it has been shown that the dopamine D1 and D2 receptor can form a novel and pharmacologically distinct receptor complex, the dopamine D1–D2 receptor heteromer, with unique signaling properties. This is indicative of a functionally unique role for these neurons in brain. The aim of this review is to discuss the evidence in support of a novel third pathway coexpressing the D1 and D2 receptor, to discuss the potential relevance of this pathway to basal ganglia signaling, and to address its potential value, and that of the dopamine D1–D2 receptor heteromer, in the search for new therapeutic strategies for disorders involving dopamine neurotransmission. PMID:21747759

  14. Biomimetic race model of the loop between the superior colliculus and the basal ganglia: Subcortical selection of saccade targets.

    PubMed

    Thurat, Charles; N'Guyen, Steve; Girard, Benoît

    2015-07-01

    The superior colliculus, a laminar structure involved in the retinotopic mapping of the visual field, plays a cardinal role in several cortical and subcortical pathways of the saccadic system. Although the selection of saccade targets has long been thought to be mainly the product of cortical processes, a growing body of evidence hints at the implication of the superior colliculus in selection processes independent from cortical inputs, capable of producing saccades at latencies incompatible with the cortical pathways. This selection ability could be produced firstly by the lateral connections between the neurons of its maps, and secondly by its interactions with the midbrain basal ganglia, already renowned for their role in decision making. We propose a biomimetic population-coded race model of selection based on a dynamic tecto-basal loop that reproduces the observed ability of the superior colliculus to stochastically select between similar stimuli. Our model's selection accuracy depends on the discriminability of the target and the distractors. Our model also offers an explanation for the phenomenon of Remote Distractor Effect based on the lateral connectivity within the basal ganglia circuitry rather than on lateral inhibitions within the collicular maps. Finally, we propose a role for the intermediate layers of the superior colliculus, as stochastic integrators dynamically gated by the selective disinhibition of the basal ganglia channels that is consistent with the recorded activity profiles of these neurons. PMID:25884111

  15. Technical Integration of Hippocampus, Basal Ganglia and Physical Models for Spatial Navigation

    PubMed Central

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

    2008-01-01

    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. PMID:19333376

  16. Dopamine physiology in the basal ganglia of male zebra finches during social stimulation

    PubMed Central

    Ihle, Eva C; van der Hart, Marieke; Jongsma, Minke; Tecott, Larry H; Doupe, Allison J

    2015-01-01

    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. PMID:25872575

  17. 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

  18. Biotin-responsive basal ganglia disease should be renamed biotin-thiamine-responsive basal ganglia disease: a retrospective review of the clinical, radiological and molecular findings of 18 new cases

    PubMed Central

    2013-01-01

    Background Biotin-responsive basal ganglia disease (BBGD) is an autosomal recessive neurometabolic disorder. It is characterized by sub acute encephalopathy with confusion, seizure, dysarthria and dystonia following a history of febrile illness. If left untreated with biotin, the disease can progress to severe quadriparesis and even death. Method A retrospective chart review of 18 patients with BBGD from two tertiary institutions describing their clinical, magnetic resonance imaging and molecular findings was conducted. Result Eighteen children from 13 families seen over a period of nine years (2003–2012) were included. (Age range: 14month to 23 years, M: F: 1:1). The clinical features included sub acute encephalopathy, ataxia (n= 18), seizures (n= 13) dystonia (n=12) ,dysarthria (n= 9), quadriparesis and hyperreflexia (n=9). Magnetic resonance imaging demonstrated abnormal signal intensity with swelling in the basal ganglia during acute crises (n= 13/13) and atrophy of the basal ganglia and necrosis during follow up (n= 13/13). One-third of the present patients showed the recurrence of acute crises while on biotin therapy alone, but after the addition of thiamine, crises did not recur. All of the patients have a homozygous missense mutation in exon 5 of the SLC19A3 gene. The frequency of acute crises, delay in diagnosis and initiation of treatment significantly influenced the outcome. On follow up, four patients died, two had spastic quadriplegia, six had normal outcome and the rest had speech and motor dysfunctions. Conclusion Clinicians should suspect BBGD in any child presenting with sub acute encephalopathy, abnormal movement and MRI findings as described above. Both biotin and thiamine are essential for disease management. Since biotin alone could not prevent the recurrence of crises in some patients, a more appropriate term to describe the disease would be biotin-thiamine-responsive basal ganglia disease (BTBGD). PMID:23742248

  19. 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

  20. 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. PMID:19896804

  1. Late-Onset Mania in a Patient with Movement Disorder and Basal Ganglia Calcifications: A Challenge for Diagnosis and Treatment

    PubMed Central

    Roiter, Beatrice; Pigato, Giorgio; Perugi, Giulio

    2016-01-01

    Age of onset can have a significant impact on clinical course and pathophysiological mechanism of bipolar disorder. Late-onset bipolar episodes are more likely linked to medical illnesses and so are frequently classified as “secondary” forms of mood disorder. We discuss the case of a patient who at the age of 58 presented his first delusional-manic episode. He also had mild frontal and occipital cortical atrophy, white matter posterior ischemic lesions, and small basal ganglia calcifications. Seven years later, he presented a second manic episode with new emergent hyperkinetic choreiform symptoms. Taking into account movement disturbances, the presence of basal ganglia calcification, and worsening of cortical atrophy, we performed a differential diagnosis between Fahr disease, Fahr's syndrome, calcifications due to ageing, supersensitivity psychosis, and dementia. Valproate, quetiapine, and tetrabenazine were sequentially administered and yielded a good therapeutic response as regards manic and movement symptoms. Relationship between medications and course of specific symptoms was observed. PMID:27213069

  2. Basal Ganglia MR Relaxometry in Obsessive-Compulsive Disorder: T2 Depends Upon Age of Symptom Onset

    PubMed Central

    Hubbard, Emily; Hassenstab, Jason; Yip, Agustin; Vymazal, Josef; Herynek, Vit; Giedd, Jay; Murphy, Dennis L.; Greenberg, Benjamin D.

    2010-01-01

    Dysfunction in circuits linking frontal cortex and basal ganglia (BG) is strongly implicated in obsessive-compulsive disorder (OCD). On MRI studies, neuropsychiatric disorders with known BG pathology have abnormally short T2 relaxation values (a putative biomarker of elevated iron) in this region. We asked if BG T2 values are abnormal in OCD. We measured volume and T2 and T1 relaxation rates in BG of 32 adults with OCD and 33 matched controls. There were no group differences in volume or T1 values in caudate, putamen, or globus pallidus (GP). The OCD group had lower T2 values (suggesting higher iron content) in the right GP, with a trend in the same direction for the left GP. This effect was driven by patients whose OCD symptoms began from around adolescence to early adulthood. The results suggest a possible relationship between age of OCD onset and iron deposition in the basal ganglia. PMID:20503112

  3. Familial idiopathic basal ganglia calcification: Histopathologic features of an autopsied patient with an SLC20A2 mutation.

    PubMed

    Kimura, Tadashi; Miura, Takeshi; Aoki, Kenju; Saito, Shoji; Hondo, Hiroaki; Konno, Takuya; Uchiyama, Akio; Ikeuchi, Takeshi; Takahashi, Hitoshi; Kakita, Akiyoshi

    2016-08-01

    Idiopathic basal ganglia calcification (IBGC), or Fahr's disease, is a neurological disorder characterized by widespread calcification in the brain. Recently, several causative genes have been identified, but the histopathologic features of the brain lesions and expression of the gene products remain unclear. Here, we report the clinical and autopsy features of a 62-year-old Japanese man with familial IBGC, in whom an SLC20A2 mutation was identified. The patient developed mild cognitive impairment and parkinsonism. A brain CT scan demonstrated abnormal calcification in the bilateral basal ganglia, thalami and cerebellum. An MRI study at this point revealed glioblastoma, and the patient died 6 months later. At autopsy, symmetric calcification in the basal ganglia, thalami, cerebellar white matter and deeper layers of the cerebral cortex was evident. The calcification was observed in the tunica media of small arteries, arterioles and capillaries, but not in veins. Immunohistochemistry using an antibody against type III sodium-dependent phosphate transporter 2 (PiT-2), the SLC20A2 product, demonstrated that astrocytic processes were labeled in several regions in control brains, whereas in the patient, reactivity in astrocytes was apparently weak. Immunoblotting demonstrated a marked decrease of PiT-2 in the patient. There are few autopsy reports of IBGC patients with confirmation of the genetic background. The autopsy features seem informative for better understanding the histogenesis of IBGC lesions. PMID:26635128

  4. Neuronal activity (c-Fos) delineating interactions of the cerebral cortex and basal ganglia

    PubMed Central

    Qiu, Mei-Hong; Chen, Michael C.; Huang, Zhi-Li; Lu, Jun

    2014-01-01

    The cerebral cortex and basal ganglia (BG) form a neural circuit that is disrupted in disorders such as Parkinson’s disease. We found that neuronal activity (c-Fos) in the BG followed cortical activity, i.e., high in arousal state and low in sleep state. To determine if cortical activity is necessary for BG activity, we administered atropine to rats to induce a dissociative state resulting in slow-wave electroencephalography but hyperactive motor behaviors. Atropine blocked c-Fos expression in the cortex and BG, despite high c-Fos expression in the sub-cortical arousal neuronal groups and thalamus, indicating that cortical activity is required for BG activation. To identify which glutamate receptors in the BG that mediate cortical inputs, we injected ketamine [N-methyl-d-aspartate (NMDA) receptor antagonist] and 6-cyano-nitroquinoxaline-2, 3-dione (CNQX, a non-NMDA receptor antagonist). Systemic ketamine and CNQX administration revealed that NMDA receptors mediated subthalamic nucleus (STN) input to internal globus pallidus (GPi) and substantia nigra pars reticulata (SNr), while non-NMDA receptor mediated cortical input to the STN. Both types of glutamate receptors were involved in mediating cortical input to the striatum. Dorsal striatal (caudoputamen, CPu) dopamine depletion by 6-hydroxydopamine resulted in reduced activity of the CPu, globus pallidus externa (GPe), and STN but increased activity of the GPi, SNr, and putative layer V neurons in the motor cortex. Our results reveal that the cortical activity is necessary for BG activity and clarifies the pathways and properties of the BG-cortical network and their putative role in the pathophysiology of BG disorders. PMID:24723855

  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. Clinical significance of blood supply to the internal capsule and basal ganglia.

    PubMed

    Djulejić, Vuk; Marinković, Slobodan; Georgievski, Biljana; Stijak, Lazar; Aksić, Milan; Puškaš, Laslo; Milić, Ivan

    2016-03-01

    Although the general vascular supply of the basal ganglia and internal capsule is well known, precise data are lacking regarding the variations of the vascular territories in the two regions. Twelve hemispheres were studied following an injection of coloured ink into the main cerebral arteries, namely the anterior cerebral (ACA), middle cerebral (MCA), anterior choroidal (AChA) and posterior cerebral artery (PCA). Serial sections of the injected hemispheres were taken in the axial or coronal plane. In 75% of the hemispheres, ACA perforators were seen to supply the inferomedial part of the head of the caudate nucleus and the anterior limb of the internal capsule, as well as the anterior and inferior portions of the putamen and globus pallidus. The MCA vessels perfused the superolateral part of the head and body of the caudate nucleus, the superior part of the entire internal capsule, most of the putamen and part of the globus pallidus. The AChA perforators perfused the medial segment of the globus pallidus, the inferior part of the posterior limb, the retrolenticular and sublenticular portions of the internal capsule, and occasionally its genu. The same segment of the globus pallidus and the inferior part of the genu of the internal capsule were most likely supplied by the perforators of the internal carotid artery. A predominance of ACA territory was noticed in one specimen (8.33%) and a predominance of MCA territory in two specimens (16.67%). The obtained anatomical data may help radiologic determination of perforators involved in ischemic events, as well as a better understanding of the neurological deficits in the same events. PMID:26596401

  7. Ultra-high field magnetic resonance imaging of the basal ganglia and related structures

    PubMed Central

    Plantinga, Birgit R.; Temel, Yasin; Roebroeck, Alard; Uludağ, Kâmil; Ivanov, Dimo; Kuijf, Mark L.; ter Haar Romenij, Bart M.

    2014-01-01

    Deep brain stimulation is a treatment for Parkinson's disease and other related disorders, involving the surgical placement of electrodes in the deeply situated basal ganglia or thalamic structures. Good clinical outcome requires accurate targeting. However, due to limited visibility of the target structures on routine clinical MR images, direct targeting of structures can be challenging. Non-clinical MR scanners with ultra-high magnetic field (7T or higher) have the potential to improve the quality of these images. This technology report provides an overview of the current possibilities of visualizing deep brain stimulation targets and their related structures with the aid of ultra-high field MRI. Reviewed studies showed improved resolution, contrast- and signal-to-noise ratios at ultra-high field. Sequences sensitive to magnetic susceptibility such as T2* and susceptibility weighted imaging and their maps in general showed the best visualization of target structures, including a separation between the subthalamic nucleus and the substantia nigra, the lamina pallidi medialis and lamina pallidi incompleta within the globus pallidus and substructures of the thalamus, including the ventral intermediate nucleus (Vim). This shows that the visibility, identification, and even subdivision of the small deep brain stimulation targets benefit from increased field strength. Although ultra-high field MR imaging is associated with increased risk of geometrical distortions, it has been shown that these distortions can be avoided or corrected to the extent where the effects are limited. The availability of ultra-high field MR scanners for humans seems to provide opportunities for a more accurate targeting for deep brain stimulation in patients with Parkinson's disease and related disorders. PMID:25414656

  8. Neurobrucellosis with transient ischemic attack, vasculopathic changes, intracerebral granulomas and basal ganglia infarction: a case report

    PubMed Central

    2010-01-01

    Introduction Central nervous system involvement is a rare but serious manifestation of brucellosis. We present an unusual case of neurobrucellosis with transient ischemic attack, intracerebral vasculopathy granulomas, seizures, and paralysis of sixth and seventh cranial nerves. Case presentation A 17-year-old Caucasian man presented with nausea and vomiting, headache, double vision and he gave a history of weakness in the left arm, speech disturbance and imbalance. Physical examination revealed fever, doubtful neck stiffness and left abducens nerve paralysis. An analysis of his cerebrospinal fluid showed a pleocytosis (lymphocytes, 90%), high protein and low glucose levels. He developed generalized tonic-clonic seizures, facial paralysis and left hemiparesis. Cranial magnetic resonance imaging demonstrated intracerebral vasculitis, basal ganglia infarction and granulomas, mimicking the central nervous system involvement of tuberculosis. On the 31st day of his admission, neurobrucellosis was diagnosed with immunoglobulin M and immunoglobulin G positivity by standard tube agglutination test and enzyme-linked immunosorbent assay in both serum and cerebrospinal fluid samples (the tests had been negative until that day). He was treated successfully with trimethoprim and sulfamethoxazole, doxycyline and rifampicin for six months. Conclusions Our patient illustrates the importance of suspecting brucellosis as a cause of meningoencephalitis, even if cultures and serological tests are negative at the beginning of the disease. As a result, in patients who have a history of residence or travel to endemic areas, neurobrucellosis should be considered in the differential diagnosis of any neurologic symptoms. If initial tests fail, repetition of these tests at appropriate intervals along with complementary investigations are indicated. PMID:20973948

  9. Basal ganglia contribution to rule expectancy and temporal predictability in speech.

    PubMed

    Kotz, Sonja A; Schmidt-Kassow, Maren

    2015-07-01

    The current work set out to answer three questions: (1) Are reported syntactic deficits in patients with structural damage to the basal ganglia (BG) in the cortico-striato-thalamo-cortical systems (CSTCS) the result of a syntax specific computational deficit or are they potentially a consequence of a generalized timing deficit? (2) Do BG patients suffer from a simple beat perception deficit in speech comparable to the one reported in music? (3) Can regular speech meter (i.e., a pattern of beats induced by the regular alteration of stressed and unstressed syllable accents) ameliorate the computation of syntactically marked information by making speech events temporally predictable and salient? The latter 'remediation' hypothesis would predict that when speech events (i.e., those that are syntactically marked) are metrically aligned to the syllabic accent structure, the computation of syntactic information is facilitated or in the case of patients ameliorated. During continuous EEG measurement nineteen patients with focal BG lesions and matched healthy controls listened to metrically regular and syntactically well-formed sentences and metrically well-formed sentences that either violated syntactic expectancy, metrical expectancy, or both. While healthy controls showed an expected P600 response in the event-related brain potential (ERP) to all expectancy violations, BG patients showed overall comparable P600 responses to all, but the metrical expectancy violation. These results confirm that (1) BG patients suffer from a simple beat perception deficit in speech and (2) regular speech meter ameliorates the computation of syntactically marked information in the speech signal. We propose that a domain general sensorimotor cerebello-thalamo-cortical system (CTCS), involved in event-based temporal processing, engages in the remediation of dysfunctional cortico-striato-thalamo-cortical timing that affects the timely computation of linguistic (i.e., syntax) information in the

  10. 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. PMID:25205331

  11. Event-related potential activity in the basal ganglia differentiates rewards from nonrewards: temporospatial principal components analysis and source localization of the feedback negativity: commentary.

    PubMed

    Cohen, Michael X; Cavanagh, James F; Slagter, Heleen A

    2011-12-01

    Foti et al. propose that a reward-related brain potential component recorded from scalp EEG is generated by deep brain basal ganglia structures. Previous work, cited in their original article, provides only speculative and theoretical support for this interpretation. Based on empirical and anatomical evidence, we argue that this scalp-recorded ERP component is highly unlikely to be generated by the basal ganglia. PMID:21826758

  12. Correlation of iron deposition and change of gliocyte metabolism in the basal ganglia region evaluated using magnetic resonance imaging techniques: an in vivo study

    PubMed Central

    Liu, Haodi

    2016-01-01

    Introduction We assessed the correlation between iron deposition and the change of gliocyte metabolism in healthy subjects’ basal ganglia region, by using 3D-enhanced susceptibility weighted angiography (ESWAN) and proton magnetic resonance spectroscopy (1H-MRS). Material and methods Seventy-seven healthy volunteers (39 female and 38 male subjects; age range: 24–82 years old) were enrolled in the experiment including ESWAN and proton MRS sequences, consent for which was provided by themselves or their guardians. For each subject, the mean phase value gained by ESWAN was used to evaluate the iron deposition; choline/creatine (Cho/Cr) and mI/Cr ratios gained by 1H-MRS were used to evaluate gliocyte metabolism in the basal ganglia region of both sides. The paired t test was used to test the difference between the two sides of the basal ganglia region. Linear regression was performed to evaluate the relation between mean phase value and age. Pearson's correlation coefficient was calculated to analyze the relationship between the result of ESWAN and 1H-MRS. Results There was no difference between the two sides of the basal ganglia region in the mean phase value and Cho/Cr. But in mI/Cr the mean phase value of each nucleus in bilateral basal ganglia decreased with increasing age. There are 16 r-values between the mean phase value and Cho/Cr and mI/Cr in bilateral basal ganglia region. And each of all p-values is less than 0.001 (p < 0.001). Conclusions Iron deposition in the bilateral basal ganglia is associated with the change of gliocyte metabolism with increasing age. Iron deposition in each nucleus of the basal ganglia region changes with age. PMID:26925133

  13. The Allocation of Attention to Learning of Goal-Directed Actions: A Cognitive Neuroscience Framework Focusing on the Basal Ganglia

    PubMed Central

    Franz, E. A.

    2012-01-01

    The present paper builds on the idea that attention is largely in service of our actions. A framework and model which captures the allocation of attention for learning of goal-directed actions is proposed and developed. This framework highlights an evolutionary model based on the notion that rudimentary functions of the basal ganglia have become embedded into increasingly higher levels of networks which all contribute to adaptive learning. Supporting the proposed model, background literature is presented alongside key evidence based on experimental studies in the so-called “split-brain” (surgically divided cerebral hemispheres), and selected evidence from related areas of research. Although overlap with other existing findings and models is acknowledged, the proposed framework is an original synthesis of cognitive experimental findings with supporting evidence of a neural system and a carefully formulated model of attention. It is the hope that this new synthesis will be informative in fields of cognition and other fields of brain sciences and will lead to new avenues for experimentation across domains. PMID:23267335

  14. MR imaging and spectroscopy of the basal ganglia in chronic liver disease: correlation of T1-weighted contrast measurements with abnormalities in proton and phosphorus-31 MR spectra.

    PubMed

    Taylor-Robinson, S D; Sargentoni, J; Oatridge, A; Bryant, D J; Hajnal, J V; Marcus, C D; Seery, J P; Hodgson, H J; deSouza, N M

    1996-09-01

    The purpose of this study was to correlate the hyperintensity in the globus pallidus seen on T1-weighted magnetic resonance imaging (MRI) of the brain in chronic liver disease with changes in metabolite ratios measured from both proton and phosphorus-31 magnetic resonance spectroscopy (MRS) localised to the basal ganglia. T1-weighted spin echo (T1WSE) images were obtained in 21 patients with biopsy-proven cirrhosis (nine Child's grade A, eight Child's grade B and four Child's grade C). Four subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, four showed evidence of subclinical hepatic encephalopathy and 13 had overt hepatic encephalopathy. Signal intensities of the globus pallidus and adjacent brain parenchyma were measured and contrast calculated, which correlated with the severity of the underlying liver disease, when graded according to the Pugh's score (p < 0.05). Proton MRS of the basal ganglia was performed in 12 patients and 14 healthy volunteers. Peak area ratios of choline (Cho), glutamine and glutamate (Glx) and N-acetylaspartate relative to creatine (Cr) were measured. Significant reductions in mean Cho/Cr and elevations in mean Glx/Cr ratios were observed in the patient population. Phosphorus-31 MRS of the basal ganglia was performed in the remaining nine patients and in 15 healthy volunteers. Peak area ratios of phosphomonoesters (PME), inorganic phosphate, phosphodiesters (PDE) and phosphocreatine relative to beta ATP (ATP) were then measured. Mean values of PME/ATP and PDE/ATP were significantly lower in the patient population. No correlation was found between the T1WSE MRI contrast measurements of the globus pallidus and the abnormalities in the metabolite ratios measured from either proton or phosphorus-31 MR spectra. Our results suggest that pallidal hyperintensity seen on T1WSE MR imaging of patients with chronic liver disease is not related to the functional abnormalities of the

  15. 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

  16. 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. PMID:20883725

  17. Interactions between Cortical Rhythms and Spiking Activity of Single Basal Ganglia Neurons in the Normal and Parkinsonian State

    PubMed Central

    Gatev, Plamen

    2009-01-01

    In order to evaluate the specific interactions between cortical oscillations and basal ganglia–spiking activity under normal and parkinsonian conditions, we examined the relationship between frontal cortex electroencephalographic (EEG) signals and simultaneously recorded neuronal activity in the internal and external segments of the pallidum or the subthalamic nucleus (STN) in 3 rhesus monkeys. After we made recordings in the normal state, hemiparkinsonism was induced with intracarotid injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in one animal, followed by additional recordings. Spiking activity in the pallidum and STN was associated with significant shifts in the level of EEG synchronization. We also found that the spectral power of beta- and gamma-band EEG rhythms covaried positively before the basal ganglia spikes but did not covary or covaried negatively thereafter. In parkinsonism, changes in cortical synchronization and phase coherence were reduced in EEG segments aligned to STN spikes, whereas both were increased in data segments aligned to pallidal spikes. Spiking-related changes in beta/gamma-band covariance were reduced. The findings indicate that basal ganglia and cortex interact in the processing of cortical rhythms that contain oscillations across a broad range of frequencies and that this interaction is severely disrupted in parkinsonism. PMID:18842667

  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. Emergent structured transition from variation to repetition in a biologically-plausible model of learning in basal ganglia

    PubMed Central

    Shah, Ashvin; Gurney, Kevin N.

    2014-01-01

    Often, when animals encounter an unexpected sensory event, they transition from executing a variety of movements to repeating the movement(s) that may have caused the event. According to a recent theory of action discovery (Redgrave and Gurney, 2006), repetition allows the animal to represent those movements, and the outcome, as an action for later recruitment. The transition from variation to repetition often follows a non-random, structured, pattern. While the structure of the pattern can be explained by sophisticated cognitive mechanisms, simpler mechanisms based on dopaminergic modulation of basal ganglia (BG) activity are thought to underlie action discovery (Redgrave and Gurney, 2006). In this paper we ask the question: can simple BG-mediated mechanisms account for a structured transition from variation to repetition, or are more sophisticated cognitive mechanisms always necessary? To address this question, we present a computational model of BG-mediated biasing of behavior. In our model, unlike most other models of BG function, the BG biases behavior through modulation of cortical response to excitation; many possible movements are represented by the cortical area; and excitation to the cortical area is topographically-organized. We subject the model to simple reaching tasks, inspired by behavioral studies, in which a location to which to reach must be selected. Locations within a target area elicit a reinforcement signal. A structured transition from variation to repetition emerges from simple BG-mediated biasing of cortical response to excitation. We show how the structured pattern influences behavior in simple and complicated tasks. We also present analyses that describe the structured transition from variation to repetition due to BG-mediated biasing and from biasing that would be expected from a type of cognitive biasing, allowing us to compare behavior resulting from these types of biasing and make connections with future behavioral experiments. PMID

  20. Action selection performance of a reconfigurable basal ganglia inspired model with Hebbian-Bayesian Go-NoGo connectivity.

    PubMed

    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

  1. Chromosome 10p deletion in a patient with hypoparathyroidism, severe mental retardation, autism and basal ganglia calcifications.

    PubMed

    Verri, Annapia; Maraschio, Paola; Devriendt, Koen; Uggetti, Carla; Spadoni, Emanuela; Haeusler, Edward; Federico, Antonio

    2004-01-01

    Chromosome 10p terminal deletions have been associated with a DiGeorge like phenotype. Haploinsufficiency of the region 10p14-pter, results in hypoparathyroidism, sensorineural deafness, renal anomaly, that is the triad that features the HDR syndrome. Van Esch (2000) identified in a HDR patient, within a 200 kb critical region, the GATA3 gene, a transcription factor involved in the embryonic development of the parathyroids, auditory system and kidneys. We describe a new male patient, 33-year-old, with 10p partial deletion affected by hypocalcemia, basal ganglia calcifications and a severe autistic syndrome associated with mental retardation. Neurologically he presented severe impairment of language, hypotonia, clumsiness and a postural dystonic attitude. A peripheral involvement of auditory pathways was documented by auditory evoked potentials alterations. CT scan documented basal ganglia calcifications. Hyperintensity of the lentiform nuclei was evident at the MRI examination. Renal ultrasound scan was normal. Haploinsufficiency for GATA3 gene was documented with FISH analysis using cosmid clone 1.2. Phenotypic spectrum observed in del (10p) is more severe than the classical DGS spectrum. GATA3 has been found to regulate the development of serotoninergic neurons. A serotoninergic dysfunction may be linked with autism in this patient. PMID:15337474

  2. Impaired L1 and executive control after left basal ganglia damage in a bilingual Basque-Spanish person with aphasia.

    PubMed

    Adrover-Roig, Daniel; Galparsoro-Izagirre, Nekane; Marcotte, Karine; Ferré, Perrine; Wilson, Maximiliano A; Inés Ansaldo, Ana

    2011-06-01

    Bilinguals must focus their attention to control competing languages. In bilingual aphasia, damage to the fronto-subcortical loop may lead to pathological language switching and mixing and the attrition of the more automatic language (usually L1). We present the case of JZ, a bilingual Basque-Spanish 53-year-old man who, after haematoma in the left basal ganglia, presented with executive deficits and aphasia, characterised by more impaired language processing in Basque, his L1. Assessment with the Bilingual Aphasia Test revealed impaired spontaneous and automatic speech production and speech rate in L1, as well as impaired L2-to-L1 sentence translation. Later observation led to the assessment of verbal and non-verbal executive control, which allowed JZ's impaired performance on language tasks to be related to executive dysfunction. In line with previous research, we report the significant attrition of L1 following damage to the left basal ganglia, reported for the first time in a Basque-Spanish bilingual. Implications for models of declarative and procedural memory are discussed. PMID:21453016

  3. Treatment Efficacy of the Transsylvian Approach Versus the Transtemporal Cortex Approach to Evacuate Basal Ganglia Hematoma Under a Microscope.

    PubMed

    Xu, Tao; Liu, Hao; Peng, Lin; Li, Hao; Wang, Jiying; Jiang, Yong; Gu, Yingjiang

    2016-03-01

    This study aimed to evaluate the clinical efficacy of the transsylvian approach versus the transtemporal cortex approach to evacuate basal ganglia hemorrhage under a microscope. The relevant literature was collected from PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature database, and China National Knowledge Infrastructure databases. The meta-analysis was conducted by Stata 12.0 software. Seven studies were included in the meta-analysis. There were 659 patients, including 329 patients who were treated by the transsylvian approach and 330 patients who were treated by the transtemporal cortex approach. There were significant advantages in the transsylvian approach group, including a high clearance rate of hematoma (OR = 2.361; 95% CI: 1.443-3.861) and a better postoperative recovery (OR = 2.248; 95% CI: 1.598-3.160). A better postoperative recovery could also be found in patients with a history of hypertension (OR = 2.063; 95% CI: 1.429-2.980) and patients whose volume of hematoma ranged from 25 to 60 mL (OR = 2.275; 95% CI: 1.466-3.529). The authors conclude that there are significant advantages to the transsylvian approach, such as a high clearance rate of hematoma and a good postoperative recovery. These advantages should be taken into account when devising appropriate therapeutic strategies for patients with basal ganglia hematoma. PMID:26967068

  4. Changes in total cell numbers of the basal ganglia in patients with multiple system atrophy - A stereological study.

    PubMed

    Salvesen, Lisette; Ullerup, Birgitte H; Sunay, Fatma B; Brudek, Tomasz; Løkkegaard, Annemette; Agander, Tina K; Winge, Kristian; Pakkenberg, Bente

    2015-02-01

    Total numbers of neurons, oligodendrocytes, astrocytes, and microglia in the basal ganglia and red nucleus were estimated in brains from 11 patients with multiple system atrophy (MSA) and 11 age- and gender-matched control subjects with unbiased stereological methods. Compared to the control subjects, the MSA patients had a substantially lower number of neurons in the substantia nigra (p=0.001), putamen (p=0.001), and globus pallidus (p<0.001), and, to a lesser extent in the caudate nucleus (p=0.03). A significantly lower number of oligodendrocytes were only observed in the putamen (p=0.04) and globus pallidus (p=0.01). In the MSA brains the total number of astrocytes was significantly higher in the putamen (p=0.04) and caudate nucleus (p=0.01). In all examined regions a higher number of microglia were found in the MSA brains with the greatest difference observed in the otherwise unaffected red nucleus (p=0.001). The results from the stereological study were supported by cell marker expression analyses showing increased markers for activated microglia. Our results suggest that microgliosis is a consistent and severe neuropathological feature of MSA, whereas no widespread and substantial loss of oligodendrocytes was observed. We have demonstrated significant neuronal loss in the substantia nigra, striatum, and globus pallidus of patients with MSA, while neurons in other basal ganglia nuclei were spared, supporting the region-specific patterns of neuropathological changes in MSA. PMID:25449905

  5. A case of traumatic hematoma in the basal ganglia that showed deterioration after arrival at the hospital.

    PubMed

    Moriya, Takashi; Tagami, Rumi; Furukawa, Makoto; Sakurai, Atsushi; Kinoshita, Kosaku; Tanjoh, Katsuhisa

    2013-01-01

    A case of traumatic hematoma in the basal ganglia that showed deterioration after arrival at the hospital was reported. A 65-year-old man crashed into the wall while riding a motorcycle. His Glasgow coma scale was E3V4M6 and showed retrograde amnesia and slight right motor weakness. Because head CT in the secondary trauma survey showed subarachnoid hemorrhage in the right Sylvian fissure and multiple gliding contusions in the left frontal and parietal lobe, he was entered into the intensive care unit for diagnosis of diffuse brain injury. He showed complete muscle weakness of left upper and lower limbs 5 h after the accident. Head CT newly showed hematoma, 2 cm in diameter, in the right basal ganglia. The patient vomited following the CT scan, and so his consciousness suddenly deteriorated into a stupor. We performed head CT again. The hematoma had enlarged to 5 cm at the same lesion and partially expanded into midbrain. The patient died on the 13th day of trauma. Based on retrospective interpretation, we conclude that clinical examinations, follow-up CT scans and blood examinations should be performed frequently as part of ICU management for all TBI patients in the early phase after trauma. PMID:23564122

  6. 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. PMID:1960538

  7. Idiopathic basal ganglia calcification presenting as schizophrenia-like psychosis and obsessive-compulsive symptoms: A case report

    PubMed Central

    PAN, BING; LIU, WEIBO; CHEN, QIAOZHEN; ZHENG, LEILEI; BAO, YINGYING; LI, HUICHUN; YU, RISHENG

    2015-01-01

    Idiopathic basal ganglia calcification (IBGC) is a rare neurodegenerative disorder characterized by the deposition of calcium in the brain and variable combinations of movement disorders, gait impairment and neuropsychiatric symptoms. Few reports have described psychiatric manifestations as early symptoms of IBGC. The present study reports the case of a middle-aged man with schizophrenia-like psychosis and obsessive-compulsive symptoms as the first manifestations of IBGC. The response of the patient to olanzapine and fluoxetine suggests that low-dose olanzapine is effective and should be increased cautiously to avoid worsening parkinsonism and that fluoxetine is an effective drug for the treatment of obsessive-compulsive symptoms in IBGC. PMID:26622362

  8. A computational model of Parkinsonian handwriting that highlights the role of the indirect pathway in the basal ganglia.

    PubMed

    Gangadhar, G; Joseph, D; Srinivasan, A V; Subramanian, D; Shivakeshavan, R G; Shobana, N; Chakravarthy, V S

    2009-10-01

    Parkinsonian handwriting is typically characterized by micrographia, jagged line contour, and unusual fluctuations in pen velocity. In this paper we present a computational model of handwriting generation that highlights the role of the basal ganglia, particularly the indirect pathway. Whereas reduced dopamine levels resulted in reduced letter size, transition of STN-GPe dynamics from desynchronized (normal) to synchronized (PD) condition resulted in increased fluctuations in velocity in the model. We also present handwriting data from PD patients (n=34) who are at various stages of disease and had taken medication various lengths of time before the handwriting sessions. The patient data are compared with those of age-matched controls. PD handwriting statistically exhibited smaller size and larger velocity fluctuation compared to normal handwriting. PMID:19720411

  9. Calcification of basal ganglia and cerebellar roof nuclei in mentally defective patient with hidrotic ectodermal dysplasia. Analysis of intracranial concretions by electon microprobe.

    PubMed

    Copeland, D D; Lamb, W A; Klintworth, G K

    1977-11-01

    This report describes, for the first time, an analysis by electron microprobe of concretions in the brain of an individual with striopallidodentate calcification. We also report the unique association of this intracranial syndrome with hidrotic ectodermal dysplasia. An institutionalized male with impaired intellectual function and hidrotic ectodermal dysplasia was known since the age of 3 years to have bilateral radiopaque densities in the region of the basal ganglia on skull roentgenogram. He died at age 29 in congestive heart failure from rheumatic pancarditis. At autopsy, concretions were identified in globus pallidus, caudate nuclei, thalamus, and dentate nuclei. Mineral deposits within the brain, analyzed by energy dispersive x-ray microanalysis, consisted predominately of calcium and phosphorus. Trace amounts of magnesium, iron, and silicon also were detected. PMID:562997

  10. Behavioural effects of basal ganglia rho-kinase inhibition in the unilateral 6-hydroxydopamine rat model of Parkinson's disease.

    PubMed

    Inan, Salim Yalcin; Soner, Burak Cem; Sahin, Ayse Saide

    2016-08-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders, which affects more than six million people in the world. While current available pharmacological therapies for PD in the early stages of the disease usually improve motor symptoms, they cause side effects, such as fluctuations and dyskinesias in the later stages. In this later stage, high frequency deep brain stimulation of the subthalamic nucleus (STN-DBS) is a treatment option which is most successful to treat drug resistant advanced PD. It has previously been demonstrated that activation of Rho/Rho-kinase pathway is involved in the dopaminergic cell degeneration which is one of the main characteristics of PD pathology. In addition, the involvement of this pathway has been suggested in diverse cellular events in the central nervous system; such as epilepsy, anxiety-related behaviors, regulation of dendritic and axonal morphology, antinociception, subarachnoid haemorrhage, spinal cord injury and amyotrophic lateral sclerosis. However, up to date, to our knowledge there are no previous reports showing the beneficial effects of the potent Rho-kinase inhibitor Y-27632 in the 6-hydroxydopamine (6-OHDA) rat model of PD. Therefore, in the present study, we investigated the behavioural effects of basal ganglia Y-27632 microinjections in this PD model. Our results indicated that basal ganglia Y-27632 microinjections significantly decreased the number of contralateral rotations-induced by apomorphine, significantly increased line crossings in the open-field test, contralateral forelimb use in the limb-use asymmetry test and contralateral tape playing time in the somatosensory asymmetry test, which may suggest that Y-27632 could be a potentially active antiparkinsonian agent. PMID:26996632

  11. Basal ganglia calcification induced by excitotoxicity: an experimental model characterised by electron microscopy and X-ray microanalysis.

    PubMed

    Mahy, N; Prats, A; Riveros, A; Andrés, N; Bernal, F

    1999-09-01

    Activation of glutamate receptors induces an excitotoxic neurodegenerative process characterised in some brain areas by the formation of calcium precipitates. To examine the pathogenesis of basal ganglia calcification (BGC), an improved procedure of X-ray microanalysis was used to study experimental excitotoxic calcification in the rat. Three weeks after injection of ibotenic acid (IBO) in the rat basal forebrain, calcified inclusions within hypertrophied astrocytes were characterised. They appeared to form part of a filamentous structure localised in the cytoplasm in association with normal mitochondria and other organelles. Larger inclusions were surrounded by reactive microglia. The main inorganic components in these deposits were Ca and P, frequently accompanied by S. Al, Si and K. The shape and Ca/P molar ratio of the large deposits (>10 microm) indicate that they may be biological apatites. Aluminosilicates were detected as small deposits (<4 microm) free of other mineral constituents. To our knowledge this is the first report showing that IBO lesion induces brain accumulation of aluminosilicates similar to that described in Alzheimer's or Fahr's patients. Our data indicate that precipitation of Ca and Al may reduce their IBO-induced increased concentration. In conclusion, the experimental model and the improved efficiency of X-ray analysis described may help us to understand the pathogenesis of BGC. PMID:10483777

  12. 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. PMID:22845853

  13. Model-based analysis and control of a network of basal ganglia spiking neurons in the normal and Parkinsonian states

    NASA Astrophysics Data System (ADS)

    Liu, Jianbo; Khalil, Hassan K.; Oweiss, Karim G.

    2011-08-01

    Controlling the spatiotemporal firing pattern of an intricately connected network of neurons through microstimulation is highly desirable in many applications. We investigated in this paper the feasibility of using a model-based approach to the analysis and control of a basal ganglia (BG) network model of Hodgkin-Huxley (HH) spiking neurons through microstimulation. Detailed analysis of this network model suggests that it can reproduce the experimentally observed characteristics of BG neurons under a normal and a pathological Parkinsonian state. A simplified neuronal firing rate model, identified from the detailed HH network model, is shown to capture the essential network dynamics. Mathematical analysis of the simplified model reveals the presence of a systematic relationship between the network's structure and its dynamic response to spatiotemporally patterned microstimulation. We show that both the network synaptic organization and the local mechanism of microstimulation can impose tight constraints on the possible spatiotemporal firing patterns that can be generated by the microstimulated network, which may hinder the effectiveness of microstimulation to achieve a desired objective under certain conditions. Finally, we demonstrate that the feedback control design aided by the mathematical analysis of the simplified model is indeed effective in driving the BG network in the normal and Parskinsonian states to follow a prescribed spatiotemporal firing pattern. We further show that the rhythmic/oscillatory patterns that characterize a dopamine-depleted BG network can be suppressed as a direct consequence of controlling the spatiotemporal pattern of a subpopulation of the output Globus Pallidus internalis (GPi) neurons in the network. This work may provide plausible explanations for the mechanisms underlying the therapeutic effects of deep brain stimulation (DBS) in Parkinson's disease and pave the way towards a model-based, network level analysis and closed

  14. Novel SLC19A3 Promoter Deletion and Allelic Silencing in Biotin-Thiamine-Responsive Basal Ganglia Encephalopathy

    PubMed Central

    Flønes, Irene; Sztromwasser, Paweł; Haugarvoll, Kristoffer; Dölle, Christian; Lykouri, Maria; Schwarzlmüller, Thomas; Jonassen, Inge; Miletic, Hrvoje; Johansson, Stefan; Knappskog, Per M.; Bindoff, Laurence A.; Tzoulis, Charalampos

    2016-01-01

    Background Biotin-thiamine responsive basal ganglia disease is a severe, but potentially treatable disorder caused by mutations in the SLC19A3 gene. Although the disease is inherited in an autosomal recessive manner, patients with typical phenotypes carrying single heterozygous mutations have been reported. This makes the diagnosis uncertain and may delay treatment. Methods and Results In two siblings with early-onset encephalopathy dystonia and epilepsy, whole-exome sequencing revealed a novel single heterozygous SLC19A3 mutation (c.337T>C). Although Sanger-sequencing and copy-number analysis revealed no other aberrations, RNA-sequencing in brain tissue suggested the second allele was silenced. Whole-genome sequencing resolved the genetic defect by revealing a novel 45,049 bp deletion in the 5’-UTR region of the gene abolishing the promoter. High dose thiamine and biotin therapy was started in the surviving sibling who remains stable. In another patient two novel compound heterozygous SLC19A3 mutations were found. He improved substantially on thiamine and biotin therapy. Conclusions We show that large genomic deletions occur in the regulatory region of SLC19A3 and should be considered in genetic testing. Moreover, our study highlights the power of whole-genome sequencing as a diagnostic tool for rare genetic disorders across a wide spectrum of mutations including non-coding large genomic rearrangements. PMID:26863430

  15. 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

  16. Hyporesponsive Reward Anticipation in the Basal Ganglia following Severe Institutional Deprivation Early in Life

    ERIC Educational Resources Information Center

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

    2010-01-01

    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…

  17. 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. PMID:25389391

  18. 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

  19. Endoscopic surgery versus conservative treatment for the moderate-volume hematoma in spontaneous basal ganglia hemorrhage (ECMOH): study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Spontaneous intracerebral hemorrhage is a disease with high morbidity, high disability rate, high mortality, and high economic burden. Whether patients can benefit from surgical evacuation of hematomas is still controversial, especially for those with moderate-volume hematomas in the basal ganglia. This study is designed to compare the efficacy of endoscopic surgery and conservative treatment for the moderate-volume hematoma in spontaneous basal ganglia hemorrhage. Methods Patients meet the criteria will be randomized into the endoscopic surgery group (endoscopic surgery for hematoma evacuation and the best medical treatment) or the conservative treatment group (the best medical treatment). Patients will be followed up at 1, 3, and 6 months after initial treatment. The primary outcomes include the Extended Glasgow Outcome Scale and the Modified Rankin Scale. The secondary outcomes consist of the National Institutes of Health Stroke Scale and the mortality. The Barthel Index(BI) will also be evaluated. The sample size is 100 patients. Discussion The ECMOH trial is a randomized controlled trial designed to evaluate if endoscopic surgery is better than conservative treatment for patients with moderate-volume hematomas in the basal ganglia. Trial registration Chinese Clinical Trial Registry: ChiCTR-TRC-11001614 (http://www.chictr.org/en/proj/show.aspx?proj=1618) PMID:22676908

  20. Ether-à-go-go 1 (Eag1) potassium channel expression in dopaminergic neurons of basal ganglia is modulated by 6-hydroxydopamine lesion.

    PubMed

    Ferreira, N R; Mitkovski, M; Stühmer, W; Pardo, L A; Del Bel, E A

    2012-04-01

    The ether à go-go (Eag) gene encodes the voltage-gated potassium (K(+)) ion channel Kv10.1, whose function still remains unknown. As dopamine may directly affect K(+) channels, we evaluated whether a nigrostriatal dopaminergic lesion induced by the neurotoxin 6-hydroxydopamine (6-OHDA) would alter Eag1-K(+) channel expression in the rat basal ganglia and related brain regions. Male Wistar rats received a microinjection of either saline or 6-OHDA (unilaterally) into the medial forebrain bundle. The extent of the dopaminergic lesion induced by 6-OHDA was evaluated by apomorphine-induced rotational behavior and by tyrosine hydroxylase (TH) immunoreactivity. The 6-OHDA microinjection caused a partial or complete lesion of dopaminergic cells, as well as a reduction of Eag1+ cells in a manner proportional to the extent of the lesion. In addition, we observed a decrease in TH immunoreactivity in the ipsilateral striatum. In conclusion, the expression of the Eag1-K(+)-channel throughout the nigrostriatal pathway in the rat brain, its co-localization with dopaminergic cells and its reduction mirroring the extent of the lesion highlight a physiological circuitry where the functional role of this channel can be investigated. The Eag1-K(+) channel expression in dopaminergic cells suggests that these channels are part of the diversified group of ion channels that generate and maintain the electrophysiological activity pattern of dopaminergic midbrain neurons. PMID:22048886

  1. A probabilistic atlas of the basal ganglia using 7 T MRI

    PubMed Central

    Keuken, Max C.; Forstmann, Birte U.

    2015-01-01

    A common localization procedure in functional imaging studies includes the overlay of statistical parametric functional magnetic resonance imaging (fMRI) maps or coordinates with neuroanatomical atlases in standard space, e.g., MNI-space. This procedure allows the identification of specific brain regions. Most standard MRI software packages include a wide range of atlases but have a poor coverage of the subcortex. We estimated that approximately 7% of the known subcortical structures are mapped in standard MRI-compatible atlases [1]. Here we provide a data description of a subcortical probabilistic atlas based on ultra-high resolution in-vivo anatomical imaging using 7 T (T) MRI. The atlas includes six subcortical nuclei: the striatum (STR), the globus pallidus internal and external segment (GPi/e), the subthalamic nucleus (STN), the substantia nigra (SN), and the red nucleus (RN). These probabilistic atlases are shared on freely available platforms such as NITRC and NeuroVault and are published in NeuroImage “Quantifying inter-individual anatomical variability in the subcortex using 7 T structural MRI” [2]. PMID:26322322

  2. Changes in cortical, cerebellar and basal ganglia representation after comprehensive long term unilateral hand motor training.

    PubMed

    Walz, A D; Doppl, K; Kaza, E; Roschka, S; Platz, T; Lotze, M

    2015-02-01

    We were interested in motor performance gain after unilateral hand motor training and associated changes of cerebral and cerebellar movement representation tested with functional magnetic resonance imaging (fMRI) before and after training. Therefore, we trained the left hand of strongly right-handed healthy participants with a comprehensive training (arm ability training, AAT) over two weeks. Motor performance was tested for the trained and non-trained hand before and after the training period. Functional imaging was performed for the trained and the non-trained hand separately and comprised force modulation with the fist, sequential finger movements and a fast writing task. After the training period the performance gain of tapping movements was comparable for both hand sides, whereas the motor performance for writing showed a higher training effect for the trained hand. fMRI showed a reduction of activation in supplementary motor, dorsolateral prefrontal cortex, parietal cortical areas and lateral cerebellar areas during sequential finger movements over time. During left hand writing lateral cerebellar hemisphere also showed reduced activation, while activation of the anterior cerebellar hemisphere was increased. An initially high anterior cerebellar activation magnitude was a predictive value for high training outcome of finger tapping and visual guided movements. During the force modulation task we found increased activation in the striate. Overall, a comprehensive long-term training of the less skillful hand in healthy participants resulted in relevant motor performance improvements, as well as an intermanual learning transfer differently pronounced for the type of movement tested. Whereas cortical motor area activation decreased over time, cerebellar anterior hemisphere and striatum activity seem to represent increasing resources after long-term motor training. PMID:25194587

  3. 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

  4. Optogenetic Stimulation in a Computational Model of the Basal Ganglia Biases Action Selection and Reward Prediction Error

    PubMed Central

    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. PMID:24614169

  5. 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. PMID:24614169

  6. A pilot study of basal ganglia and thalamus structure by high dimensional mapping in children with Tourette syndrome

    PubMed Central

    Black, Kevin J.

    2013-01-01

    Background: Prior brain imaging and autopsy studies have suggested that structural abnormalities of the basal ganglia (BG) nuclei may be present in Tourette Syndrome (TS). These studies have focused mainly on the volume differences of the BG structures and not their anatomical shapes.  Shape differences of various brain structures have been demonstrated in other neuropsychiatric disorders using large-deformation, high dimensional brain mapping (HDBM-LD).  A previous study of a small sample of adult TS patients demonstrated the validity of the method, but did not find significant differences compared to controls. Since TS usually begins in childhood and adult studies may show structure differences due to adaptations, we hypothesized that differences in BG and thalamus structure geometry and volume due to etiological changes in TS might be better characterized in children. Objective: Pilot the HDBM-LD method in children and estimate effect sizes. Methods: In this pilot study, T1-weighted MRIs were collected in 13 children with TS and 16 healthy, tic-free, control children. The groups were well matched for age.  The primary outcome measures were the first 10 eigenvectors which are derived using HDBM-LD methods and represent the majority of the geometric shape of each structure, and the volumes of each structure adjusted for whole brain volume. We also compared hemispheric right/left asymmetry and estimated effect sizes for both volume and shape differences between groups. Results: We found no statistically significant differences between the TS subjects and controls in volume, shape, or right/left asymmetry.  Effect sizes were greater for shape analysis than for volume. Conclusion: This study represents one of the first efforts to study the shape as opposed to the volume of the BG in TS, but power was limited by sample size. Shape analysis by the HDBM-LD method may prove more sensitive to group differences. PMID:24715957

  7. Activity in a Cortical-Basal Ganglia Circuit for Song Is Required for Social Context-Dependent Vocal Variability

    PubMed Central

    Stepanek, Laurie

    2010-01-01

    Variability in adult motor output is important for enabling animals to respond to changing external conditions. Songbirds are useful for studying variability because they alter the amount of variation in their song depending on social context. When an adult zebra finch male sings to a female (“directed”), his song is highly stereotyped, but when he sings alone (“undirected”), his song varies across renditions. Lesions of the lateral magnocellular nucleus of the anterior nidopallium (LMAN), the output nucleus of a cortical-basal ganglia circuit for song, reduce song variability to that of the stereotyped “performance” state. However, such lesions not only eliminate LMAN's synaptic input to its targets, but can also cause structural or physiological changes in connected brain regions, and thus cannot assess whether the acute activity of LMAN is important for social modulation of adult song variability. To evaluate the effects of ongoing LMAN activity, we reversibly silenced LMAN in singing zebra finches by bilateral reverse microdialysis of the GABAA receptor agonist muscimol. We found that LMAN inactivation acutely reduced undirected song variability, both across and even within syllable renditions, to the level of directed song variability in all birds examined. Song variability returned to pre-muscimol inactivation levels after drug washout. However, unlike LMAN lesions, LMAN inactivation did not eliminate social context effects on song tempo in adult birds. These results indicate that the activity of LMAN neurons acutely and actively generates social context-dependent increases in adult song variability but that social regulation of tempo is more complex. PMID:20884763

  8. Reduced basal ganglia μ-opioid receptor availability in trigeminal neuropathic pain: A pilot study

    PubMed Central

    2012-01-01

    Background Although neuroimaging techniques have provided insights into the function of brain regions involved in Trigeminal Neuropathic Pain (TNP) in humans, there is little understanding of the molecular mechanisms affected during the course of this disorder. Understanding these processes is crucial to determine the systems involved in the development and persistence of TNP. Findings In this study, we examined the regional μ-opioid receptor (μOR) availability in vivo (non-displaceable binding potential BPND) of TNP patients with positron emission tomography (PET) using the μOR selective radioligand [11C]carfentanil. Four TNP patients and eight gender and age-matched healthy controls were examined with PET. Patients with TNP showed reduced μOR BPND in the left nucleus accumbens (NAc), an area known to be involved in pain modulation and reward/aversive behaviors. In addition, the μOR BPND in the NAc was negatively correlated with the McGill sensory and total pain ratings in the TNP patients. Conclusions Our findings give preliminary evidence that the clinical pain in TNP patients can be related to alterations in the endogenous μ-opioid system, rather than only to the peripheral pathology. The decreased availability of μORs found in TNP patients, and its inverse relationship to clinical pain levels, provide insights into the central mechanisms related to this condition. The results also expand our understanding about the impact of chronic pain on the limbic system. PMID:23006894

  9. Interacting cortical and basal ganglia networks underlying finding and tapping to the musical beat.

    PubMed

    Kung, Shu-Jen; Chen, Joyce L; Zatorre, Robert J; Penhune, Virginia B

    2013-03-01

    Humans are able to find and tap to the beat of musical rhythms varying in complexity from children's songs to modern jazz. Musical beat has no one-to-one relationship with auditory features-it is an abstract perceptual representation that emerges from the interaction between sensory cues and higher-level cognitive organization. Previous investigations have examined the neural basis of beat processing but have not tested the core phenomenon of finding and tapping to the musical beat. To test this, we used fMRI and had musicians find and tap to the beat of rhythms that varied from metrically simple to metrically complex-thus from a strong to a weak beat. Unlike most previous studies, we measured beat tapping performance during scanning and controlled for possible effects of scanner noise on beat perception. Results showed that beat finding and tapping recruited largely overlapping brain regions, including the superior temporal gyrus (STG), premotor cortex, and ventrolateral PFC (VLPFC). Beat tapping activity in STG and VLPFC was correlated with both perception and performance, suggesting that they are important for retrieving, selecting, and maintaining the musical beat. In contrast BG activity was similar in all conditions and was not correlated with either perception or production, suggesting that it may be involved in detecting auditory temporal regularity or in associating auditory stimuli with a motor response. Importantly, functional connectivity analyses showed that these systems interact, indicating that more basic sensorimotor mechanisms instantiated in the BG work in tandem with higher-order cognitive mechanisms in PFC. PMID:23163420

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

    PubMed Central

    Aravamuthan, Bhooma R.; Shoykhet, Michael

    2016-01-01

    BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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. PMID:26083760

  12. Basal ganglia dysfunction

    MedlinePlus

    ... 71. Lang AE. Parkinsonism. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ... AE. Other movement disorders. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ...

  13. Basal ganglia dysfunction

    MedlinePlus

    ... overdose Head injury Infection Liver disease Metabolic problems Multiple sclerosis Poisoning with copper, manganese, or other heavy metals ... Read More Huntington disease Movement - uncontrolled or slow Multiple sclerosis Multiple system atrophy Parkinson disease Progressive supranuclear palsy ...

  14. Intracellular pH measurements of the whole head and the basal ganglia in chronic liver disease: a phosphorus-31 MR spectroscopy study.

    PubMed

    Patel, N; Forton, D M; Coutts, G A; Thomas, H C; Taylor-Robinson, S D

    2000-09-01

    The purpose of this study was to determine the intracellular pH of the whole head and in voxels localized to the basal ganglia in patients with chronic liver disease using phosphorus-31 magnetic resonance spectroscopy (31P MRS). The study group compromised 82 patients with biopsy-proven cirrhosis (43 Child's grade A, 25 Child's grade B and 14 Child's grade C). Eleven subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, 37 showed evidence of minimal hepatic encephalopathy and 34 had overt hepatic encephalopathy. Unlocalized 31P MRS of the whole head was performed in 48 patients and 10 healthy volunteers. Localized 31P MRS of the basal ganglia was performed in the 34 patients and in 20 healthy volunteers. The intracellular pH values were calculated from the chemical shift difference between the inorganic phosphate (P) and phosphocreatine (PCr) resonances. The percentage inorganic phosphate (%Pi), phosphocreatine (%PCr) and betaNTP signals, relative to the total 31P signal, and peak area ratios of inorganic phosphate and phosphocreatine, relative to betaNTP were also measured. There were no differences between patients and volunteers in intracellular pH in 31P MR spectra measured from the whole head or the basal ganglia. There was no correlation between the severity of encephalopathy (West Haven criteria) or liver dysfunction (Child score) and intracellular pH values. There was also no significant change in the inorganic phosphate, phosphocreatine or betaNTP resonances in spectra acquired from the whole head. However, in spectra localized to the basal ganglia, there was a significant increase in mean P/NTP (p=0.02) and PCr/NTP (p=0.009). The mean %Pi and mean %PCr were also increased (p=0.06; p=0.05, respectively), but there was no significant change in mean %betaNTP. When the patient population was classified according to the severity of encephalopathy, those with overt disease had a higher mean P

  15. 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

  16. Human-specific increase of dopaminergic innervation in a striatal region associated with speech and language: A comparative analysis of the primate basal ganglia.

    PubMed

    Raghanti, Mary Ann; Edler, Melissa K; Stephenson, Alexa R; Wilson, Lakaléa J; Hopkins, William D; Ely, John J; Erwin, Joseph M; Jacobs, Bob; Hof, Patrick R; Sherwood, Chet C

    2016-07-01

    The dopaminergic innervation of the striatum has been implicated in learning processes and in the development of human speech and language. Several lines of evidence suggest that evolutionary changes in dopaminergic afferents of the striatum may be associated with uniquely human cognitive and behavioral abilities, including the association of the human-specific sequence of the FOXP2 gene with decreased dopamine in the dorsomedial striatum of mice. To examine this possibility, we quantified the density of tyrosine hydroxylase-immunoreactive axons as a measure of dopaminergic innervation within five basal ganglia regions in humans, great apes, and New and Old World monkeys. Our results indicate that humans differ from nonhuman primate species in having a significant increase in dopaminergic innervation selectively localized to the medial caudate nucleus. This region of the striatum is highly interconnected, receiving afferents from multiple neocortical regions, and supports behavioral and cognitive flexibility. The medial caudate nucleus also shows hyperactivity in humans lacking a functional FOXP2 allele and exhibits altered dopamine concentrations in humanized Foxp2 mice. Additionally, striatal dopaminergic input was not altered in chimpanzees that used socially learned attention-getting sounds versus those that did not. This evidence indicates that the increase in dopamine innervation of the medial caudate nucleus in humans is a species-typical characteristic not associated with experience-dependent plasticity. The specificity of this increase may be related to the degree of convergence from cortical areas within this region of the striatum and may also be involved in human speech and language. J. Comp. Neurol. 524:2117-2129, 2016. © 2015 Wiley Periodicals, Inc. PMID:26715195

  17. 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. PMID:25902919

  18. 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.

  19. Analysis of Small Ischemic Lesions in the Examinees of a Brain Dock and Neurological Examination of Animals Subjected to Cortical or Basal Ganglia Photothrombotic Infarction.

    PubMed

    Kuroiwa, Toshihiko; Tabata, Hitoshi; Xi, Guohua; Hua, Ya; Schallert, Timothy; Keep, Richard F

    2016-01-01

    We analyzed cases of small brain ischemic lesions found in examinees of a brain dock (neurological health screening center). Small cerebral infarction was found in 17 % of the examinees (733 cases). White matter lesions were found in 24 %. Infarctions were located in the cortex or subcortical white matter in 31 % and in the basal ganglia in 44 % of cases. Infratentorial infarction was found in 1.6 %. We have developed an animal model of small infarction in the cortex or basal ganglia induced by photothrombosis in rodents. Sprague-Dawley rats or Mongolian gerbils were anesthetized and photothrombotic infarction was induced in the left caudate nucleus or parietal cortex by light exposure via an optic fiber and intravenous Rose Bengal dye injection. Histological examination revealed development of a small spherical infarction surrounding the tip of the optic fiber. The lesion turned to a cyst by 6 weeks after lesioning. Neurological deficits were found in animals both with cortical and caudate infarction. Behavioral changes in an open field test differed with the lesion site. Neurological deficits were sustained longer in animals with larger infarctions. Thus, photothrombotic infarction is useful for analyzing location-dependent and size-dependent neurological and neuropathological changes after cerebral infarction. PMID:26463929

  20. Adaptive autoregressive identification with spectral power decomposition for studying movement-related activity in scalp EEG signals and basal ganglia local field potentials

    NASA Astrophysics Data System (ADS)

    Foffani, Guglielmo; Bianchi, Anna M.; Priori, Alberto; Baselli, Giuseppe

    2004-09-01

    We propose a method that combines adaptive autoregressive (AAR) identification and spectral power decomposition for the study of movement-related spectral changes in scalp EEG signals and basal ganglia local field potentials (LFPs). This approach introduces the concept of movement-related poles, allowing one to study not only the classical event-related desynchronizations (ERD) and synchronizations (ERS), which correspond to modulations of power, but also event-related modulations of frequency. We applied the method to analyze movement-related EEG signals and LFPs contemporarily recorded from the sensorimotor cortex, the globus pallidus internus (GPi) and the subthalamic nucleus (STN) in a patient with Parkinson's disease who underwent stereotactic neurosurgery for the implant of deep brain stimulation (DBS) electrodes. In the AAR identification we compared the whale and the exponential forgetting factors, showing that the whale forgetting provides a better disturbance rejection and it is therefore more suitable to investigate movement-related brain activity. Movement-related power modulations were consistent with previous studies. In addition, movement-related frequency modulations were observed from both scalp EEG signals and basal ganglia LFPs. The method therefore represents an effective approach to the study of movement-related brain activity.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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. PMID:27047328

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

    PubMed

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

    2013-09-01

    Atypical 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

  7. A network model of basal ganglia for understanding the roles of dopamine and serotonin in reward-punishment-risk based decision making

    PubMed Central

    Balasubramani, Pragathi P.; Chakravarthy, V. Srinivasa; Ravindran, Balaraman; Moustafa, Ahmed A.

    2015-01-01

    There is significant evidence that in addition to reward-punishment based decision making, the Basal Ganglia (BG) contributes to risk-based decision making (Balasubramani et al., 2014). Despite this evidence, little is known about the computational principles and neural correlates of risk computation in this subcortical system. We have previously proposed a reinforcement learning (RL)-based model of the BG that simulates the interactions between dopamine (DA) and serotonin (5HT) in a diverse set of experimental studies including reward, punishment and risk based decision making (Balasubramani et al., 2014). Starting with the classical idea that the activity of mesencephalic DA represents reward prediction error, the model posits that serotoninergic activity in the striatum controls risk-prediction error. Our prior model of the BG was an abstract model that did not incorporate anatomical and cellular-level data. In this work, we expand the earlier model into a detailed network model of the BG and demonstrate the joint contributions of DA-5HT in risk and reward-punishment sensitivity. At the core of the proposed network model is the following insight regarding cellular correlates of value and risk computation. Just as DA D1 receptor (D1R) expressing medium spiny neurons (MSNs) of the striatum were thought to be the neural substrates for value computation, we propose that DA D1R and D2R co-expressing MSNs are capable of computing risk. Though the existence of MSNs that co-express D1R and D2R are reported by various experimental studies, prior existing computational models did not include them. Ours is the first model that accounts for the computational possibilities of these co-expressing D1R-D2R MSNs, and describes how DA and 5HT mediate activity in these classes of neurons (D1R-, D2R-, D1R-D2R- MSNs). Starting from the assumption that 5HT modulates all MSNs, our study predicts significant modulatory effects of 5HT on D2R and co-expressing D1R-D2R MSNs which in turn

  8. Altered Neuronal Firing Pattern of the Basal Ganglia Nucleus Plays a Role in Levodopa-Induced Dyskinesia in Patients with Parkinson’s Disease

    PubMed Central

    Li, Xiaoyu; Zhuang, Ping; Li, Yongjie

    2015-01-01

    Background: Levodopa therapy alleviates the symptoms of Parkinson’s disease (PD), but long-term treatment often leads to motor complications such as levodopa-induced dyskinesia (LID). Aim: To explore the neuronal activity in the basal ganglia nuclei in patients with PD and LID. Methods: Thirty patients with idiopathic PD (age, 55.1 ± 11.0 years; disease duration, 8.7 ± 5.6 years) were enrolled between August 2006 and August 2013 at the Xuanwu Hospital, Capital Medical University, China. Their Hoehn and Yahr (1967) scores ranged from 2–4 and their UPDRS III scores were 28.5 ± 5.2. Fifteen of them had severe LID (UPDRS IV scores of 6.7 ± 1.6). Microelectrode recording was performed in the globus pallidus internus (GPi) and subthalamic nucleus (STN) during pallidotomy (n = 12) or STN deep brain stimulation (DBS; bilateral, n = 12; unilateral, n = 6). The firing patterns and frequencies of various cell types were analyzed by assessing single cell interspike intervals (ISIs) and the corresponding coefficient of variation (CV). Results: A total of 295 neurons were identified from the GPi (n = 12) and STN (n = 18). These included 26 (8.8%) highly grouped discharge, 30 (10.2%) low frequency firing, 78 (26.4%) rapid tonic discharge, 103 (34.9%) irregular activity, and 58 (19.7%) tremor-related activity. There were significant differences between the two groups (p < 0.05) for neurons with irregular firing, highly irregular cluster-like firing, and low-frequency firing. Conclusion: Altered neuronal activity was observed in the basal ganglia nucleus of GPi and STN, and may play important roles in the pathophysiology of PD and LID. PMID:26635583

  9. Fiber tractography of the axonal pathways linking the basal ganglia and cerebellum in Parkinson disease: implications for targeting in deep brain stimulation

    PubMed Central

    Sweet, Jennifer A.; Walter, Benjamin L.; Gunalan, Kabilar; Chaturvedi, Ashutosh; Mcintyre, Cameron C.; Miller, Jonathan P.

    2015-01-01

    Object 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. Methods 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. Results 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. Conclusions 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. PMID:24484226

  10. Age-Related Increases in Basal Ganglia Glutamate are Associated with TNF-Alpha, Reduced Motivation and Decreased Psychomotor Speed During IFN-alpha Treatment: Preliminary Findings

    PubMed Central

    Haroon, Ebrahim; Felger, Jennifer C.; Woolwine, Bobbi J.; Chen, Xiangchuan; Parekh, Samir; Spivey, James; Hu, Xiaoping; Miller, Andrew H.

    2014-01-01

    Inflammation-induced alterations in central nervous system (CNS) metabolism have focused on glutamate. At excessive concentrations, glutamate is toxic to glia and neurons, and inflammatory cytokines have been shown to influence glutamate metabolism by blocking glutamate reuptake and increasing glutamate release. Increased glutamate has also been found in depression, a disorder associated with increased inflammation. Data by our group have shown increased glutamate as measured by magnetic resonance spectroscopy (MRS) in basal ganglia and dorsal anterior cingulate cortex of patients administered the inflammatory cytokine interferon (IFN)-alpha. Given data that increasing age is associated with an exaggerated CNS inflammatory response, we examined whether older age (>55 years) would be associated with a greater IFN-alpha-induced increase in CNS glutamate. Using a longitudinal design, 31 patients with hepatitis C virus (HCV) underwent MRS, blood sampling for inflammatory markers, and behavioral assessments before (Visit1) and after four weeks (Visit 2) of either IFN-alpha (n=17) or no treatment (n=14). Older patients treated with IFN-alpha exhibited a significantly increased glutamate from Visit 1 to Visit 2 as reflected by the glutamate/creatine ratio (Glu/Cr) in left basal ganglia compared to older controls and younger IFN-alpha-treated and untreated subjects. In addition, increased Glu/Cr in older but not younger IFN-alpha-treated and untreated patients was associated with increased tumor necrosis factor, reduced motivation as measured by the Multidimensional Fatigue Inventory and increased choice movement time on the Cambridge Neuropsychological Test Automated Battery. Taken together, these preliminary data support the notion that older age may interact with inflammation to exaggerate the effects of inflammatory stimuli on CNS glutamate and behavior. PMID:25500218

  11. Differential gene expression for glutamic acid decarboxylase and type II calcium-calmodulin-dependent protein kinase in basal ganglia, thalamus, and hypothalamus of the monkey

    SciTech Connect

    Benson, D.L.; Isackson, P.J.; Hendry, S.H.; Jones, E.G. )

    1991-06-01

    In situ hybridization histochemistry, using cRNA probes, revealed a complementarity in the distributions of cells in the basal ganglia, basal nucleus of Meynert, thalamus, hypothalamus, and rostral part of the midbrain that showed gene expression for glutamic acid decarboxylase (GAD) or the alpha-subunit of type II calcium-calmodulin-dependent protein kinase (CAM II kinase-alpha). Cells in certain nuclei such as the thalamic reticular nucleus, globus pallidus, and pars reticulata of the substantia nigra show GAD gene expression only; others in nuclei such as the basal nucleus of Meynert, medial mamillary nuclei, and ventromedial hypothalamic nuclei show CAM II kinase-alpha gene expression only. A few nuclei, for example, the pars compacta of the substantia nigra and the greater part of the subthalamic nucleus, display gene expression for neither GAD nor CAM II kinase-alpha. In other nuclei, notably those of the dorsal thalamus, and possibly in the striatum, GAD- and CAM II kinase-expressing cells appear to form two separate populations that, in most thalamic nuclei, together account for the total cell population. In situ hybridization reveals large amounts of CAM II kinase-alpha mRNA in the neuropil of most nuclei containing CAM II kinase-alpha-positive cells, suggesting its association with dendritic polyribosomes. The message may thus be translated at those sites, close to the synapses with which the protein is associated. The in situ hybridization results, coupled with those from immunocytochemical staining for CAM II kinase-alpha protein, indicate that CAM II kinase-alpha is commonly found in certain non-GABAergic afferent fiber systems but is not necessarily present in the postsynaptic cells on which they terminate. It appears to be absent from most GABAergic fiber systems but can be present in the cells on which they terminate.

  12. A preliminary study of the frequency of anti-basal ganglia antibodies and streptococcal infection in attention deficit/hyperactivity disorder.

    PubMed

    Sanchez-Carpintero, Rocio; Albesa, Sergio Aguilera; Crespo, Nerea; Villoslada, Pablo; Narbona, Juan

    2009-07-01

    Attention deficit/hyperactivity disorder (ADHD) is often present in patients with post-streptococcal neuropsychiatric disorders such as Sydenham's chorea and PANDAS, in which anti-basal ganglia antibodies (ABGA) have been frequently found. Our study investigates the hypothesis that pharyngeal group A beta-hemolytic streptococcus (GABHS) infections and serum ABGA are more frequent in children with ADHD non-comorbid (nc-ADHD) with obsessive-compulsive disorder or tics than in controls. We compared 22 children with nc-ADHD (DSM-IV-TR) and 22 healthy controls matched by age, gender and season of sample collection, for the frequency of recent GABHS infection and the presence of ABGA. Eleven out of 22 children (51%) with nc-ADHD showed evidence of GABHS infection compared to three out of 22 (14%) controls (P = 0.007). We found positive ABGA in one ADHD subject (4%) and in one control (4%). This preliminary study indicates that frequency of ABGA in children with nc-ADHD does not differ from that in matched controls, despite the fact that our ADHD patients had had more recent GABHS infections than the controls. This suggests that ABGA do not have a role in the pathogenesis of nc-ADHD. PMID:19288046

  13. 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

  14. Projections from caudal ventrolateral prefrontal areas to brainstem preoculomotor structures and to Basal Ganglia and cerebellar oculomotor loops in the macaque.

    PubMed

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

    2015-03-01

    The caudal part of the macaque ventrolateral prefrontal (VLPF) cortex hosts several distinct areas or fields--45B, 45A, 8r, caudal 46vc, and caudal 12r--connected to the frontal eye field (area 8/FEF). To assess whether these areas/fields also display subcortical projections possibly mediating a role in controlling oculomotor behavior, we examined their descending projections, based on anterograde tracer injections in each area/field, and compared them with those of area 8/FEF. All the studied areas/fields displayed projections to brainstem preoculomotor structures, precerebellar centers, and striatal sectors that are also targets of projections originating from area 8/FEF. Specifically, these projections involved: (1) the intermediate and superficial layers of the superior colliculus; (2) the mesencephalic and pontine reticular formation; (3) the dorsomedial and lateral pontine nuclei and the reticularis tegmenti pontis; and (4) the body of the caudate nucleus. Furthermore, area 45B projected also to the regions around the trochlear nucleus and to the raphe interpositus. The present data provide evidence for a role of the caudal VLPF areas/fields in controlling oculomotor behavior not only through their connections to area 8/FEF, but also in parallel through a direct access to preoculomotor brainstem structures and to the cerebellar and basal ganglia oculomotor loops. PMID:24068552

  15. Manganese-induced atypical parkinsonism is associated with altered Basal Ganglia activity and changes in tissue levels of monoamines in the rat.

    PubMed

    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

  16. Dysprosodic Speech Following Basal Ganglia Insult: Toward a Conceptual Framework for the Study of the Cerebral Representation of Prosody

    ERIC Educational Resources Information Center

    Van Lancker Sidtis, Diana; Pachana, Nancy; Cummings, Jeffrey L.; Sidtis, John J.

    2006-01-01

    Progress in understanding brain/behavior relationships in adult-acquired dysprosody has led to models of cortical hemispheric representation of prosodic processing based on functional (linguistic vs affective) or physical (timing vs pitch) parameters. These explanatory perspectives have not been reconciled, and also a number of neurobehavior…

  17. c-Fos immunoreactivity in prefrontal, basal ganglia and limbic areas of the rat brain after central and peripheral administration of ethanol and its metabolite acetaldehyde

    PubMed Central

    Segovia, Kristen N.; Vontell, Regina; López-Cruz, Laura; Salamone, John D.; Correa, Mercè

    2013-01-01

    Considerable evidence indicates that the metabolite of ethanol (EtOH), acetaldehyde, is biologically active. Acetaldehyde can be formed from EtOH peripherally mainly by alcohol dehydrogenase (ADH), and also centrally by catalase. EtOH and acetaldehyde show differences in their behavioral effects depending upon the route of administration. In terms of their effects on motor activity and motivated behaviors, when administered peripherally acetaldehyde tends to be more potent than EtOH but shows very similar potency administered centrally. Since dopamine (DA) rich areas have an important role in regulating both motor activity and motivation, the present studies were undertaken to compare the effects of central (intraventricular, ICV) and peripheral (intraperitoneal, IP) administration of EtOH and acetaldehyde on a cellular marker of brain activity, c-Fos immunoreactivity, in DA innervated areas. Male Sprague-Dawley rats received an IP injection of vehicle, EtOH (0.5 or 2.5 g/kg) or acetaldehyde (0.1 or 0.5 g/kg) or an ICV injection of vehicle, EtOH or acetaldehyde (2.8 or 14.0 μmoles). IP administration of EtOH minimally induced c-Fos in some regions of the prefrontal cortex and basal ganglia, mainly at the low dose (0.5 g/kg), while IP acetaldehyde induced c-Fos in virtually all the structures studied at both doses. Acetaldehyde administered centrally increased c-Fos in all areas studied, a pattern that was very similar to EtOH. Thus, IP administered acetaldehyde was more efficacious than EtOH at inducing c-Fos expression. However, the general pattern of c-Fos induction promoted by ICV EtOH and acetaldehyde was similar. These results are consistent with the pattern observed in behavioral studies in which both substances produced the same magnitude of effect when injected centrally, and produced differences in potency after peripheral administration. PMID:23745109

  18. Segregation of Acetylcholine and GABA in the Rat Superior Cervical Ganglia: Functional Correlation.

    PubMed

    Elinos, Diana; Rodríguez, Raúl; Martínez, Luis Andres; Zetina, María Elena; Cifuentes, Fredy; Morales, Miguel Angel

    2016-01-01

    Sympathetic neurons have the capability to segregate their neurotransmitters (NTs) and co-transmitters to separate varicosities of single axons; furthermore, in culture, these neurons can even segregate classical transmitters. In vivo sympathetic neurons employ acetylcholine (ACh) and other classical NTs such as gamma aminobutyric acid (GABA). Herein, we explore whether these neurons in vivo segregate these classical NTs in the superior cervical ganglia of the rat. We determined the topographical distribution of GABAergic varicosities, somatic GABAA receptor, as well as the regional distribution of the segregation of ACh and GABA. We evaluated possible regional differences in efficacy of ganglionic synaptic transmission, in the sensitivity of GABAA receptor to GABA and to the competitive antagonist picrotoxin (PTX). We found that sympathetic preganglionic neurons in vivo do segregate ACh and GABA. GABAergic varicosities and GABAA receptor expression showed a rostro-caudal gradient along ganglia; in contrast, segregation exhibited a caudo-rostral gradient. These uneven regional distributions in expression of GABA, GABAA receptors, and level of segregation correlate with stronger synaptic transmission found in the caudal region. Accordingly, GABAA receptors of rostral region showed larger sensitivity to GABA and PTX. These results suggest the presence of different types of GABAA receptors in each region that result in a different regional levels of endogenous GABA inhibition. Finally, we discuss a possible correlation of these different levels of GABA modulation and the function of the target organs innervated by rostral and caudal ganglionic neurons. PMID:27092054

  19. Segregation of Acetylcholine and GABA in the Rat Superior Cervical Ganglia: Functional Correlation

    PubMed Central

    Elinos, Diana; Rodríguez, Raúl; Martínez, Luis Andres; Zetina, María Elena; Cifuentes, Fredy; Morales, Miguel Angel

    2016-01-01

    Sympathetic neurons have the capability to segregate their neurotransmitters (NTs) and co-transmitters to separate varicosities of single axons; furthermore, in culture, these neurons can even segregate classical transmitters. In vivo sympathetic neurons employ acetylcholine (ACh) and other classical NTs such as gamma aminobutyric acid (GABA). Herein, we explore whether these neurons in vivo segregate these classical NTs in the superior cervical ganglia of the rat. We determined the topographical distribution of GABAergic varicosities, somatic GABAA receptor, as well as the regional distribution of the segregation of ACh and GABA. We evaluated possible regional differences in efficacy of ganglionic synaptic transmission, in the sensitivity of GABAA receptor to GABA and to the competitive antagonist picrotoxin (PTX). We found that sympathetic preganglionic neurons in vivo do segregate ACh and GABA. GABAergic varicosities and GABAA receptor expression showed a rostro-caudal gradient along ganglia; in contrast, segregation exhibited a caudo-rostral gradient. These uneven regional distributions in expression of GABA, GABAA receptors, and level of segregation correlate with stronger synaptic transmission found in the caudal region. Accordingly, GABAA receptors of rostral region showed larger sensitivity to GABA and PTX. These results suggest the presence of different types of GABAA receptors in each region that result in a different regional levels of endogenous GABA inhibition. Finally, we discuss a possible correlation of these different levels of GABA modulation and the function of the target organs innervated by rostral and caudal ganglionic neurons. PMID:27092054

  20. Characterization and distribution of [125I]epidepride binding to dopamine D2 receptors in basal ganglia and cortex of human brain.

    PubMed

    Joyce, J N; Janowsky, A; Neve, K A

    1991-06-01

    The distribution and pharmacology of the binding of [125I]epidepride, a substituted benzamide with high affinity and selectivity for dopamine (DA) D2 receptors in rat brain (Neve et al., J. Pharmacol. Exp. Ther. 252: 1108-1116, 1990), is described in human brain. Saturation analysis of the binding of [125I]epidepride to membranes derived from striatum and regions of cortex demonstrated similar Kd values (34 and 28-33 pM, respectively) but differing maximum density of binding site values (152 and 3-8 fmol/mg of protein, respectively). The pharmacological profile of binding in cortex was also similar to striatum (epidepride greater than spiperone greater than butaclamol = flupenthixol greater than clozapine) except that an additional low-affinity site, blocked by the alpha-2 adrenergic antagonist idazoxan, was present in cortex. Quantification by autoradiography also demonstrated the greatest binding in the basal ganglia, with the striatum exhibiting greater binding than the pallidal complex or midbrain regions. For the pallidum, binding in the external segment was higher than the internal segment. Within the midbrain the binding of [125I]epidepride correlated well with the known distribution of DA-containing cell bodies, with the substantia nigra (pars compacta and pars lateralis) and ventral tegmental area (A10) higher than area A8 and central gray. Binding in frontal and parietal cortex was highest in the internal layers (layers V and VI). Temporal cortex showed a 2-fold higher density of binding than other cortical regions and a trilaminar pattern; binding was greater in the external (layers I and II) and internal layers than in the middle layers (III and IV). This pattern changed in the parahippocampal complex. Within the lateral occipitotemporal cortex, binding was densest in layers I to III and very low in layers IV to VI, but binding was almost nonexistent in the adjacent entorhinal cortex. Within the hippocampal complex, binding was evident in the subiculum

  1. Evaluation of basal ganglia and thalamic inflammation in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and tourette syndrome: a positron emission tomographic (PET) study using 11C-[R]-PK11195.

    PubMed

    Kumar, Ajay; Williams, Mitchel T; Chugani, Harry T

    2015-05-01

    We applied PET scanning with (11)C-[R]-PK11195 (PK) to evaluate neuroinflammatory changes in basal ganglia and thalamus in children with clinically diagnosed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) and Tourette syndrome. Seventeen children with PANDAS (mean age: 11.4 ± 2.6 years; 13 males), 12 with Tourette syndrome (mean age: 11.0 ± 3.0 years; 10 males), and 15 normal adults (mean age: 28.7 ± 7.9 years; 8 males) underwent dynamic PK PET imaging and binding potential, a measure of ligand-TSPO receptor (expressed by activated microglia) binding, was calculated for basal ganglia and thalamus. Binding potential values, suggesting underlying activated microglia-mediated neuroinflammation, were found to be increased in bilateral caudate and bilateral lentiform nucleus in the PANDAS group and in bilateral caudate nuclei only in the Tourette syndrome group, compared to control group. These differences in the pattern and extent of neuroinflammation also signify a possible difference in pathophysiological etiology between PANDAS and Tourette syndrome patients. PMID:25117419

  2. The role of nodose ganglia in the regulation of cardiovascular function following pulmonary exposure to ultraffine titanium dioxide

    PubMed Central

    Kan, Hong; Wu, Zhongxin; Lin, Yen-Chang; Chen, Teh-Hsun; Cumpston, Jared L; Kashon, Michael L; Leonard, Steve; Munson, Albert E; Castranova, Vincent

    2015-01-01

    The inhalation of nanosized air pollutant particles is a recognised risk factor for cardiovascular disease; however, the link between occupational exposure to engineered nanoparticles and adverse cardiovascular events remains unclear. In the present study, the authors demonstrated that pulmonary exposure of rats to ultrafine titanium dioxide (UFTiO2) significantly increased heart rate and depressed diastolic function of the heart in response to isoproterenol. Moreover, pulmonary inhalation of UFTiO2 elevated mean and diastolic blood pressure in response to norepinephrine. Pretreatment of the rats ip with the transient receptor potential (TRP) channel blocker ruthenium red inhibited substance P synthesis in nodose ganglia and associated functional and biological changes in the cardiovascular system. In conclusion, the effects of pulmonary inhalation of UFTiO2 on cardiovascular function are most likely triggered by a lung-nodose ganglia-regulated pathway via the activation of TRP channels in the lung. PMID:23593933

  3. 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. PMID:16894998

  4. Balancing on the Crest - evidence for disruption of the enteric ganglia via inappropriate lineage segregation and consequences for gastrointestinal function

    PubMed Central

    Musser, Melissa A.; Southard-Smith, E. Michelle

    2013-01-01

    Normal enteric nervous system (ENS) development relies on numerous factors, including appropriate migration, proliferation, differentiation, and maturation of neural crest (NC) derivatives. Incomplete rostral to caudal migration of enteric neural crest-derived progenitors (ENPs) down the gut is at least partially responsible for the absence of enteric ganglia that is a hallmark feature of Hirschsprung disease (HSCR). The thought that ganglia proximal to aganglionosis are normal has guided surgical procedures for HSCR patients. However, chronic gastrointestinal dysfunction suffered by a subset of patients after surgery as well as studies in HSCR mouse models suggest that aberrant NC segregation and differentiation may be occurring in ganglionated regions of the intestine. Studies in mouse models that possess enteric ganglia throughout the length of the intestine (non-HSCR) have also found that certain genetic alterations affect neural crest lineage balance and interestingly many of these mutants also have functional gastrointestinal (GI) defects. It is possible that many GI disorders can be explained in part by imbalances in NC-derived lineages. Here we review studies evaluating ENS defects in HSCR and non-HSCR mouse models, concluding with clinical implications while highlighting areas requiring further study. PMID:23376538

  5. Transcranial Magnetic Stimulation (TMS) as a Tool for Early Diagnosis and Prognostication in Cortico-Basal Ganglia Degeneration (CBD) Syndromes: Review of Literature and Case Report

    PubMed Central

    Issac, Thomas Gregor; Chandra, Sadanandavalli Retnaswami; Nagaraju, B. C.

    2016-01-01

    Background: Cortico basal degeneration (CBD) of the brain is a rare progressive neurodegenerative disease which encompasses unique neuropsychiatric manifestations. Early diagnosis is essential for initiating proper treatment and favorable outcome. Transcranial Magnetic Stimulation (TMS), a well-known technique for assessment of cortical excitatory and inhibitory properties. It was suggested that in a degenerative disease like CBD which involves the cortex as well as the subcortical structures, comparing both hemispheres, a differential pattern in TMS can be obtained which would help in early identification, prognostication and early therapeutic intervention. Case Report: We describe a case of CBD with corroborative clinical and imaging picture wherein single pulse TMS was used over both the hemispheres measuring the following parameters of interest which included: Motor Threshold (MT), Central Motor Conduction Time (CMCT) and Silent Period (SP). Results and Conclusion: Differential patterns of MT, CMCT and SP was obtained by stimulating over both the hemispheres with the affected hemisphere showing significantly reduced MT and prolonged CMCT implying early impairment of cortical and subcortical structures thereby revealing the potential application of TMS being utilized in a novel way for early detection and prognostication in CBD syndromes. PMID:27011412

  6. 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

  7. ATG12–ATG3 connects basal autophagy and late endosome function

    PubMed Central

    Murrow, Lyndsay; Debnath, Jayanta

    2015-01-01

    In addition to supporting cell survival in response to starvation or stress, autophagy promotes basal protein and organelle turnover. Compared to our understanding of stress-induced autophagy, little is known about how basal autophagy is regulated and how its activity is coordinated with other cellular processes. We recently identified a novel interaction between the ATG12–ATG3 conjugate and the ESCRT-associated protein PDCD6IP/Alix that promotes basal autophagy and endolysosomal trafficking. Moreover, ATG12–ATG3 is required for diverse PDCD6IP-mediated functions including late endosome distribution, exosome secretion, and viral budding. Our results highlight the importance of late endosomes for basal autophagic flux and reveal distinct roles for the core autophagy proteins ATG12 and ATG3 in controlling late endosome function. PMID:25998418

  8. Disentangling the Role of Cortico-Basal Ganglia Loops in Top-Down and Bottom-Up Visual Attention: An Investigation of Attention Deficits in Parkinson Disease.

    PubMed

    Tommasi, Giorgio; Fiorio, Mirta; Yelnik, Jérôme; Krack, Paul; Sala, Francesca; Schmitt, Emmanuelle; Fraix, Valérie; Bertolasi, Laura; Le Bas, Jean-François; Ricciardi, Giuseppe Kenneth; Fiaschi, Antonio; Theeuwes, Jan; Pollak, Pierre; Chelazzi, Leonardo

    2015-06-01

    It is solidly established that top-down (goal-driven) and bottom-up (stimulus-driven) attention mechanisms depend on distributed cortical networks, including prefrontal and frontoparietal regions. On the other hand, it is less clear whether the BG also contribute to one or the other of these mechanisms, or to both. The current study was principally undertaken to clarify this issue. Parkinson disease (PD), a neurodegenerative disorder primarily affecting the BG, has proven to be an effective model for investigating the contribution of the BG to different brain functions; therefore, we set out to investigate deficits of top-down and bottom-up attention in a selected cohort of PD patients. With this objective in mind, we compared the performance on three computerized tasks of two groups of 12 parkinsonian patients (assessed without any treatment), one otherwise pharmacologically treated and the other also surgically treated, with that of a group of controls. The main behavioral tool for our study was an attentional capture task, which enabled us to tap the competition between top-down and bottom-up mechanisms of visual attention. This task was suitably combined with a choice RT and a simple RT task to isolate any specific deficit of attention from deficits in motor response selection and initiation. In the two groups of patients, we found an equivalent increase of attentional capture but also comparable delays in target selection in the absence of any salient distractor (reflecting impaired top-down mechanisms) and movement initiation compared with controls. In contrast, motor response selection processes appeared to be prolonged only in the operated patients. Our results confirm that the BG are involved in both motor and cognitive domains. Specifically, damage to the BG, as it occurs in PD, leads to a distinct deficit of top-down control of visual attention, and this can account, albeit indirectly, for the enhancement of attentional capture, reflecting weakened

  9. Real-time control of hind limb functional electrical stimulation using feedback from dorsal root ganglia recordings

    NASA Astrophysics Data System (ADS)

    Bruns, Tim M.; Wagenaar, Joost B.; Bauman, Matthew J.; Gaunt, Robert A.; Weber, Douglas J.

    2013-04-01

    Objective. Functional electrical stimulation (FES) approaches often utilize an open-loop controller to drive state transitions. The addition of sensory feedback may allow for closed-loop control that can respond effectively to perturbations and muscle fatigue. Approach. We evaluated the use of natural sensory nerve signals obtained with penetrating microelectrode arrays in lumbar dorsal root ganglia (DRG) as real-time feedback for closed-loop control of FES-generated hind limb stepping in anesthetized cats. Main results. Leg position feedback was obtained in near real-time at 50 ms intervals by decoding the firing rates of more than 120 DRG neurons recorded simultaneously. Over 5 m of effective linear distance was traversed during closed-loop stepping trials in each of two cats. The controller compensated effectively for perturbations in the stepping path when DRG sensory feedback was provided. The presence of stimulation artifacts and the quality of DRG unit sorting did not significantly affect the accuracy of leg position feedback obtained from the linear decoding model as long as at least 20 DRG units were included in the model. Significance. This work demonstrates the feasibility and utility of closed-loop FES control based on natural neural sensors. Further work is needed to improve the controller and electrode technologies and to evaluate long-term viability.

  10. Real-time control of hind limb functional electrical stimulation using feedback from dorsal root ganglia recordings

    PubMed Central

    Bruns, Tim M; Wagenaar, Joost B; Bauman, Matthew J; Gaunt, Robert A; Weber, Douglas J

    2013-01-01

    Objective Functional electrical stimulation (FES) approaches often utilize an open-loop controller to drive state transitions. The addition of sensory feedback may allow for closed-loop control that can respond effectively to perturbations and muscle fatigue. Approach We evaluated the use of natural sensory nerve signals obtained with penetrating microelectrode arrays in lumbar dorsal root ganglia (DRG) as real-time feedback for closed-loop control of FES-generated hind limb stepping in anesthetized cats. Main results Leg position feedback was obtained in near real-time at 50 ms intervals by decoding the firing rates of more than 120 DRG neurons recorded simultaneously. Over 5 m of effective linear distance was traversed during closed-loop stepping trials in each of two cats. The controller compensated effectively for perturbations in the stepping path when DRG sensory feedback was provided. The presence of stimulation artifacts and the quality of DRG unit sorting did not significantly affect the accuracy of leg position feedback obtained from the linear decoding model as long as at least 20 DRG units were included in the model. Significance This work demonstrates the feasibility and utility of closed-loop FES control based on natural neural sensors. Further work is needed to improve the controller and electrode technologies and to evaluate long-term viability. PMID:23503062

  11. Basal forebrain moderates the magnitude of task-dependent amygdala functional connectivity

    PubMed Central

    Knodt, Annchen R.; Hariri, Ahmad R.

    2015-01-01

    Animal studies reveal that the amygdala promotes attention and emotional memory, in part, by driving activity in downstream target regions including the prefrontal cortex (PFC) and hippocampus. Prior work has demonstrated that the amygdala influences these regions directly through monosynaptic glutamatergic signaling, and indirectly by driving activity of the cholinergic basal forebrain and subsequent downstream acetylcholine release. Yet to date, no work has addressed the functional relevance of the cholinergic basal forebrain in facilitating signaling from the amygdala in humans. We set out to determine how blood oxygen level-dependent signal within the amygdala and cholinergic basal forebrain interact to predict neural responses within downstream targets. Here, we use functional connectivity analyses to demonstrate that the cholinergic basal forebrain moderates increased amygdala connectivity with both the PFC and the hippocampus during the processing of biologically salient stimuli in humans. We further demonstrate that functional variation within the choline transporter gene predicts the magnitude of this modulatory effect. Collectively, our results provide novel evidence for the importance of cholinergic signaling in modulating neural pathways supporting arousal, attention and memory in humans. Further, our results may shed light on prior association studies linking functional variation within the choline transporter gene and diagnoses of major depression and attention-deficit hyperactivity disorder. PMID:24847112

  12. Cranial sensory ganglia neurons require intrinsic N-cadherin function for guidance of afferent fibers to their final targets

    PubMed Central

    LaMora, Angela; Voigt, Mark M.

    2009-01-01

    Cell adhesion molecules, such as N-cadherin (cdh2), are essential for normal neuronal development, and as such have been implicated in an array of processes including neuronal differentiation and migration, and axon growth and fasciculation. Cdh2 is expressed in neurons of the peripheral nervous system during development, but its role in these cells during this time is poorly understood. Using the transgenic zebrafish line, tg(p2xr3.2:eGFPsl1), we have examined the involvement of cdh2 in the formation of sensory circuits by the peripheral nervous system. The tg(p2xr3.2:eGFPsl1) fish allows visualization of neurons comprising gV, gVII, gIX and gX and their axons throughout development. Reduction of cdh2 in this line was achieved by either crosses to the cdh2-mutant strain, glass onion (glo) or injection of a cdh2 morpholino (MO) into single-cell embryos. Here we show that cdh2 function is required to alter the directional vectors of growing axons upon reaching intermediate targets. The central axons enter the hindbrain appropriately but fail to turn caudally towards their final targets. Similarly, the peripheral axons extend ventrally, but fail to turn and project along a rostral/caudal axis. Furthermore, by expressing dominant negative cdh2 constructs selectively within cranial sensory ganglia (CSG) neurons, we found that cdh2 function is necessary within the axons to elicit these stereotypic turns, thus demonstrating that cdh2 acts cell autonomously. Together, our in vivo data reveal a novel role for cdh2 in the establishment of circuits by peripheral sensory neurons. PMID:19356698

  13. Marked Increase in Nitric Oxide Synthase mRNA in Rat Dorsal Root Ganglia after Peripheral Axotomy: In situ Hybridization and Functional Studies

    NASA Astrophysics Data System (ADS)

    Verge, Valerie M. K.; Xu, Zhang; Xu, Xiao-Jun; Wiesenfeld-Hallin, Zsuzsanna; Hokfelt, Tomas

    1992-12-01

    Using in situ hybridization, we studied nitric oxide (NO) synthase (EC 1.14.23.-) mRNA in lumbar dorsal root ganglia after peripheral transection of the sciatic nerve in rats. The effect of the NO synthase inhibitor N^ω-nitro-L-arginine methyl ester on the nociceptive flexor reflex was also studied in axotomized rats. Nerve section induced a dramatic increase in number of NO synthase mRNA-positive cells in the ipsilateral dorsal root ganglia. In some of these cells the peptides galanin and/or vasoactive intestinal polypeptide and/or neuropeptide Y were also strongly up-regulated. Intravenous administration of nitro-L-arginine methyl ester blocked spinal hyperexcitability at much lower dosages in axotomized than in normal animals. The results suggest involvement of NO in the function of lumbar sensory neurons, especially after axotomy, perhaps preferentially at peripheral sites.

  14. Analysis of basal physical fitness and lumbar muscle function according to indoor horse riding exercise.

    PubMed

    Yu, Chang Ho; Hong, Chul Un; Kang, Seung Rok; Kwon, Tae Kyu

    2014-01-01

    The aim of this study is to verify the effect of indoor horse riding exercise on basal physical exercise and lumbar muscular function. The subjects included were 20 healthy females, who participated in the horse riding exercise using SRider (Rider Co. & ChonbuK National Univ, Korea) for 30 minutes per day, 3 days per week, over a period of 8 weeks. The subjects were divided into 4 groups as follows, with 10 subjects in each group: Postural Balance Exercise mode (PBE), Abdomen Exercise mode (ADE), Whole body Exercise mode (WBE), and Multiple Exercise (MTE). Isokinetic muscular function test was performed before and after the horse riding exercise, to assess the effect of horse riding on basal physical exercise and lumbar muscular function. The test result on basal physical exercise and isokinetic muscular function showed improvements with variable degree in the back muscle strength, maximum joint torque, total work, and muscular acceleration time. The result signifies that the horse riding is an antagonistic exercise mainly performed on waist and abdomen area, and the machine induces persistent muscle contraction and causes myotonic induction enhancing the muscle strength. Indoor horse riding exercise proved its effectiveness for senior or the disabled people who need muscle exercises but have difficulties performing outdoor activities. PMID:25226940

  15. Basal enrichment within neuroepithelia suggests novel function(s) for Celsr1 protein.

    PubMed

    Formstone, Caroline J; Moxon, Christopher; Murdoch, Jennifer; Little, Peter; Mason, Ivor

    2010-07-01

    A characteristic of the 7TM-cadherins, Flamingo and Celsr1, is their asymmetric protein distribution and polarized activity at neighboring epithelial cell interfaces along defined axes of planar cell polarity. Here, we describe a novel distribution of Celsr1 protein to the basal surface of neuroepithelial cells within both the early neural tube and a less well-defined group of ventricular zone cells at the midline of the developing spinal cord. Importantly, this basal enrichment is lost in embryos homozygous for a mutant Celsr1 allele. We also demonstrate an intimate association between basal enrichment of Celsr1 protein and dorsal sensory tract morphogenesis, an intriguing spatio-temporal organization of Celsr1 protein along the apico-basal neuroepithelial axis suggestive of multiple Celsr1 protein isoforms and the existence of distinct cell surface Celsr1 protein species with direct signaling potential. Together, these data raise compelling new questions concerning the role of Celsr1 during neural development. PMID:20353824

  16. Signaling mechanisms and behavioral function of the mouse basal vomeronasal neuroepithelium

    PubMed Central

    Pérez-Gómez, Anabel; Stein, Benjamin; Leinders-Zufall, Trese; Chamero, Pablo

    2014-01-01

    The vomeronasal organ (VNO) is a sensory organ that is found in most terrestrial vertebrates and that is principally implicated in the detection of pheromones. The VNO contains specialized sensory neurons organized in a pseudostratified neuroepithelium that recognize chemical signals involved in initiating innate behavioral responses. In rodents, the VNO neuroepithelium is segregated into two distinct zones, apical and basal. The molecular mechanisms involved in ligand detection by apical and basal VNO sensory neurons differ extensively. These two VNO subsystems express different subfamilies of vomeronasal receptors and signaling molecules, detect distinct chemosignals, and project to separate regions of the accessory olfactory bulb (AOB). The roles that these olfactory subdivisions play in the control of specific olfactory-mediated behaviors are largely unclear. However, analysis of mutant mouse lines for signal transduction components together with identification of defined chemosensory ligands has revealed a fundamental role of the basal part of the mouse VNO in mediating a wide range of instinctive behaviors, such as aggression, predator avoidance, and sexual attraction. Here we will compare the divergent functions and synergies between the olfactory subsystems and consider new insights in how higher neural circuits are defined for the initiation of instinctive behaviors. PMID:25505388

  17. Yuri gagarin is required for actin, tubulin and basal body functions in Drosophila spermatogenesis.

    PubMed

    Texada, Michael J; Simonette, Rebecca A; Johnson, Cassidy B; Deery, William J; Beckingham, Kathleen M

    2008-06-01

    Males of the genus Drosophila produce sperm of remarkable length. Investigation of giant sperm production in Drosophila melanogaster has demonstrated that specialized actin and microtubule structures play key roles. The gene yuri gagarin (yuri) encodes a novel protein previously identified through its role in gravitaxis. A male-sterile mutation of yuri has revealed roles for Yuri in the functions of the actin and tubulin structures of spermatogenesis. Yuri is a component of the motile actin cones that individualize the spermatids and is essential for their formation. Furthermore, Yuri is required for actin accumulation in the dense complex, a microtubule-rich structure on the sperm nuclei thought to strengthen the nuclei during elongation. In the yuri mutant, late clusters of syncytial nuclei are deformed and disorganized. The basal bodies are also mispositioned on the nuclei, and the association of a specialized structure, the centriolar adjunct (CA), with the basal body is lost. Some of these nuclear defects might underlie a further unexpected abnormality: sperm nuclei occasionally locate to the wrong ends of the spermatid cysts. The structure of the axonemes that grow out from the basal bodies is affected in the yuri mutant, suggesting a possible role for the CA in axoneme formation. PMID:18477609

  18. Signaling mechanisms and behavioral function of the mouse basal vomeronasal neuroepithelium.

    PubMed

    Pérez-Gómez, Anabel; Stein, Benjamin; Leinders-Zufall, Trese; Chamero, Pablo

    2014-01-01

    The vomeronasal organ (VNO) is a sensory organ that is found in most terrestrial vertebrates and that is principally implicated in the detection of pheromones. The VNO contains specialized sensory neurons organized in a pseudostratified neuroepithelium that recognize chemical signals involved in initiating innate behavioral responses. In rodents, the VNO neuroepithelium is segregated into two distinct zones, apical and basal. The molecular mechanisms involved in ligand detection by apical and basal VNO sensory neurons differ extensively. These two VNO subsystems express different subfamilies of vomeronasal receptors and signaling molecules, detect distinct chemosignals, and project to separate regions of the accessory olfactory bulb (AOB). The roles that these olfactory subdivisions play in the control of specific olfactory-mediated behaviors are largely unclear. However, analysis of mutant mouse lines for signal transduction components together with identification of defined chemosensory ligands has revealed a fundamental role of the basal part of the mouse VNO in mediating a wide range of instinctive behaviors, such as aggression, predator avoidance, and sexual attraction. Here we will compare the divergent functions and synergies between the olfactory subsystems and consider new insights in how higher neural circuits are defined for the initiation of instinctive behaviors. PMID:25505388

  19. ATG12-ATG3 Interacts with Alix to Promote Basal Autophagic Flux and Late Endosome Function

    PubMed Central

    Murrow, Lyndsay; Malhotra, Ritu; Debnath, Jayanta

    2015-01-01

    The ubiquitin-like molecule ATG12 is required for the early steps of autophagy. Recently, we identified ATG3, the E2-like enzyme required for LC3 lipidation during autophagy, as an ATG12 conjugation target. Here, we demonstrate that cells lacking ATG12-ATG3 have impaired basal autophagic flux, accumulation of perinuclear late endosomes, and impaired endolysosomal trafficking. Furthermore, we identify an interaction between ATG12-ATG3 and the ESCRT-associated protein Alix (also known as PDCD6IP) and demonstrate that ATG12-ATG3 controls multiple Alix-dependent processes including late endosome distribution, exosome biogenesis, and viral budding. Lastly, similar to ATG12-ATG3, Alix is functionally required for efficient basal, but not starvation-induced, autophagy. Overall, these results identify a link between the core autophagy and ESCRT machineries and uncover a role for ATG12-ATG3 in late endosome function that is distinct from the canonical role of either ATG in autophagosome formation. PMID:25686249

  20. Zebrafish: a vertebrate tool for studying basal body biogenesis, structure, and function.

    PubMed

    Marshall, Ryan A; Osborn, Daniel P S

    2016-01-01

    Understanding the role of basal bodies (BBs) during development and disease has been largely overshadowed by research into the function of the cilium. Although these two organelles are closely associated, they have specific roles to complete for successful cellular development. Appropriate development and function of the BB are fundamental for cilia function. Indeed, there are a growing number of human genetic diseases affecting ciliary development, known collectively as the ciliopathies. Accumulating evidence suggests that BBs establish cell polarity, direct ciliogenesis, and provide docking sites for proteins required within the ciliary axoneme. Major contributions to our knowledge of BB structure and function have been provided by studies in flagellated or ciliated unicellular eukaryotic organisms, specifically Tetrahymena and Chlamydomonas. Reproducing these and other findings in vertebrates has required animal in vivo models. Zebrafish have fast become one of the primary organisms of choice for modeling vertebrate functional genetics. Rapid ex-utero development, proficient egg laying, ease of genetic manipulation, and affordability make zebrafish an attractive vertebrate research tool. Furthermore, zebrafish share over 80 % of disease causing genes with humans. In this article, we discuss the merits of using zebrafish to study BB functional genetics, review current knowledge of zebrafish BB ultrastructure and mechanisms of function, and consider the outlook for future zebrafish-based BB studies. PMID:27168933

  1. A method of basal forebrain anatomical standardization for functional image analysis.

    PubMed

    Buchsbaum, M S; Fallon, J H; Wei, T C; Guich, S; Spiegel-Cohen, J; Hamilton, M; Tang, C

    1998-12-14

    Functional as well as structural assessment of the basal forebrain has mostly focused on the dorsal caudate and putamen in axial slices where they are easily outlined or their centers located with stereotaxic methods. The more ventral extent of the basal forebrain, where the irregular form and indistinct boundaries of the nucleus accumbens and substantia innominata are difficult to trace and where the brain's ventral surface may contribute partial volume artifacts to measurement, has been less studied. We present a method based on coronal sections, landmarks placed on clearly visible anchor points, and the computational technique of thin-plate spline warping which allows the alignment of groups of individuals to common coordinates for pixel-by-pixel statistical mapping. The reliability of the landmarks across independent raters yields a median absolute difference of 1.3-1.6 mm. The validity of the method is confirmed by variance maps which reveal significant decreases in variance over spindle and bounding box alignment. PMID:10710168

  2. Molecular Cloning, Functional Characterization, and Evolutionary Analysis of Vitamin D Receptors Isolated from Basal Vertebrates

    PubMed Central

    Kollitz, Erin M.; Zhang, Guozhu; Hawkins, Mary Beth; Whitfield, G. Kerr; Reif, David M.; Kullman, Seth W.

    2015-01-01

    The vertebrate genome is a result of two rapid and successive rounds of whole genome duplication, referred to as 1R and 2R. Furthermore, teleost fish have undergone a third whole genome duplication (3R) specific to their lineage, resulting in the retention of multiple gene paralogs. The more recent 3R event in teleosts provides a unique opportunity to gain insight into how genes evolve through specific evolutionary processes. In this study we compare molecular activities of vitamin D receptors (VDR) from basal species that diverged at key points in vertebrate evolution in order to infer derived and ancestral VDR functions of teleost paralogs. Species include the sea lamprey (Petromyzon marinus), a 1R jawless fish; the little skate (Leucoraja erinacea), a cartilaginous fish that diverged after the 2R event; and the Senegal bichir (Polypterus senegalus), a primitive 2R ray-finned fish. Saturation binding assays and gel mobility shift assays demonstrate high affinity ligand binding and classic DNA binding characteristics of VDR has been conserved across vertebrate evolution. Concentration response curves in transient transfection assays reveal EC50 values in the low nanomolar range, however maximum transactivational efficacy varies significantly between receptor orthologs. Protein-protein interactions were investigated using co-transfection, mammalian 2-hybrid assays, and mutations of coregulator activation domains. We then combined these results with our previous study of VDR paralogs from 3R teleosts into a bioinformatics analysis. Our results suggest that 1, 25D3 acts as a partial agonist in basal species. Furthermore, our bioinformatics analysis suggests that functional differences between VDR orthologs and paralogs are influenced by differential protein interactions with essential coregulator proteins. We speculate that we may be observing a change in the pharmacodynamics relationship between VDR and 1, 25D3 throughout vertebrate evolution that may have been

  3. Molecular cloning, functional characterization, and evolutionary analysis of vitamin D receptors isolated from basal vertebrates.

    PubMed

    Kollitz, Erin M; Zhang, Guozhu; Hawkins, Mary Beth; Whitfield, G Kerr; Reif, David M; Kullman, Seth W

    2015-01-01

    The vertebrate genome is a result of two rapid and successive rounds of whole genome duplication, referred to as 1R and 2R. Furthermore, teleost fish have undergone a third whole genome duplication (3R) specific to their lineage, resulting in the retention of multiple gene paralogs. The more recent 3R event in teleosts provides a unique opportunity to gain insight into how genes evolve through specific evolutionary processes. In this study we compare molecular activities of vitamin D receptors (VDR) from basal species that diverged at key points in vertebrate evolution in order to infer derived and ancestral VDR functions of teleost paralogs. Species include the sea lamprey (Petromyzon marinus), a 1R jawless fish; the little skate (Leucoraja erinacea), a cartilaginous fish that diverged after the 2R event; and the Senegal bichir (Polypterus senegalus), a primitive 2R ray-finned fish. Saturation binding assays and gel mobility shift assays demonstrate high affinity ligand binding and classic DNA binding characteristics of VDR has been conserved across vertebrate evolution. Concentration response curves in transient transfection assays reveal EC50 values in the low nanomolar range, however maximum transactivational efficacy varies significantly between receptor orthologs. Protein-protein interactions were investigated using co-transfection, mammalian 2-hybrid assays, and mutations of coregulator activation domains. We then combined these results with our previous study of VDR paralogs from 3R teleosts into a bioinformatics analysis. Our results suggest that 1, 25D3 acts as a partial agonist in basal species. Furthermore, our bioinformatics analysis suggests that functional differences between VDR orthologs and paralogs are influenced by differential protein interactions with essential coregulator proteins. We speculate that we may be observing a change in the pharmacodynamics relationship between VDR and 1, 25D3 throughout vertebrate evolution that may have been

  4. Oocyte glycoproteins regulate the form and function of the follicle basal lamina and theca cells.

    PubMed

    Christensen, Alice P; Patel, Saloni H; Grasa, Patricia; Christian, Helen C; Williams, Suzannah A

    2015-05-15

    Maintaining follicle integrity during development, whereby each follicle is a functional unit containing a single oocyte, is essential for the generation of healthy oocytes. However, the mechanisms that regulate this critical function have not been determined. In this paper we investigate the role of the oocyte in maintaining follicle development. To investigate this role, we use a mouse model with oocyte-specific deletion of C1galt1 which is required for the generation of core 1-derived O-glycans. The loss of oocyte-generated O-glycans results in the joining of follicles and the generation of Multiple-Oocyte Follicles (MOFs). The aim was to determine how Mutant follicle development is modified thus enabling follicles to join. Extracellular matrix and follicle permeability were studied using histology, immunohistochemistry and electron microscopy (EM). In ovaries containing Mutant Oocytes, the Follicle basal lamina (FBL) is altered both functionally and structurally from the primary stage onwards with Mutant follicles possessing unexpectedly thicker FBL. In Mutant ovaries, the theca cell layer is also modified with intermingling of theca between adjacent follicles. MOF function was analysed but despite increased numbers of preantral MOFs in Mutants, these do not reach the preovulatory stage after gonadotrophin stimulation. We propose a model describing how oocyte initiated changes in FBL and theca cells result in follicles joining. These data reveal new and important roles for the oocyte in follicle development and follicle integrity. PMID:25557622

  5. Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit.

    PubMed

    Hatzold, Julia; Beleggia, Filippo; Herzig, Hannah; Altmüller, Janine; Nürnberg, Peter; Bloch, Wilhelm; Wollnik, Bernd; Hammerschmidt, Matthias

    2016-01-01

    The molecular pathways underlying tumor suppression are incompletely understood. Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress). Blockade of the ensuing PI3K-AKT-mTORC1-NFκB-MMP9 pathway activation in basal cells, as well as systemic isotonicity, prevents malignant transformation. Our results identify hypotonic stress as a (previously unrecognized) contributor to tumor development and establish a novel paradigm of tumor suppression. PMID:27240166

  6. Injury induces direct lineage segregation of functionally distinct airway basal stem/progenitor cell subpopulations.

    PubMed

    Pardo-Saganta, Ana; Law, Brandon M; Tata, Purushothama Rao; Villoria, Jorge; Saez, Borja; Mou, Hongmei; Zhao, Rui; Rajagopal, Jayaraj

    2015-02-01

    Following injury, stem cells restore normal tissue architecture by producing the proper number and proportions of differentiated cells. Current models of airway epithelial regeneration propose that distinct cytokeratin 8-expressing progenitor cells, arising from p63(+) basal stem cells, subsequently differentiate into secretory and ciliated cell lineages. We now show that immediately following injury, discrete subpopulations of p63(+) airway basal stem/progenitor cells themselves express Notch pathway components associated with either secretory or ciliated cell fate commitment. One basal cell population displays intracellular Notch2 activation and directly generates secretory cells; the other expresses c-myb and directly yields ciliated cells. Furthermore, disrupting Notch ligand activity within the basal cell population at large disrupts the normal pattern of lineage segregation. These non-cell-autonomous effects demonstrate that effective airway epithelial regeneration requires intercellular communication within the broader basal stem/progenitor cell population. These findings have broad implications for understanding epithelial regeneration and stem cell heterogeneity. PMID:25658372

  7. Functional characterization of the rod visual pigment of the echidna (Tachyglossus aculeatus), a basal mammal.

    PubMed

    Bickelmann, Constanze; Morrow, James M; Müller, Johannes; Chang, Belinda S W

    2012-09-01

    Monotremes are the most basal egg-laying mammals comprised of two extant genera, which are largely nocturnal. Visual pigments, the first step in the sensory transduction cascade in photoreceptors of the eye, have been examined in a variety of vertebrates, but little work has been done to study the rhodopsin of monotremes. We isolated the rhodopsin gene of the nocturnal short-beaked echidna (Tachyglossus aculeatus) and expressed and functionally characterized the protein in vitro. Three mutants were also expressed and characterized: N83D, an important site for spectral tuning and metarhodopsin kinetics, and two sites with amino acids unique to the echidna (T158A and F169A). The λ(max) of echidna rhodopsin (497.9 ± 1.1 nm) did not vary significantly in either T158A (498.0 ± 1.3 nm) or F169A (499.4 ± 0.1 nm) but was redshifted in N83D (503.8 ± 1.5 nm). Unlike other mammalian rhodopsins, echidna rhodopsin did react when exposed to hydroxylamine, although not as fast as cone opsins. The retinal release rate of light-activated echidna rhodopsin, as measured by fluorescence spectroscopy, had a half-life of 9.5 ± 2.6 min-1, which is significantly shorter than that of bovine rhodopsin. The half-life of the N83D mutant was 5.1 ± 0.1 min-1, even shorter than wild type. Our results show that with respect to hydroxylamine sensitivity and retinal release, the wild-type echidna rhodopsin displays major differences to all previously characterized mammalian rhodopsins and appears more similar to other nonmammalian vertebrate rhodopsins such as chicken and anole. However, our N83D mutagenesis results suggest that this site may mediate adaptation in the echidna to dim light environments, possibly via increased stability of light-activated intermediates. This study is the first characterization of a rhodopsin from a most basal mammal and indicates that there might be more functional variation in mammalian rhodopsins than previously assumed. PMID:22874131

  8. LRGUK-1 Is Required for Basal Body and Manchette Function during Spermatogenesis and Male Fertility

    PubMed Central

    Liu, Yan; DeBoer, Kathleen; de Kretser, David M.; O’Donnell, Liza; O’Connor, Anne E.; Merriner, D. Jo; Okuda, Hidenobu; Whittle, Belinda; Jans, David A.; Efthymiadis, Athina; McLachlan, Robert I.; Ormandy, Christopher J.; Goodnow, Chris C.; Jamsai, Duangporn; O’Bryan, Moira K.

    2015-01-01

    Male infertility affects at least 5% of reproductive age males. The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT). For the majority of OAT men a precise diagnosis cannot be provided. Here we demonstrate that leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1) is required for multiple aspects of sperm assembly, including acrosome attachment, sperm head shaping and the initiation of the axoneme growth to form the core of the sperm tail. Specifically, LRGUK-1 is required for basal body attachment to the plasma membrane, the appropriate formation of the sub-distal appendages, the extension of axoneme microtubules and for microtubule movement and organisation within the manchette. Manchette dysfunction leads to abnormal sperm head shaping. Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2. Collectively, these data establish LRGUK-1 as a major determinant of microtubule structure within the male germ line. PMID:25781171

  9. Identification, Functional Characterization, and Evolution of Terpene Synthases from a Basal Dicot.

    PubMed

    Yahyaa, Mosaab; Matsuba, Yuki; Brandt, Wolfgang; Doron-Faigenboim, Adi; Bar, Einat; McClain, Alan; Davidovich-Rikanati, Rachel; Lewinsohn, Efraim; Pichersky, Eran; Ibdah, Mwafaq

    2015-11-01

    Bay laurel (Laurus nobilis) is an agriculturally and economically important dioecious tree in the basal dicot family Lauraceae used in food and drugs and in the cosmetics industry. Bay leaves, with their abundant monoterpenes and sesquiterpenes, are used to impart flavor and aroma to food, and have also drawn attention in recent years because of their potential pharmaceutical applications. To identify terpene synthases (TPSs) involved in the production of these volatile terpenes, we performed RNA sequencing to profile the transcriptome of L. nobilis leaves. Bioinformatic analysis led to the identification of eight TPS complementary DNAs. We characterized the enzymes encoded by three of these complementary DNAs: a monoterpene synthase that belongs to the TPS-b clade catalyzes the formation of mostly 1,8-cineole; a sesquiterpene synthase belonging to the TPS-a clade catalyzes the formation of mainly cadinenes; and a diterpene synthase of the TPS-e/f clade catalyzes the formation of geranyllinalool. Comparison of the sequences of these three TPSs indicated that the TPS-a and TPS-b clades of the TPS gene family evolved early in the evolution of the angiosperm lineage, and that geranyllinalool synthase activity is the likely ancestral function in angiosperms of genes belonging to an ancient TPS-e/f subclade that diverged from the kaurene synthase gene lineages before the split of angiosperms and gymnosperms. PMID:26157114

  10. Identification, Functional Characterization, and Evolution of Terpene Synthases from a Basal Dicot1[OPEN

    PubMed Central

    Yahyaa, Mosaab; Matsuba, Yuki; Brandt, Wolfgang; Doron-Faigenboim, Adi; Bar, Einat; McClain, Alan; Davidovich-Rikanati, Rachel; Lewinsohn, Efraim; Pichersky, Eran; Ibdah, Mwafaq

    2015-01-01

    Bay laurel (Laurus nobilis) is an agriculturally and economically important dioecious tree in the basal dicot family Lauraceae used in food and drugs and in the cosmetics industry. Bay leaves, with their abundant monoterpenes and sesquiterpenes, are used to impart flavor and aroma to food, and have also drawn attention in recent years because of their potential pharmaceutical applications. To identify terpene synthases (TPSs) involved in the production of these volatile terpenes, we performed RNA sequencing to profile the transcriptome of L. nobilis leaves. Bioinformatic analysis led to the identification of eight TPS complementary DNAs. We characterized the enzymes encoded by three of these complementary DNAs: a monoterpene synthase that belongs to the TPS-b clade catalyzes the formation of mostly 1,8-cineole; a sesquiterpene synthase belonging to the TPS-a clade catalyzes the formation of mainly cadinenes; and a diterpene synthase of the TPS-e/f clade catalyzes the formation of geranyllinalool. Comparison of the sequences of these three TPSs indicated that the TPS-a and TPS-b clades of the TPS gene family evolved early in the evolution of the angiosperm lineage, and that geranyllinalool synthase activity is the likely ancestral function in angiosperms of genes belonging to an ancient TPS-e/f subclade that diverged from the kaurene synthase gene lineages before the split of angiosperms and gymnosperms. PMID:26157114

  11. Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies.

    PubMed

    Galletta, Brian J; Guillen, Rodrigo X; Fagerstrom, Carey J; Brownlee, Chris W; Lerit, Dorothy A; Megraw, Timothy L; Rogers, Gregory C; Rusan, Nasser M

    2014-09-15

    Pericentrin is a critical centrosomal protein required for organizing pericentriolar material (PCM) in mitosis. Mutations in pericentrin cause the human genetic disorder Majewski/microcephalic osteodysplastic primordial dwarfism type II, making a detailed understanding of its regulation extremely important. Germaine to pericentrin's function in organizing PCM is its ability to localize to the centrosome through the conserved C-terminal PACT domain. Here we use Drosophila pericentrin-like-protein (PLP) to understand how the PACT domain is regulated. We show that the interaction of PLP with calmodulin (CaM) at two highly conserved CaM-binding sites in the PACT domain controls the proper targeting of PLP to the centrosome. Disrupting the PLP-CaM interaction with single point mutations renders PLP inefficient in localizing to centrioles in cultured S2 cells and Drosophila neuroblasts. Although levels of PCM are unaffected, it is highly disorganized. We also demonstrate that basal body formation in the male testes and the production of functional sperm does not rely on the PLP-CaM interaction, whereas production of functional mechanosensory neurons does. PMID:25031429

  12. A general view on the reactivity of the oxygen-functionalized graphene basal plane.

    PubMed

    Dobrota, Ana S; Pašti, Igor A; Mentus, Slavko V; Skorodumova, Natalia V

    2016-03-01

    In this contribution we inspect the adsorption of H, OH, Cl and Pt on oxidized graphene using DFT calculations. The introduction of epoxy and hydroxyl groups on the graphene basal plane significantly alters its chemisorption properties, which can be attributed to the deformation of the basal plane and the type and distribution of these groups. We show that a general scaling relation exists between the hydrogen binding energies and the binding energies of other investigated adsorbates, which allows for a simple probing of the reactivity of oxidized graphene with only one adsorbate. The electronic states of carbon atoms located within the 2 eV interval below the Fermi level are found to be responsible for the interaction of the basal plane with the chosen adsorbates. The number of electronic states situated in this energy interval is shown to correlate with hydrogen binding energies. PMID:26866995

  13. Serum Basal Paraoxonase 1 Activity as an Additional Liver Function Test for the Evaluation of Patients with Chronic Hepatitis

    PubMed Central

    Halappa, Chandrakanth K; Pyati, Sudharani A; Nagaraj; Wali, Vinod

    2015-01-01

    Background The diagnostic accuracy of currently available standard panel of liver function tests is not satisfactory for the reliable diagnosis of chronic liver disorders. Earlier studies have reported that serum basal paraoxonase 1 (PON1) activity measurement may add a significant contribution to the liver function tests. Aim To assess whether the measurement of serum basal paraoxonase 1 (PON1) activity would be useful as an index of liver function status in chronic hepatitis patients. Materials and Methods The study included 50 chronic hepatitis patients and 50 apparently healthy controls based on inclusion & exclusion criteria. In all the subjects, standard liver function tests were analysed by using standard methods. Basal PON1 activity was estimated using spectrophotometric method by the hydrolysis of p-nitrophenylacetate. Student t-test, Pearson’s correlation coefficient, diagnostic validity tests and ROC curve analysis were the methods used for the statistical analysis of the data. Results The serum basal PON1 activity was significantly decreased in chronic hepatitis cases when compared to controls (p< 0.001). Also basal PON1 activity was positively correlated with serum total protein and albumin, and negatively correlated with serum total bilirubin, alanine amino transferase (ALT), and alkaline phosphatase (ALP) (p< 0.001) in chronic hepatitis cases but not in healthy controls. Diagnostic validity tests showed, basal PON1 activity was a better discriminator of chronic hepatitis than total protein, albumin and ALP with sensitivity of 68%, specificity of 100%, positive predictive value of 100% and negative predictive value of 75%. ROC curve analysis demonstrated highest diagnostic accuracy for ALT (AUC = 0.999) followed by PON1 (AUC = 0.990), total bilirubin (AUC = 0.977), ALP (AUC = 0.904), total protein (AUC = 0.790) and albumin (AUC = 0.595). Conclusion Diagnostic accuracy of serum PON1 activity is better than total bilirubin, total protein, albumin and

  14. Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit

    PubMed Central

    Hatzold, Julia; Beleggia, Filippo; Herzig, Hannah; Altmüller, Janine; Nürnberg, Peter; Bloch, Wilhelm; Wollnik, Bernd; Hammerschmidt, Matthias

    2016-01-01

    The molecular pathways underlying tumor suppression are incompletely understood. Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress). Blockade of the ensuing PI3K-AKT-mTORC1-NFκB-MMP9 pathway activation in basal cells, as well as systemic isotonicity, prevents malignant transformation. Our results identify hypotonic stress as a (previously unrecognized) contributor to tumor development and establish a novel paradigm of tumor suppression. DOI: http://dx.doi.org/10.7554/eLife.14277.001 PMID:27240166

  15. Functional up-regulation of Nav1.8 sodium channel on dorsal root ganglia neurons contributes to the induction of scorpion sting pain.

    PubMed

    Ye, Pin; Hua, Liming; Jiao, Yunlu; Li, Zhenwei; Qin, Shichao; Fu, Jin; Jiang, Feng; Liu, Tong; Ji, Yonghua

    2016-02-01

    BmK I, purified from the venom of scorpion Buthus martensi Karsch (BmK), is a receptor site-3-specific modulator of voltage-gated sodium channels (VGSCs) and can induce pain-related behaviors in rats. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 contributes to most of the sodium current underlying the action potential upstroke in dorsal root ganglia (DRG) neurons and may serve as a critical ion channel targeted by BmK I. Herein, using electrophysiological, molecular, and behavioral approaches, we investigated whether the aberrant expression of Nav1.8 in DRG contributes to generation of pain induced by BmK I. The expression of Nav1.8 was found to be significantly increased at both mRNA and protein levels following intraplantar injection of BmK I in rats. In addition, the current density of TTX-R Nav1.8 sodium channel is significantly increased and the gating kinetics of Nav1.8 is also altered in DRG neurons from BmK I-treated rats. Furthermore, spontaneous pain and mechanical allodynia, but not thermal hyperalgesia induced by BmK I, are significantly alleviated through either blockade of the Nav1.8 sodium channel by its selective blocker A-803467 or knockdown of the Nav1.8 expression in DRG by antisense oligodeoxynucleotide (AS-ODN) targeting Nav1.8 in rats. Finally, BmK I was shown to induce enhanced pain behaviors in complete freund's adjuvant (CFA)-inflamed rats, which was partly due to the over-expression of Nav1.8 in DRG. Our results suggest that functional up-regulation of Nav1.8 channel on DRG neurons contributes to the development of BmK I-induced pain in rats. PMID:26764239

  16. Pilot Study of Pioglitazone and Exercise Training Effects on Basal Myocardial Substrate Metabolism and Left Ventricular Function in HIV-Positive Individuals with Metabolic Complications

    PubMed Central

    Cade, W. Todd; Reeds, Dominic N.; Overton, E. Turner; Herrero, Pilar; Waggoner, Alan D.; Laciny, Erin; Bopp, Coco; Lassa-Claxton, Sherry; Gropler, Robert J.; Peterson, Linda R.; Yarasheski, Kevin E.

    2014-01-01

    Background Individuals with HIV infection and peripheral metabolic complications have impaired basal myocardial insulin sensitivity that is related to left ventricular (LV) diastolic dysfunction. It is unknown whether interventions shown to be effective in improving peripheral insulin sensitivity can improve basal myocardial insulin sensitivity and diastolic function in people with HIV and peripheral metabolic complications. Objective In a pilot study, we evaluated whether the peroxisome proliferator–activated receptor-gamma (PPAR-γ) agonist pioglitazone or combined endurance and resistance exercise training improves basal myocardial insulin sensitivity and diastolic function in HIV+ adults with peripheral metabolic complications. Design Twenty-four HIV+ adults with metabolic complications including peripheral insulin resistance were randomly assigned to 4 months of pioglitazone (PIO; 30 mg/d) or supervised, progressive endurance and resistance exercise training (EXS; 90–120 min/d, 3 d/wk). Basal myocardial substrate metabolism was quantified by radioisotope tracer methodology and positron emission tomography (PET) imaging, and LV function was measured by echocardiography. Results Twenty participants completed the study. Neither PIO nor EXS resulted in a detectable improvement in basal myocardial insulin sensitivity or diastolic function. Post hoc analyses revealed sample sizes of more than 100 participants are needed to detect significant effects of these interventions on basal myocardial insulin sensitivity and function. Conclusions PIO or EXS alone did not significantly increase basal myocardial insulin sensitivity or LV diastolic function in HIV+ individuals with peripheral metabolic complications. PMID:24334183

  17. [On the question of the organization of brain function: cortical associations, «disconnection» syndrome and higher brain functions].

    PubMed

    Damulin, I V

    2015-01-01

    The review considers the structural/functional brain organization, the disturbance of which is accompanied by the development of cognitive and behavioral disorders. The significance of the disruption of parallel circuits connecting frontal lobes with subcortical structures (the basal ganglia, thalamus, cerebellum) is highlighted. This disruption is clinically described as "disconnection" syndrome. The associations between the basal ganglia and the cortex of the large cerebral hemispheres responsible for motor, cognitive and emotional/behavioral functions do not restricted to these spheres and is characteristic not only of frontal brain areas. There are circuits connecting other brain compartments and the basal ganglia that provide perception, and are involved in decision making on the basis of input information of different modalities.The improvement of understanding of the pathophysiology and neurochemistry of these structures opens new possibilities for selective action on some or other circuit to achieve the best therapeutic result. PMID:26978059

  18. Dissociations in Processing Derivational Morphology: The Right Basal Ganglia Involvement

    ERIC Educational Resources Information Center

    Marangolo, Paola; Piras, Fabrizio

    2008-01-01

    In the neuropsychological literature, there is converging evidence for a dominant role of the left hemisphere in morphological processing. However, two right hemisphere patients were described with a clear dissociation between impaired derivational morphology and preserved inflectional processing. A recent fMRI experiment confirmed the involvement…

  19. RFamide peptides in agnathans and basal chordates.

    PubMed

    Osugi, Tomohiro; Son, You Lee; Ubuka, Takayoshi; Satake, Honoo; Tsutsui, Kazuyoshi

    2016-02-01

    Since a peptide with a C-terminal Arg-Phe-NH2 (RFamide peptide) was first identified in the ganglia of the venus clam in 1977, RFamide peptides have been found in the nervous system of both invertebrates and vertebrates. In vertebrates, the RFamide peptide family includes gonadotropin-inhibitory hormone (GnIH), neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP), pyroglutamylated RFamide peptide/26RFamide peptide (QRFP/26RFa), and kisspeptins (kiss1 and kiss2). They are involved in important functions such as the release of hormones, regulation of sexual or social behavior, pain transmission, reproduction, and feeding. In contrast to tetrapods and jawed fish, the information available on RFamide peptides in agnathans and basal chordates is limited, thus preventing further insights into the evolution of RFamide peptides in vertebrates. In this review, we focus on the previous research and recent advances in the studies on RFamide peptides in agnathans and basal chordates. In agnathans, the genes encoding GnIH, NPFF, and PrRP precursors and the mature peptides have been identified in lamprey (Petromyzon marinus) and hagfish (Paramyxine atami). Putative kiss1 and kiss2 genes have also been found in the genome database of lamprey. In basal chordates, namely, in amphioxus (Branchiostoma japonicum), a common ancestral form of GnIH and NPFF genes and their mature peptides, as well as the ortholog of the QRFP gene have been identified. The studies revealed that the number of orthologs of vertebrate RFamide peptides present in agnathans and basal chordates is greater than expected, suggesting that the vertebrate RFamide peptides might have emerged and expanded at an early stage of chordate evolution. PMID:26130238

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

    PubMed Central

    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 by manipulating separately the selection of sources and destinations of information transfers. We suggest that such a mechanism provides an account for several cognitive functions of the basal ganglia. The model also incorporates a possible mechanism by which subsequent transfers of information control the release of dopamine. This signal is used to produce novel stimulus–response associations by internalizing transferred cortical representations in the striatum. We discuss how the model is related to production systems and cognitive architectures. A series of simulations is presented to illustrate how the model can perform simple stimulus–response tasks, develop automatic behaviors, and provide an account of impairments in Parkinson’s and Huntington’s diseases. PMID:20438237

  1. Basal-Plane Functionalization of Chemically Exfoliated Molybdenum Disulfide by Diazonium Salts.

    PubMed

    Knirsch, Kathrin C; Berner, Nina C; Nerl, Hannah C; Cucinotta, Clotilde S; Gholamvand, Zahra; McEvoy, Niall; Wang, Zhenxing; Abramovic, Irena; Vecera, Philipp; Halik, Marcus; Sanvito, Stefano; Duesberg, Georg S; Nicolosi, Valeria; Hauke, Frank; Hirsch, Andreas; Coleman, Jonathan N; Backes, Claudia

    2015-06-23

    Although transition metal dichalcogenides such as MoS2 have been recognized as highly potent two-dimensional nanomaterials, general methods to chemically functionalize them are scarce. Herein, we demonstrate a functionalization route that results in organic groups bonded to the MoS2 surface via covalent C-S bonds. This is based on lithium intercalation, chemical exfoliation and subsequent quenching of the negative charges residing on the MoS2 by electrophiles such as diazonium salts. Typical degrees of functionalization are 10-20 atom % and are potentially tunable by the choice of intercalation conditions. Significantly, no further defects are introduced, and annealing at 350 °C restores the pristine 2H-MoS2. We show that, unlike both chemically exfoliated and pristine MoS2, the functionalized MoS2 is very well dispersible in anisole, confirming a significant modification of the surface properties by functionalization. DFT calculations show that the grafting of the functional group to the sulfur atoms of (charged) MoS2 is energetically favorable and that S-C bonds are formed. PMID:25969861

  2. Comparative analysis of basal physical fitness and muscle function in relation to muscle balance pattern using rowing machines.

    PubMed

    Kang, Seung Rok; Yu, Chang Ho; Han, Kap Soo; Kwon, Tae Kyu

    2014-01-01

    The purpose of this study was to evaluate muscle function and basal physical fitness in relation to muscle balance pattern using rowing machines. Twenty four subjects participated in this study, using three different rowing machines. Rowing exercises were performed for twenty-five times a set, four sets a day, 3 days a week, for 8 weeks. Biodex system 3(Biodex Medical Systems Co., New York, USA) was used to measure joint torques in the elbow, shoulder, lumbar and knee of subjects, for analyzing muscle function. The evaluation of basal physical fitness included body composition, muscle strength, muscle endurance, muscle reaction, agility, flexibility and explosive power. Before the experiment, significant differences of joint torques in the elbow, shoulder, lumbar and knee were present between subjects in the group. After the rowing exercise, significant improvement in every joint was witnessed. All aspects of basic fitness increased significantly, and the most improvement was observed in muscle strength from the joint torque results. As shown in the following results, every joint it was evident to have improved by more than 30% with the use of dependent load deviation type over the previously used water load method. This means that it is more effective for enhancing muscle strength and endurance to keep the muscle balance using dependent load deviation. The human body maintains motor coordination of muscle contraction during exercise. The muscle balances in the upper-lower and left-right arms could assist with effective activation of motor coordination. In this paper, an exercise method using dependent load deviation was demonstrated to be more efficient for improving muscle imbalance and strengthening muscles. PMID:25226943

  3. Intestinal inflammation caused by magnesium deficiency alters basal and oxidative stress-induced intestinal function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Magnesium-deficiency (MgD)induces a systemic pro-inflammatory state. The aim of this study was to determine the effect of MgD on the functional and molecular response to mesenteric ischemia reperfusion. Rats were assigned to 4 groups and placed on magnesium sufficient or deficient diet for 1 or 3 we...

  4. Function of bicoid and hunchback homologs in the basal cyclorrhaphan fly Megaselia (Phoridae)

    PubMed Central

    Stauber, Michael; Taubert, Heike; Schmidt-Ott, Urs

    2000-01-01

    The Drosophila gene bicoid functions at the beginning of a gene cascade that specifies anterior structures in the embryo. Its transcripts are localized at the anterior pole of the oocyte, giving rise to a Bicoid protein gradient, which regulates the spatially restricted expression of target genes along the anterior–posterior axis of the embryo in a concentration-dependent manner. The morphogen function of Bicoid requires the coactivity of the zinc finger transcription factor Hunchback, which is expressed in a Bicoid-dependent fashion in the anterior half of the embryo. Whereas hunchback is conserved throughout insects, bicoid homologs are known only from cyclorrhaphan flies. Thus far, identification of hunchback and bicoid homologs rests only on sequence comparison. In this study, we used double-stranded RNA interference (RNAi) to address the function of bicoid and hunchback homologs in embryos of the lower cyclorrhaphan fly Megaselia abdita (Phoridae). Megaselia-hunchback RNAi causes hunchback-like phenotypes as observed in Drosophila, but Megaselia-bicoid RNAi causes phenotypes different from corresponding RNAi experiments in Drosophila and bicoid mutant embryos. Megaselia-bicoid is required not only for the head and thorax but also for the development of four abdominal segments. This difference between Megaselia and Drosophila suggests that the range of functional bicoid activity has been reduced in higher flies. PMID:10995461

  5. [Effect of prednisolone on the basal gastric secretion in laboratory rats depending on functional state of the stomach adrenoreceptors].

    PubMed

    Trefilov, A B

    2002-04-01

    Activation of the stomach adrenoreceptors with adrenaline resulting in inhibition of fundal glands promotes stimulating effect of prednisolone glucocorticosteroid action on basal gastric secretion. PMID:12058541

  6. Isolation and Functional Analyses of a Putative Floral Homeotic C-Function Gene in a Basal Eudicot London Plane Tree (Platanus acerifolia)

    PubMed Central

    Liu, Guofeng; Bao, Manzhu

    2013-01-01

    The identification of mutants in model plant species has led to the isolation of the floral homeotic function genes that play crucial roles in flower organ specification. However, floral homeotic C-function genes are rarely studied in basal eudicots. Here, we report the isolation and characterization of the AGAMOUS (AG) orthologous gene (PaAG) from a basal eudicot London plane tree (Platanus acerifolia Willd). Phylogenetic analysis showed that PaAG belongs to the C- clade AG group of genes. PaAG was found to be expressed predominantly in the later developmental stages of male and female inflorescences. Ectopic expression of PaAG-1 in tobacco (Nicotiana tabacum) resulted in morphological alterations of the outer two flower whorls, as well as some defects in vegetative growth. Scanning electron micrographs (SEMs) confirmed homeotic sepal-to-carpel transformation in the transgenic plants. Protein interaction assays in yeast cells indicated that PaAG could interact directly with PaAP3 (a B-class MADS-box protein in P. acerifolia), and also PaSEP1 and PaSEP3 (E-class MADS-box proteins in P. acerifolia). This study performed the functional analysis of AG orthologous genes outside core eudicots and monocots. Our findings demonstrate a conserved functional role of AG homolog in London plane tree, which also represent a contribution towards understanding the molecular mechanisms of flower development in this monoecious tree species. PMID:23691041

  7. Isolation and functional analyses of a putative floral homeotic C-function gene in a basal eudicot London plane tree (Platanus acerifolia).

    PubMed

    Zhang, Jiaqi; Li, Zhineng; Guo, Cong; Liu, Guofeng; Bao, Manzhu

    2013-01-01

    The identification of mutants in model plant species has led to the isolation of the floral homeotic function genes that play crucial roles in flower organ specification. However, floral homeotic C-function genes are rarely studied in basal eudicots. Here, we report the isolation and characterization of the AGAMOUS (AG) orthologous gene (PaAG) from a basal eudicot London plane tree (Platanus acerifolia Willd). Phylogenetic analysis showed that PaAG belongs to the C- clade AG group of genes. PaAG was found to be expressed predominantly in the later developmental stages of male and female inflorescences. Ectopic expression of PaAG-1 in tobacco (Nicotiana tabacum) resulted in morphological alterations of the outer two flower whorls, as well as some defects in vegetative growth. Scanning electron micrographs (SEMs) confirmed homeotic sepal-to-carpel transformation in the transgenic plants. Protein interaction assays in yeast cells indicated that PaAG could interact directly with PaAP3 (a B-class MADS-box protein in P. acerifolia), and also PaSEP1 and PaSEP3 (E-class MADS-box proteins in P. acerifolia). This study performed the functional analysis of AG orthologous genes outside core eudicots and monocots. Our findings demonstrate a conserved functional role of AG homolog in London plane tree, which also represent a contribution towards understanding the molecular mechanisms of flower development in this monoecious tree species. PMID:23691041

  8. Basal Cell Carcinoma

    PubMed Central

    Lanoue, Julien

    2016-01-01

    Basal cell carcinoma is the most commonly occurring cancer in the world and overall incidence is still on the rise. While typically a slow-growing tumor for which metastases is rare, basal cell carcinoma can be locally destructive and disfiguring. Given the vast prevalence of this disease, there is a significant overall burden on patient well-being and quality of life. The current mainstay of basal cell carcinoma treatment involves surgical modalities, such as electrodessication and curettage, excision, cryosurgery, and Mohs micrographic surgery. Such methods are typically reserved for localized basal cell carcinoma and offer high five-year cure rates, but come with the risk of functional impairment, disfigurement, and scarring. Here, the authors review the evidence and indications for nonsurgical treatment modalities in cases where surgery is impractical, contraindicated, or simply not desired by the patient. PMID:27386043

  9. Basal neutrophil function in human aging: Implications in endothelial cell adhesion.

    PubMed

    Nogueira-Neto, Joes; Cardoso, André S C; Monteiro, Hugo P; Fonseca, Fernando L A; Ramos, Luiz Roberto; Junqueira, Virginia B C; Simon, Karin A

    2016-07-01

    Much attention has been drawn to the pro-inflammatory condition that accompanies aging. This study compared parameters from non-stimulated neutrophils, obtained from young (18-30 years old [y.o.]) and elderly (65-80 y.o.) human volunteers. Measured as an inflammatory marker, plasmatic concentration of hs-CRP was found higher in elderly individuals. Non-stimulated neutrophil production of ROS and NO was, respectively, 38 and 29% higher for the aged group. From the adhesion molecules evaluated, only CD11b expression was elevated in neutrophils from the aged group, whereas no differences were found for CD11a, CD18, or CD62. A 69% higher non-stimulated in vitro neutrophil/endothelial cell adhesion was observed for neutrophils isolated from elderly donors. Our results suggest that with aging, neutrophils may be constitutively producing more reactive species in closer proximity to endothelial cells of vessel walls, which may both contribute to vascular damage and reflect a neutrophil intracellular disrupted redox balance, altering neutrophil function in aging. PMID:27109745

  10. Morbidity of hand and wrist Ganglia.

    PubMed

    Tomlinson, P J; Field, J

    2006-01-01

    Pain and disability caused by ganglia of the hand and wrist were assessed using a patient-rated wrist evaluation questionnaire in 75 patients. Dorsal wrist ganglia were the most painful and disabling. However, the majority of ganglia cause little pain or disability. Consequently, referral by General Practitioners should be confined to those with pain, disability or failure of conservative management. PMID:17080521

  11. Paramecium tetraurelia basal body structure.

    PubMed

    Tassin, Anne-Marie; Lemullois, Michel; Aubusson-Fleury, Anne

    2015-01-01

    Paramecium is a free-living unicellular organism, easy to cultivate, featuring ca. 4000 motile cilia emanating from longitudinal rows of basal bodies anchored in the plasma membrane. The basal body circumferential polarity is marked by the asymmetrical organization of its associated appendages. The complex basal body plus its associated rootlets forms the kinetid. Kinetids are precisely oriented within a row in correlation with the cell polarity. Basal bodies also display a proximo-distal polarity with microtubule triplets at their proximal ends, surrounding a permanent cartwheel, and microtubule doublets at the transition zone located between the basal body and the cilium. Basal bodies remain anchored at the cell surface during the whole cell cycle. On the opposite to metazoan, there is no centriolar stage and new basal bodies develop anteriorly and at right angle from the base of the docked ones. Ciliogenesis follows a specific temporal pattern during the cell cycle and both unciliated and ciliated docked basal bodies can be observed in the same cell. The transition zone is particularly well organized with three distinct plates and a maturation of its structure is observed during the growth of the cilium. Transcriptomic and proteomic analyses have been performed in different organisms including Paramecium to understand the ciliogenesis process. The data have incremented a multi-organism database, dedicated to proteins involved in the biogenesis, composition and function of centrosomes, basal bodies or cilia. Thanks to its thousands of basal bodies and the well-known choreography of their duplication during the cell cycle, Paramecium has allowed pioneer studies focusing on the structural and functional processes underlying basal body duplication. Proteins involved in basal body anchoring are sequentially recruited to assemble the transition zone thus indicating that the anchoring process parallels the structural differentiation of the transition zone. This feature

  12. Voice and Fluency Changes as a Function of Speech Task and Deep Brain Stimulation

    ERIC Educational Resources Information Center

    Van Lancker Sidtis, Diana; Rogers, Tiffany; Godier, Violette; Tagliati, Michele; Sidtis, John J.

    2010-01-01

    Purpose: Speaking, which naturally occurs in different modes or "tasks" such as conversation and repetition, relies on intact basal ganglia nuclei. Recent studies suggest that voice and fluency parameters are differentially affected by speech task. In this study, the authors examine the effects of subcortical functionality on voice and fluency,…

  13. The Stress Model of Chronic Pain: Evidence from Basal Cortisol and Hippocampal Structure and Function in Humans

    ERIC Educational Resources Information Center

    Vachon-Presseau, Etienne; Roy, Mathieu; Martel, Marc-Olivier; Caron, Etienne; Marin, Marie-France; Chen, Jeni; Albouy, Genevieve; Plante, Isabelle; Sullivan, Michael J.; Lupien, Sonia J.; Rainville, Pierre

    2013-01-01

    Recent theories have suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor. The present study examined the associations between basal levels of cortisol collected over seven consecutive days, the hippocampal volumes and brain activation to thermal stimulations…

  14. Functional roles for the TATA promoter and enhancers in basal and Tat-induced expression of the human immunodeficiency virus type 1 long terminal repeat.

    PubMed Central

    Berkhout, B; Jeang, K T

    1992-01-01

    We have analyzed the contributory role of the human immunodeficiency virus type 1 (HIV-1) promoter and enhancers in basal and Tat-induced transcription. We found that a minimal promoter competent for basal expression is contained within sequences spanning nucleotides -43 to +80. Basal expression from this HIV-1 promoter was boosted more by the additional presence of the NF-kappa B elements than by the Sp1 elements. The minimal long terminal repeat promoter (-43 to +80), while having an intact TAR sequence, was not Tat inducible. However, the simple addition of short synthetic enhancer motifs (AP1, Oct, Sp1, and NF-kappa B) conferred Tat responsiveness. This ability to respond to Tat was in part dependent on the presence of the HIV-1 promoter. Changing the HIV-1 TATA to other eucaryotic TATA or non-TATA initiators minimally affected basal expression but altered Tat inducibility. Our findings suggest a specific context of functional promoter and enhancer elements that is optimal for Tat trans activation of the HIV-1 long terminal repeat. Our results do not allow conclusions about whether Tat acts at the level of initiation or at the level of elongation to be drawn. Images PMID:1727476

  15. Altered functional connectivity in persistent developmental stuttering.

    PubMed

    Yang, Yang; Jia, Fanlu; Siok, Wai Ting; Tan, Li Hai

    2016-01-01

    Persistent developmental stuttering (PDS) is a speech disorder that impairs communication skills. Despite extensive research, the core causes of PDS are elusive. Converging evidence from task-induced neuroimaging methods has demonstrated the contributions of the basal ganglia and the cerebellum to PDS, but such task-state neuroimaging findings are often confounded by behavioral performance differences between subjects who stutter and normal controls. Here, using resting-state functional magnetic resonance imaging, we investigated functional connectivity within cerebellar-cortical and basal ganglia-thalamocortical networks in 16 adults who stutter and 18 age-matched fluent speakers. Seed-to-voxel analysis demonstrated that, compared to controls, adults who stutter showed alternations in functional connectivity of cerebellum to motor cortex as well as connectivity among different locals within cerebellum. Additionally, we found that functional connectivity within cerebellar circuits was significantly correlated with severity of stuttering. The alternations of functional connectivity within basal ganglia-thalamocortical networks were identified as the reduced connectivity of the putamen to the superior temporal gyrus and inferior parietal lobules in adults who stutter. The abnormalities of resting state functional connectivity are assumed to affect language planning and motor execution critical for speaking fluently. Our findings may yield neurobiological cues to the biomarkers of PDS. PMID:26743821

  16. Altered functional connectivity in persistent developmental stuttering

    PubMed Central

    Yang, Yang; Jia, Fanlu; Siok, Wai Ting; Tan, Li Hai

    2016-01-01

    Persistent developmental stuttering (PDS) is a speech disorder that impairs communication skills. Despite extensive research, the core causes of PDS are elusive. Converging evidence from task-induced neuroimaging methods has demonstrated the contributions of the basal ganglia and the cerebellum to PDS, but such task-state neuroimaging findings are often confounded by behavioral performance differences between subjects who stutter and normal controls. Here, using resting-state functional magnetic resonance imaging, we investigated functional connectivity within cerebellar-cortical and basal ganglia-thalamocortical networks in 16 adults who stutter and 18 age-matched fluent speakers. Seed-to-voxel analysis demonstrated that, compared to controls, adults who stutter showed alternations in functional connectivity of cerebellum to motor cortex as well as connectivity among different locals within cerebellum. Additionally, we found that functional connectivity within cerebellar circuits was significantly correlated with severity of stuttering. The alternations of functional connectivity within basal ganglia-thalamocortical networks were identified as the reduced connectivity of the putamen to the superior temporal gyrus and inferior parietal lobules in adults who stutter. The abnormalities of resting state functional connectivity are assumed to affect language planning and motor execution critical for speaking fluently. Our findings may yield neurobiological cues to the biomarkers of PDS. PMID:26743821

  17. REGIONAL BRAIN VOLUME REDUCTIONS RELATE TO FACIAL DYSMORPHOLOGY AND NEUROCOGNITIVE FUNCTION IN FETAL ALCOHOL SPECTRUM DISORDERS

    PubMed Central

    Roussotte, Florence F.; Sulik, Kathleen K.; Mattson, Sarah N.; Riley, Edward P.; Jones, Kenneth L.; Adnams, Colleen M.; May, Philip A.; O’Connor, Mary J.; Narr, Katherine L.; Sowell, Elizabeth R.

    2013-01-01

    Individuals with heavy prenatal alcohol exposure can experience significant deficits in cognitive and psychosocial functioning and alterations in brain structure that persist into adulthood. In this report, data from 99 participants collected across three sites (Los Angeles and San Diego, California, and Cape Town, South Africa) were analyzed to examine relationships between brain structure, neurocognitive function, facial morphology, and maternal reports of quantities of alcohol consumption during the first trimester. Across study sites, we found highly significant volume reductions in the FASD group for all of the brain regions evaluated. After correcting for scan location, age, and total brain volume, these differences remained significant in some regions of the basal ganglia and diencephalon. In alcohol-exposed subjects, we found that smaller palpebral fissures were significantly associated with reduced volumes in the diencephalon bilaterally, that greater dysmorphology of the philtrum predicted smaller volumes in basal ganglia and diencephalic structures, and that lower IQ scores were associated with both smaller basal ganglia volumes and greater facial dysmorphology. In subjects from South Africa, we found a significant negative correlation between intracranial volume and total number of drinks per week in the first trimester. These results corroborate previous reports that prenatal alcohol exposure is particularly toxic to basal ganglia and diencephalic structures. We extend previous findings by illustrating relationships between specific measures of facial dysmorphology and the volumes of particular subcortical structures, and for the first time show that continuous measures of maternal alcohol consumption during the first trimester relates to overall brain volume reduction. PMID:21416562

  18. The capability to synthesize phytochelatins and the presence of constitutive and functional phytochelatin synthases are ancestral (plesiomorphic) characters for basal land plants.

    PubMed

    Petraglia, Alessandro; De Benedictis, Maria; Degola, Francesca; Pastore, Giovanni; Calcagno, Margherita; Ruotolo, Roberta; Mengoni, Alessio; Sanità di Toppi, Luigi

    2014-03-01

    Bryophytes, a paraphyletic group which includes liverworts, mosses, and hornworts, have been stated as land plants that under metal stress (particularly cadmium) do not synthesize metal-binding peptides such as phytochelatins. Moreover, very little information is available to date regarding phytochelatin synthesis in charophytes, postulated to be the direct ancestors of land plants, or in lycophytes, namely very basal tracheophytes. In this study, it was hypothesized that basal land plants and charophytes have the capability to produce phytochelatins and possess constitutive and functional phytochelatin synthases. To verify this hypothesis, twelve bryophyte species (six liverworts, four mosses, and two hornworts), three charophytes, and two lycophyte species were exposed to 0-36 μM cadmium for 72 h, and then assayed for: (i) glutathione and phytochelatin quali-quantitative content by HPLC and mass spectrometry; (ii) the presence of putative phytochelatin synthases by western blotting; and (iii) in vitro activity of phytochelatin synthases. Of all the species tested, ten produced phytochelatins in vivo, while the other seven did not. The presence of a constitutively expressed and functional phytochelatin synthase was demonstrated in all the bryophyte lineages and in the lycophyte Selaginella denticulata, but not in the charophytes. Hence, current knowledge according to phytochelatins have been stated as being absent in bryophytes was therefore confuted by this work. It is argued that the capability to synthesize phytochelatins, as well as the presence of active phytochelatin synthases, are ancestral (plesiomorphic) characters for basal land plants. PMID:24449382

  19. High Basal Activity of the PTPN22 Gain-of-Function Variant Blunts Leukocyte Responsiveness Negatively Affecting IL-10 Production in ANCA Vasculitis

    PubMed Central

    Cao, Yali; Yang, Jiajin; Colby, Kerry; Hogan, Susan L.; Hu, Yichun; Jennette, Caroline E.; Berg, Elisabeth A.; Zhang, Youkang; Jennette, J. Charles; Falk, Ronald J.; Preston, Gloria A.

    2012-01-01

    Consequences of expression of the protein tyrosine phosphatase nonreceptor 22 (PTPN22) gain-of-function variant were evaluated in leukocytes from patients with anti-neutrophil cytoplasmic autoantibody (ANCA) disease. The frequency of the gain-of-function allele within the Caucasian patient cohort was 22% (OR 1.45), compared to general American Caucasian population (16.5%, p = 0.03). Examination of the basal phosphatase activity of PTPN22 gain-of-function protein indicated persistently elevated activity in un-stimulated peripheral leukocytes, while basal activity was undetectable in leukocytes from patients without the gain-of-function variant. To examine consequences of persistently high PTPN22 activity, the activation status of ERK and p38 MAPK were analyzed. While moderate levels of activated ERK were observed in controls, it was undetectable in leukocytes expressing PTPN22 gain-of-function protein and instead p38MAPK was up-regulated. IL-10 transcription, reliant on the ERK pathway, was negatively affected. Over the course of disease, patients expressing variant PTPN22 did not show a spike in IL-10 transcription as they entered remission in contrast to controls, implying that environmentally triggered signals were blunted. Sustained activity of PTPN22, due to the gain-of-function mutation, acts as a dominant negative regulator of ERK activity leading to blunted cellular responsiveness to environmental stimuli and expression of protective cytokines. PMID:22880107

  20. Basal Cell Carcinoma (BCC)

    MedlinePlus

    ... carcinomas: Infiltrating basal cell carcinomas can be more aggressive and locally destructive than other types of basal ... to treat them early and with slightly more aggressive techniques. Excision – The basal cell carcinoma is cut ...

  1. Distinct Functional and Macrostructural Brain Changes in Parkinson’s Disease and Multiple System Atrophy

    PubMed Central

    Planetta, Peggy J.; Kurani, Ajay S.; Shukla, Priyank; Prodoehl, Janey; Corcos, Daniel M.; Comella, Cynthia L.; McFarland, Nikolaus R.; Okun, Michael S.; Vaillancourt, David E.

    2016-01-01

    Parkinson’s disease (PD) and the parkinsonian variant of multiple system atrophy (MSAp) are neurodegenerative disorders that can be difficult to differentiate clinically. This study provides the first characterization of the patterns of task-related functional magnetic resonance imaging (fMRI) changes across the whole brain in MSAp. We used fMRI during a precision grip force task and also performed voxel-based morphometry (VBM) on T1-weighted images in MSAp patients, PD patients, and healthy controls. All groups were matched on age, and the patient groups had comparable motor symptom durations and severities. There were three main findings. First, MSAp and PD had reduced fMRI activation in motor control areas, including the basal ganglia, thalamus, insula, primary sensorimotor and prefrontal cortices, and cerebellum compared with controls. Second, there were no activation differences among the disease groups in the basal ganglia, thalamus, insula, or primary sensorimotor cortices, but PD had more extensive activation deficits throughout the cerebrum compared with MSAp and controls. Third, VBM revealed reduced volume in the basal ganglia, middle and inferior cerebellar peduncles, pons, and throughout the cerebrum in MSAp compared with controls and PD, and additionally throughout the cerebellar cortex and vermis in MSAp compared with controls. Collectively, these results provide the first evidence that fMRI activation is abnormal in the basal ganglia, cerebellum, and cerebrum in MSAp, and that a key distinguishing feature between MSAp and PD is the extensive and widespread volume loss throughout the brain in MSAp. PMID:25413603

  2. Distinct functional and macrostructural brain changes in Parkinson's disease and multiple system atrophy.

    PubMed

    Planetta, Peggy J; Kurani, Ajay S; Shukla, Priyank; Prodoehl, Janey; Corcos, Daniel M; Comella, Cynthia L; McFarland, Nikolaus R; Okun, Michael S; Vaillancourt, David E

    2015-03-01

    Parkinson's disease (PD) and the parkinsonian variant of multiple system atrophy (MSAp) are neurodegenerative disorders that can be difficult to differentiate clinically. This study provides the first characterization of the patterns of task-related functional magnetic resonance imaging (fMRI) changes across the whole brain in MSAp. We used fMRI during a precision grip force task and also performed voxel-based morphometry (VBM) on T1 -weighted images in MSAp patients, PD patients, and healthy controls. All groups were matched on age, and the patient groups had comparable motor symptom durations and severities. There were three main findings. First, MSAp and PD had reduced fMRI activation in motor control areas, including the basal ganglia, thalamus, insula, primary sensorimotor and prefrontal cortices, and cerebellum compared with controls. Second, there were no activation differences among the disease groups in the basal ganglia, thalamus, insula, or primary sensorimotor cortices, but PD had more extensive activation deficits throughout the cerebrum compared with MSAp and controls. Third, VBM revealed reduced volume in the basal ganglia, middle and inferior cerebellar peduncles, pons, and throughout the cerebrum in MSAp compared with controls and PD, and additionally throughout the cerebellar cortex and vermis in MSAp compared with controls. Collectively, these results provide the first evidence that fMRI activation is abnormal in the basal ganglia, cerebellum, and cerebrum in MSAp, and that a key distinguishing feature between MSAp and PD is the extensive and widespread volume loss throughout the brain in MSAp. PMID:25413603

  3. 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

  4. Selective extracellular stimulation of individual neurons in ganglia

    NASA Astrophysics Data System (ADS)

    Lu, Hui; Chestek, Cynthia A.; Shaw, Kendrick M.; Chiel, Hillel J.

    2008-09-01

    Selective control of individual neurons could clarify neural functions and aid disease treatments. To target specific neurons, it may be useful to focus on ganglionic neuron clusters, which are found in the peripheral nervous system in vertebrates. Because neuron cell bodies are found primarily near the surface of invertebrate ganglia, and often found near the surface of vertebrate ganglia, we developed a technique for controlling individual neurons extracellularly using the buccal ganglia of the marine mollusc Aplysia californica as a model system. We experimentally demonstrated that anodic currents can selectively activate an individual neuron and cathodic currents can selectively inhibit an individual neuron using this technique. To define spatial specificity, we studied the minimum currents required for stimulation, and to define temporal specificity, we controlled firing frequencies up to 45 Hz. To understand the mechanisms of spatial and temporal specificity, we created models using the NEURON software package. To broadly predict the spatial specificity of arbitrary neurons in any ganglion sharing similar geometry, we created a steady-state analytical model. A NEURON model based on cat spinal motor neurons showed responses to extracellular stimulation qualitatively similar to those of the Aplysia NEURON model, suggesting that this technique could be widely applicable to vertebrate and human peripheral ganglia having similar geometry.

  5. Long-Term Activation of Group I Metabotropic Glutamate Receptors Increases Functional TRPV1-Expressing Neurons in Mouse Dorsal Root Ganglia

    PubMed Central

    Masuoka, Takayoshi; Kudo, Makiko; Yoshida, Junko; Ishibashi, Takaharu; Muramatsu, Ikunobu; Kato, Nobuo; Imaizumi, Noriko; Nishio, Matomo

    2016-01-01

    Damaged tissues release glutamate and other chemical mediators for several hours. These chemical mediators contribute to modulation of pruritus and pain. Herein, we investigated the effects of long-term activation of excitatory glutamate receptors on functional expression of transient receptor potential vaniloid type 1 (TRPV1) in dorsal root ganglion (DRG) neurons and then on thermal pain behavior. In order to detect the TRPV1-mediated responses in cultured DRG neurons, we monitored intracellular calcium responses to capsaicin, a TRPV1 agonist, with Fura-2. Long-term (4 h) treatment with glutamate receptor agonists (glutamate, quisqualate or DHPG) increased the proportion of neurons responding to capsaicin through activation of metabotropic glutamate receptor mGluR1, and only partially through the activation of mGluR5; engagement of these receptors was evident in neurons responding to allylisothiocyanate (AITC), a transient receptor potential ankyrin type 1 (TRPA1) agonist. Increase in the proportion was suppressed by phospholipase C (PLC), protein kinase C, mitogen/extracellular signal-regulated kinase, p38 mitogen-activated protein kinase or transcription inhibitors. Whole-cell recording was performed to record TRPV1-mediated membrane current; TRPV1 current density significantly increased in the AITC-sensitive neurons after the quisqualate treatment. To elucidate the physiological significance of this phenomenon, a hot plate test was performed. Intraplantar injection of quisqualate or DHPG induced heat hyperalgesia that lasted for 4 h post injection. This chronic hyperalgesia was attenuated by treatment with either mGluR1 or mGluR5 antagonists. These results suggest that long-term activation of mGluR1/5 by peripherally released glutamate may increase the number of neurons expressing functional TRPV1 in DRG, which may be strongly associated with chronic hyperalgesia. PMID:27064319

  6. Long-Term Activation of Group I Metabotropic Glutamate Receptors Increases Functional TRPV1-Expressing Neurons in Mouse Dorsal Root Ganglia.

    PubMed

    Masuoka, Takayoshi; Kudo, Makiko; Yoshida, Junko; Ishibashi, Takaharu; Muramatsu, Ikunobu; Kato, Nobuo; Imaizumi, Noriko; Nishio, Matomo

    2016-01-01

    Damaged tissues release glutamate and other chemical mediators for several hours. These chemical mediators contribute to modulation of pruritus and pain. Herein, we investigated the effects of long-term activation of excitatory glutamate receptors on functional expression of transient receptor potential vaniloid type 1 (TRPV1) in dorsal root ganglion (DRG) neurons and then on thermal pain behavior. In order to detect the TRPV1-mediated responses in cultured DRG neurons, we monitored intracellular calcium responses to capsaicin, a TRPV1 agonist, with Fura-2. Long-term (4 h) treatment with glutamate receptor agonists (glutamate, quisqualate or DHPG) increased the proportion of neurons responding to capsaicin through activation of metabotropic glutamate receptor mGluR1, and only partially through the activation of mGluR5; engagement of these receptors was evident in neurons responding to allylisothiocyanate (AITC), a transient receptor potential ankyrin type 1 (TRPA1) agonist. Increase in the proportion was suppressed by phospholipase C (PLC), protein kinase C, mitogen/extracellular signal-regulated kinase, p38 mitogen-activated protein kinase or transcription inhibitors. Whole-cell recording was performed to record TRPV1-mediated membrane current; TRPV1 current density significantly increased in the AITC-sensitive neurons after the quisqualate treatment. To elucidate the physiological significance of this phenomenon, a hot plate test was performed. Intraplantar injection of quisqualate or DHPG induced heat hyperalgesia that lasted for 4 h post injection. This chronic hyperalgesia was attenuated by treatment with either mGluR1 or mGluR5 antagonists. These results suggest that long-term activation of mGluR1/5 by peripherally released glutamate may increase the number of neurons expressing functional TRPV1 in DRG, which may be strongly associated with chronic hyperalgesia. PMID:27064319

  7. Expression and function of calcitonin gene-related peptide (CGRP) receptors in trigeminal ganglia of R192Q Cacna1a knock-in mice.

    PubMed

    Vilotti, Sandra; Vana, Natascha; Van den Maagdenberg, Arn M J M; Nistri, Andrea

    2016-05-01

    Migraine is a neurovascular brain disorder suggested to be due to dysfunction of the trigeminovascular system with sensitization of trigeminal ganglion (TG) nociceptors. Since the neuropeptide calcitonin gene-related peptide (CGRP) has been established as a key player in the pathogenesis of migraine, CGRP receptor antagonists have been considered useful compounds to block headache originating from hyperactivation of such TG neurons. Whereas there is some information on the expression of CGRP receptors in postmortem human tissue, data are lacking for migraineurs suffering from common or genetic migraine. To help to clarify these issues it is very useful to study a transgenic knock-in (KI) mouse model of hemiplegic migraine expressing a R192Q missense mutation in the α1 subunit of CaV2.1 calcium channels previously found in patients with familial hemiplegic migraine type-1 (FHM-1). The aim of the present study, therefore, was to compare CGRP receptor expression and function in wildtype (WT) versus KI mouse TG. The principal components of the CGRP receptor, namely the CLR and RAMP-1 proteins, were similarly expressed in WT and KI TG neurons (in situ or in culture) and responded to exogenous CGRP with a strong rise in cAMP concentration. Hence, the previously reported phenotype of sensitization of KI TG neurons is not due to up-regulation of CGRP receptors but is likely caused by a constitutively larger release of CGRP. This observation implies that, in FHM-1 TG, normal TG sensory neuron signaling can be restored once the extracellular concentration of CGRP returns to control level with targeted treatment. PMID:27021026

  8. Human basal body basics.

    PubMed

    Vertii, Anastassiia; Hung, Hui-Fang; Hehnly, Heidi; Doxsey, Stephen

    2016-01-01

    In human cells, the basal body (BB) core comprises a ninefold microtubule-triplet cylindrical structure. Distal and subdistal appendages are located at the distal end of BB, where they play indispensable roles in cilium formation and function. Most cells that arrest in the G0 stage of the cell cycle initiate BB docking at the plasma membrane followed by BB-mediated growth of a solitary primary cilium, a structure required for sensing the extracellular environment and cell signaling. In addition to the primary cilium, motile cilia are present in specialized cells, such as sperm and airway epithelium. Mutations that affect BB function result in cilia dysfunction. This can generate syndromic disorders, collectively called ciliopathies, for which there are no effective treatments. In this review, we focus on the features and functions of BBs and centrosomes in Homo sapiens. PMID:26981235

  9. Adeno-associated virus type 2 rep gene-mediated inhibition of basal gene expression of human immunodeficiency virus type 1 involves its negative regulatory functions.

    PubMed Central

    Oelze, I; Rittner, K; Sczakiel, G

    1994-01-01

    Adeno-associated virus type 2 (AAV-2), a human parvovirus which is apathogenic in adults, inhibits replication and gene expression of human immunodeficiency virus type 1 (HIV-1) in human cells. The rep gene of AAV-2, which was shown earlier to be sufficient for this negative interference, also down-regulated the expression of heterologous sequences driven by the long terminal repeat (LTR) of HIV-1. This effect was observed in the absence of the HIV-1 transactivator Tat, i.e., at basal levels of LTR-driven transcription. In this work, we studied the involvement of functional subsequences of the HIV-1 LTR in rep-mediated inhibition in the absence of Tat. Mutated LTRs driving an indicator gene (cat) were cointroduced into human SW480 cells together with rep alone or with double-stranded DNA fragments or RNA containing sequences of the HIV-1 LTR. The results indicate that rep strongly enhances the function of negative regulatory elements of the LTR. In addition, the experiments revealed a transcribed sequence element located within the TAR-coding sequence termed AHHH (AAV-HIV homology element derived from HIV-1) which is involved in rep-mediated inhibition. The AHHH element is also involved in down-regulation of basal expression levels in the absence of rep, suggesting that AHHH also contributes to negative regulatory functions of the LTR of HIV-1. In contrast, positive regulatory elements of the HIV-1 LTR such as the NF kappa B and SP1 binding sites have no significant influence on the rep-mediated inhibition. Images PMID:8289357

  10. ID4 controls luminal lineage commitment in normal mammary epithelium and inhibits BRCA1 function in basal-like breast cancer.

    PubMed

    Baker, Laura A; Holliday, Holly; Swarbrick, Alexander

    2016-09-01

    Inhibitor of differentiation (ID) proteins are key regulators of development and tumorigenesis. One member of this family, ID4, controls lineage commitment during mammary gland development by acting upstream of key developmental pathways. Recent evidence suggests an emerging role for ID4 as a lineage-dependent proto-oncogene that is overexpressed and amplified in a subset of basal-like breast cancers (BLBCs), conferring poor prognosis. Several lines of evidence suggest ID4 may suppress BRCA1 function in BLBC and in doing so, define a subset of BLBC patients who may respond to therapies traditionally used in BRCA1-mutant cancers. This review highlights recent advances in our understanding of the requirement for ID4 in mammary lineage commitment and the role for ID4 in BLBC. We address current shortfalls in this field and identify important areas of future research. PMID:27412917

  11. Novel role of Engrailed 1 as a prosurvival transcription factor in basal-like breast cancer and engineering of interference peptides block its oncogenic function

    PubMed Central

    Beltran, A S; Graves, L M; Blancafort, P

    2014-01-01

    Basal-like breast tumors are aggressive cancers associated with high proliferation and metastasis. Chemotherapy is currently the only treatment option; however, resistance often occurs resulting in recurrence and patient death. Some extremely aggressive cancers are also associated with hypoxia, inflammation and high leukocyte infiltration. Herein, we discovered that the neural-specific transcription factor, Engrailed 1 (EN1), is exclusively overexpressed in these tumors. Short hairpin RNA (shRNA)-mediated knockdown of EN1 triggered potent and selective cell death. In contrast, ectopic overexpression of EN1 in normal cells activated survival pathways and conferred resistance to chemotherapeutic agents. Exogenous expression of EN1 cDNA reprogrammed the breast epithelial cells toward a long-lived, neural-like phenotype displaying dopaminergic markers. Gene expression microarrays demonstrated that the EN1 cDNA altered transcription of a high number of inflammatory molecules, notably chemokines and chemokine receptors, which could mediate prosurvival pathways. To block EN1 function, we engineered synthetic interference peptides (iPeps) comprising the EN1-specific sequences that mediate essential protein-protein interactions necessary for EN1 function and an N-terminal cell-penetrating peptide/nuclear localization sequence. These EN1-iPeps rapidly mediated a strong apoptotic response in tumor cells overexpressing EN1, with no toxicity to normal or non EN1-expressing cells. Delivery of EN1-iPeps into basal-like cancer cells significantly decreased the fifty percent inhibitory concentrations (IC50) of chemotherapeutic drugs routinely used to treat breast cancer. Lastly, matrix-assisted laser desorption/ionization-time of flight mass spectrometry and immunoprecipitation assays demonstrated that EN1-iPeps captured targets involved in transcriptional and post-transcriptional regulation. Importantly, the EN1-iPeps bound the glutamyl-prolyl tRNA synthetase (EPRS) target, which

  12. Synaptic dimorphism in Onychophoran cephalic ganglia.

    PubMed

    Peña-Contreras, Z; Mendoza-Briceño, R V; Miranda-Contreras, L; Palacios-Prü, E L

    2007-03-01

    The taxonomic location of the Onychophora has been controversial because of their phenotypic and genotypic characteristics, related to both annelids and arthropods. We analyzed the ultrastructure of the neurons and their synapses in the cephalic ganglion of a poorly known invertebrate, the velvet worm Peripatus sedgwicki, from the mountainous region of El Valle, Mérida, Venezuela. Cephalic ganglia were dissected, fixed and processed for transmission electron microscopy. The animal has a high degree of neurobiological development, as evidenced by the presence of asymmetric (excitatory) and symmetric (inhibitory) synapses, as well as the existence of glial cell processes in a wide neuropile zone. The postsynaptic terminals were seen to contain subsynaptic cisterns formed by membranes of smooth endoplasmic reticulum beneath the postsynaptic density, whereas the presynaptic terminal showed numerous electron transparent synaptic vesicles. From the neurophylogenetic perspectives, the ultrastructural characteristics of the central nervous tissue of the Onychophora show important evolutionary acquirements, such as the presence of both excitatory and inhibitory synapses, indicating functional synaptic transmission, and the appearance of mature glial cells. PMID:18457135

  13. Motor network structure and function are associated with motor performance in Huntington's disease.

    PubMed

    Müller, Hans-Peter; Gorges, Martin; Grön, Georg; Kassubek, Jan; Landwehrmeyer, G Bernhard; Süßmuth, Sigurd D; Wolf, Robert Christian; Orth, Michael

    2016-03-01

    In Huntington's disease, the relationship of brain structure, brain function and clinical measures remains incompletely understood. We asked how sensory-motor network brain structure and neural activity relate to each other and to motor performance. Thirty-four early stage HD and 32 age- and sex-matched healthy control participants underwent structural magnetic resonance imaging (MRI), diffusion tensor, and intrinsic functional connectivity MRI. Diffusivity patterns were assessed in the cortico-spinal tract and the thalamus-somatosensory cortex tract. For the motor network connectivity analyses the dominant M1 motor cortex region and for the basal ganglia-thalamic network the thalamus were used as seeds. Region to region structural and functional connectivity was examined between thalamus and somatosensory cortex. Fractional anisotropy (FA) was higher in HD than controls in the basal ganglia, and lower in the external and internal capsule, in the thalamus, and in subcortical white matter. Between-group axial and radial diffusivity differences were more prominent than differences in FA, and correlated with motor performance. Within the motor network, the insula was less connected in HD than in controls, with the degree of connection correlating with motor scores. The basal ganglia-thalamic network's connectivity differed in the insula and basal ganglia. Tract specific white matter diffusivity and functional connectivity were not correlated. In HD sensory-motor white matter organization and functional connectivity in a motor network were independently associated with motor performance. The lack of tract-specific association of structure and function suggests that functional adaptation to structural loss differs between participants. PMID:26762394

  14. The basal function of teleost prolactin as a key regulator on ion uptake identified with zebrafish knockout models

    PubMed Central

    Shu, Yuqin; Lou, Qiyong; Dai, Ziru; Dai, Xiangyan; He, Jiangyan; Hu, Wei; Yin, Zhan

    2016-01-01

    Prolactin (PRL) is an anterior pituitary hormone with a broad range of functions. Its ability to stimulate lactogenesis, maternal behavior, growth and development, osmoregulation, and epithelial ion transport has been reported in many vertebrates. In our present study, we have targeted the zebrafish prl locus via transcription activator-like effector nucleases (TALENs). Two independent targeted mutant lines with premature termination of the putative sequence of PRL peptides were generated. All prl-deficient zebrafish progeny died at 6–16 days post-fertilization stage (dpf) in egg water. However, the prl-deficient larvae thrived and survived through adulthood in brackish water (5175 mg/L ocean salts), without obvious defects in somatic growth or reproduction. When raised in egg water, the expression levels of certain key Na+/Cl− cotransporters in the gills and Na+/K+-ATPase subunits, Na+/H+ exchangers and Na+/Cl− transporters in the pronephros of prl-deficient larvae were down-regulated at 5 dpf, which caused Na+/K+/Cl− uptake defects in the mutant fish at 6 dpf. Our present results demonstrate that the primary function of zebrafish prl is osmoregulation via governing the uptake and homeostasis of Na+, K+ and Cl−. Our study provides valuable evidence to understand the mechanisms of PRL function better through both phylogenetic and physiological perspectives. PMID:26726070

  15. The basal function of teleost prolactin as a key regulator on ion uptake identified with zebrafish knockout models.

    PubMed

    Shu, Yuqin; Lou, Qiyong; Dai, Ziru; Dai, Xiangyan; He, Jiangyan; Hu, Wei; Yin, Zhan

    2016-01-01

    Prolactin (PRL) is an anterior pituitary hormone with a broad range of functions. Its ability to stimulate lactogenesis, maternal behavior, growth and development, osmoregulation, and epithelial ion transport has been reported in many vertebrates. In our present study, we have targeted the zebrafish prl locus via transcription activator-like effector nucleases (TALENs). Two independent targeted mutant lines with premature termination of the putative sequence of PRL peptides were generated. All prl-deficient zebrafish progeny died at 6-16 days post-fertilization stage (dpf) in egg water. However, the prl-deficient larvae thrived and survived through adulthood in brackish water (5175 mg/L ocean salts), without obvious defects in somatic growth or reproduction. When raised in egg water, the expression levels of certain key Na(+)/Cl(-) cotransporters in the gills and Na(+)/K(+)-ATPase subunits, Na(+)/H(+) exchangers and Na(+)/Cl(-) transporters in the pronephros of prl-deficient larvae were down-regulated at 5 dpf, which caused Na(+)/K(+)/Cl(-) uptake defects in the mutant fish at 6 dpf. Our present results demonstrate that the primary function of zebrafish prl is osmoregulation via governing the uptake and homeostasis of Na(+), K(+) and Cl(-). Our study provides valuable evidence to understand the mechanisms of PRL function better through both phylogenetic and physiological perspectives. PMID:26726070

  16. 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

  17. Multiple roles for keratin intermediate filaments in the regulation of epithelial barrier function and apico-basal polarity

    PubMed Central

    Salas, Pedro J.; Forteza, Radia; Mashukova, Anastasia

    2016-01-01

    abstract As multicellular organisms evolved a family of cytoskeletal proteins, the keratins (types I and II) expressed in epithelial cells diversified in more than 20 genes in vertebrates. There is no question that keratin filaments confer mechanical stiffness to cells. However, such a number of genes can hardly be explained by evolutionary advantages in mechanical features. The use of transgenic mouse models has revealed unexpected functional relationships between keratin intermediate filaments and intracellular signaling. Accordingly, loss of keratins or mutations in keratins that cause or predispose to human diseases, result in increased sensitivity to apoptosis, regulation of innate immunity, permeabilization of tight junctions, and mistargeting of apical proteins in different epithelia. Precise mechanistic explanations for these phenomena are still lacking. However, immobilization of membrane or cytoplasmic proteins, including chaperones, on intermediate filaments (“scaffolding”) appear as common molecular mechanisms and may explain the need for so many different keratin genes in vertebrates. PMID:27583190

  18. Multiple roles for keratin intermediate filaments in the regulation of epithelial barrier function and apico-basal polarity.

    PubMed

    Salas, Pedro J; Forteza, Radia; Mashukova, Anastasia

    2016-01-01

    As multicellular organisms evolved a family of cytoskeletal proteins, the keratins (types I and II) expressed in epithelial cells diversified in more than 20 genes in vertebrates. There is no question that keratin filaments confer mechanical stiffness to cells. However, such a number of genes can hardly be explained by evolutionary advantages in mechanical features. The use of transgenic mouse models has revealed unexpected functional relationships between keratin intermediate filaments and intracellular signaling. Accordingly, loss of keratins or mutations in keratins that cause or predispose to human diseases, result in increased sensitivity to apoptosis, regulation of innate immunity, permeabilization of tight junctions, and mistargeting of apical proteins in different epithelia. Precise mechanistic explanations for these phenomena are still lacking. However, immobilization of membrane or cytoplasmic proteins, including chaperones, on intermediate filaments ("scaffolding") appear as common molecular mechanisms and may explain the need for so many different keratin genes in vertebrates. PMID:27583190

  19. Deficits in Sustained Attention and Changes in Dopaminergic Protein Levels following Exposure to Proton Radiation Are Related to Basal Dopaminergic Function

    PubMed Central

    Davis, Catherine M.; DeCicco-Skinner, Kathleen L.; Hienz, Robert D.

    2015-01-01

    The current report assessed the effects of low-level proton irradiation in inbred adult male Fischer 344 and Lewis rats performing an analog of the human Psychomotor Vigilance Test (PVT), commonly utilized as an object risk assessment tool to quantify fatigue and sustained attention in laboratory, clinical, and operational settings. These strains were used to determine if genetic differences in dopaminergic function would impact radiation-induced deficits in sustained attention. Exposure to head-only proton irradiation (25 or 100 cGy) disrupted rPVT performance in a strain-specific manner, with 25 cGy-exposed Fischer 344 rats displaying the most severe deficits in sustained attention (i.e., decreased accuracy and increased premature responding); Lewis rats did not display behavioral deficits following radiation. Fischer 344 rats displayed greater tyrosine hydroxylase and dopamine transporter levels in the frontal cortex compared to the Lewis rats, even though radiation exposure increased both of these proteins in the Lewis rats only. Tyrosine hydroxylase was decreased in the parietal cortex of both rat strains following radiation exposure, regardless of proton dose. Strain-specific cytokine changes were also found in the frontal cortex, with the Lewis rats displaying increased levels of putative neurotrophic cytokines (e.g., CNTF). These data support the hypothesis that basal dopaminergic function impacts the severity of radiation-induced deficits in sustained attention. PMID:26658810

  20. Activated Acinus boosts basal autophagy

    PubMed Central

    Nandi, Nilay; Tyra, Lauren K; Krämer, Helmut

    2015-01-01

    Acinus (Acn) is a nuclear protein that participates in the regulation of autophagy. Loss of Acn function prevents autophagy in starving cells. Conversely, Acn activation induces basal autophagy. This enhances the quality control functions of autophagy such as the removal of misfolded proteins, thereby reducing neurodegeneration and prolonging lifespan. Acn activity is enhanced by Akt1-mediated phosphorylation, which counteracts the cleavage of Acn by a caspase-3 homolog. PMID:27308482

  1. Resting state functional connectivity of the basal nucleus of Meynert in humans: in comparison to the ventral striatum and the effects of age

    PubMed Central

    Li, Chiang-shan R.; Ide, Jaime S.; Zhang, Sheng; Hu, Sien; Chao, Herta H.; Zaborszky, Laszlo

    2014-01-01

    The basal nucleus of Meynert (BNM) provides the primary cholinergic inputs to the cerebral cortex. Loss of neurons in the BNM is linked to cognitive deficits in Alzheimer’s disease and other degenerative conditions. Numerous animal studies described cholinergic and non-cholinergic neuronal responses in the BNM; however, work in humans has been hampered by the difficulty of defining the BNM anatomically. Here, on the basis of a previous study that delineated the BNM of post-mortem human brains in a standard stereotaxic space, we sought to examine functional connectivity of the BNM, as compared to the nucleus accumbens (or ventral striatum, VS), in a large resting state functional magnetic resonance imaging data set. The BNM and VS shared but also showed a distinct pattern of cortical and subcortical connectivity. Compared to the VS, the BNM showed stronger positive connectivity with the putamen, pallidum, thalamus, amygdala and midbrain, as well as the anterior cingulate cortex, supplementary motor area and pre-supplementary motor area, a network of brain regions that respond to salient stimuli and orchestrate motor behavior. In contrast, compared to the BNM, the VS showed stronger positive connectivity with the ventral caudate and medial orbitofrontal cortex, areas implicated in reward processing and motivated behavior. Furthermore, the BNM and VS each showed extensive negative connectivity with visual and lateral prefrontal cortices. Together, the distinct cerebral functional connectivities support the role of the BNM in arousal, saliency responses and cognitive motor control and the VS in reward related behavior. Considering the importance of BNM in age-related cognitive decline, we explored the effects of age on BNM and VS connectivities. BNM connectivity to the visual and somatomotor cortices decreases while connectivity to subcortical structures including the midbrain, thalamus, and pallidum increases with age. These findings of age-related changes of

  2. Evidence for Conservation of the Calcitonin Superfamily and Activity-regulating Mechanisms in the Basal Chordate Branchiostoma floridae: INSIGHTS INTO THE MOLECULAR AND FUNCTIONAL EVOLUTION IN CHORDATES.

    PubMed

    Sekiguchi, Toshio; Kuwasako, Kenji; Ogasawara, Michio; Takahashi, Hiroki; Matsubara, Shin; Osugi, Tomohiro; Muramatsu, Ikunobu; Sasayama, Yuichi; Suzuki, Nobuo; Satake, Honoo

    2016-01-29

    The calcitonin (CT)/CT gene-related peptide (CGRP) family is conserved in vertebrates. The activities of this peptide family are regulated by a combination of two receptors, namely the calcitonin receptor (CTR) and the CTR-like receptor (CLR), and three receptor activity-modifying proteins (RAMPs). Furthermore, RAMPs act as escort proteins by translocating CLR to the cell membrane. Recently, CT/CGRP family peptides have been identified or inferred in several invertebrates. However, the molecular characteristics and relevant functions of the CTR/CLR and RAMPs in invertebrates remain unclear. In this study, we identified three CT/CGRP family peptides (Bf-CTFPs), one CTR/CLR-like receptor (Bf-CTFP-R), and three RAMP-like proteins (Bf-RAMP-LPs) in the basal chordate amphioxus (Branchiostoma floridae). The Bf-CTFPs were shown to possess an N-terminal circular region typical of the CT/CGRP family and a C-terminal Pro-NH2. The Bf-CTFP genes were expressed in the central nervous system and in endocrine cells of the midgut, indicating that Bf-CTFPs serve as brain and/or gut peptides. Cell surface expression of the Bf-CTFP-R was enhanced by co-expression with each Bf-RAMP-LP. Furthermore, Bf-CTFPs activated Bf-CTFP-R·Bf-RAMP-LP complexes, resulting in cAMP accumulation. These results confirmed that Bf-RAMP-LPs, like vertebrate RAMPs, are prerequisites for the function and translocation of the Bf-CTFP-R. The relative potencies of the three peptides at each receptor were similar. Bf-CTFP2 was a potent ligand at all receptors in cAMP assays. Bf-RAMP-LP effects on ligand potency order were distinct to vertebrate CGRP/adrenomedullin/amylin receptors. To the best of our knowledge, this is the first molecular and functional characterization of an authentic invertebrate CT/CGRP family receptor and RAMPs. PMID:26644465

  3. Arthroscopic resection of dorsal wrist ganglia and treatment of recurrences.

    PubMed

    Luchetti, R; Badia, A; Alfarano, M; Orbay, J; Indriago, I; Mustapha, B

    2000-02-01

    From 1995 to 1998, 30 patients with dorsal wrist ganglia and four with recurrent dorsal ganglia underwent arthroscopic resection. At a mean follow-up of 16 months, no complications were seen, but minimal pain persisted in three patients. Two recurrences were seen after arthroscopic resection of primary ganglia. PMID:10763721

  4. An analogue-sensitive approach identifies basal body rotation and flagellum attachment zone elongation as key functions of PLK in Trypanosoma brucei

    PubMed Central

    Lozano-Núñez, Ana; Ikeda, Kyojiro N.; Sauer, Thomas; de Graffenried, Christopher L.

    2013-01-01

    Polo-like kinases are important regulators of cell division, playing diverse roles in mitosis and cytoskeletal inheritance. In the parasite Trypanosoma brucei, the single PLK homologue TbPLK is necessary for the assembly of a series of essential organelles that position and adhere the flagellum to the cell surface. Previous work relied on RNA interference or inhibitors of undefined specificity to inhibit TbPLK, both of which have significant experimental limitations. Here we use an analogue-sensitive approach to selectively and acutely inhibit TbPLK. T. brucei cells expressing only analogue-sensitive TbPLK (TbPLKas) grow normally, but upon treatment with inhibitor develop defects in flagellar attachment and cytokinesis. TbPLK cannot migrate effectively when inhibited and remains trapped in the posterior of the cell throughout the cell cycle. Using synchronized cells, we show that active TbPLK is a direct requirement for the assembly and extension of the flagellum attachment zone, which adheres the flagellum to the cell surface, and for the rotation of the duplicated basal bodies, which positions the new flagellum so that it can extend without impinging on the old flagellum. This approach should be applicable to the many kinases found in the T. brucei genome that lack an ascribed function. PMID:23447704

  5. A novel gain-of-function STAT1 mutation resulting in basal phosphorylation of STAT1 and increased distal IFN-γ-mediated responses in chronic mucocutaneous candidiasis.

    PubMed

    Martinez-Martinez, Laura; Martinez-Saavedra, Maria Teresa; Fuentes-Prior, Pablo; Barnadas, Maria; Rubiales, Maria Victoria; Noda, Judith; Badell, Isabel; Rodríguez-Gallego, Carlos; de la Calle-Martin, Oscar

    2015-12-01

    Gain-of-function STAT1 mutations have recently been associated with autosomal dominant chronic mucocutaneous candidiasis (CMC). The purpose of this study was to characterize the three members of a non-consanguineous family, the father and his two sons, who presented with recurrent oral thrush and ocular candidiasis since early childhood. The three patients had reduced levels of IL-17-producing T cells. This reduction affected specifically IL-17(+)IFN-γ(-) T cells, because the levels of IL-17(+)IFN-γ(+) T cells were similar to controls. We found that PBMC (peripheral blood mononuclear cells) from the patients did not respond to Candida albicans ex vivo. Moreover, after polyclonal activation, patients' PBMC produced lower levels of IL-17 and IL-6 and higher levels of IL-4 than healthy controls. Genetic analyses showed that the three patients were heterozygous for a new mutation in STAT1 (c.894A>C, p.K298N) that affects a highly conserved residue of the coiled-coil domain of STAT1. STAT1 phosphorylation levels were significantly higher in patients' cells than in healthy controls, both in basal conditions and after IFN-γ stimulation, suggesting a permanent activation of STAT1. Cells from the patients also presented increased IFN-γ-mediated responses measured as MIG and IP-10 production. In conclusion, we report a novel gain-of-function mutation in the coiled-coil domain of STAT1, which increases STAT1 phosphorylation and impairs IL-17-mediated immunity. The mutation is responsible for CMC in this family with autosomal dominant inheritance of the disease. PMID:26514428

  6. 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

  7. NEURAL FACTORS IN THE DEVELOPMENT OF RENAL FUNCTION: NEONATAL CENTRAL CATECHOLAMINERGIC LESIONS ALTER THE RESPONSE TO EXOGENOUS VASOPRESSIN WITHOUT AFFECTING BASAL FUNCTION

    EPA Science Inventory

    Peripheral sympathetic neurons are thought to provide trophic regulatory signals for development of their target tissues. n the current study, we investigated the role of sympathetic tone in the functional development of the kidney in the rat, using intracisternal administration ...

  8. Basal cell cancer (image)

    MedlinePlus

    ... is needed to prove the diagnosis of basal cell carcinoma. Treatment varies depending on the size, depth, and location of the cancer. Early treatment by a dermatologist may result in a cure rate of more than 95%, but regular examination ...

  9. Basal cell skin cancer

    MedlinePlus

    ... occur in younger people who have had extensive sun exposure. You are more likely to get basal cell ... severe sunburns early in life Long-term daily sun exposure (such as the sun exposure received by people ...

  10. Basal ganglia—thalamus and the “crowning enigma”

    PubMed Central

    Garcia-Munoz, Marianela; Arbuthnott, Gordon W.

    2015-01-01

    When Hubel (1982) referred to layer 1 of primary visual cortex as “… a ‘crowning mystery’ to keep area-17 physiologists busy for years to come …” he could have been talking about any cortical area. In the 80’s and 90’s there were no methods to examine this neuropile on the surface of the cortex: a tangled web of axons and dendrites from a variety of different places with unknown specificities and doubtful connections to the cortical output neurons some hundreds of microns below. Recently, three changes have made the crowning enigma less of an impossible mission: the clear presence of neurons in layer 1 (L1), the active conduction of voltage along apical dendrites and optogenetic methods that might allow us to look at one source of input at a time. For all of those reasons alone, it seems it is time to take seriously the function of L1. The functional properties of this layer will need to wait for more experiments but already L1 cells are GAD67 positive, i.e., inhibitory! They could reverse the sign of the thalamic glutamate (GLU) input for the entire cortex. It is at least possible that in the near future normal activity of individual sources of L1 could be detected using genetic tools. We are at the outset of important times in the exploration of thalamic functions and perhaps the solution to the crowning enigma is within sight. Our review looks forward to that solution from the solid basis of the anatomy of the basal ganglia output to motor thalamus. We will focus on L1, its afferents, intrinsic neurons and its influence on responses of pyramidal neurons in layers 2/3 and 5. Since L1 is present in the whole cortex we will provide a general overview considering evidence mainly from the somatosensory (S1) cortex before focusing on motor cortex. PMID:26582979

  11. The Effects of Methylphenidate on Resting-State Functional Connectivity of the Basal Nucleus of Meynert, Locus Coeruleus, and Ventral Tegmental Area in Healthy Adults

    PubMed Central

    Kline, Ryan L.; Zhang, Sheng; Farr, Olivia M.; Hu, Sien; Zaborszky, Laszlo; Samanez-Larkin, Gregory R.; Li, Chiang-Shan R.

    2016-01-01

    Background: Methylphenidate (MPH) influences catecholaminergic signaling. Extant work examined the effects of MPH on the neural circuits of attention and cognitive control, but few studies have investigated the effect of MPH on the brain's resting-state functional connectivity (rsFC). Methods: In this observational study, we compared rsFC of a group of 24 healthy adults who were administered an oral 45 mg dose of MPH with a group of 24 age and gender matched controls who did not receive MPH. We focused on three seed regions: basal nucleus of Meynert (BNM), locus coeruleus (LC), and ventral tegmental area/substantia nigra, pars compacta (VTA/SNc), each providing cholinergic, noradrenergic and dopaminergic inputs to the cerebral cortex. Images were pre-processed and analyzed as in our recent work (Li et al., 2014; Zhang et al., 2015). We used one-sample t-test to characterize group-specific rsFC of each seed region and two-sample t-test to compare rsFC between groups. Results: MPH reversed negative connectivity between BNM and precentral gyri. MPH reduced positive connectivity between LC and cerebellum, and induced positive connectivity between LC and right hippocampus. MPH decreased positive VTA/SNc connectivity to the cerebellum and putamen, and reduced negative connectivity to left middle occipital gyrus. Conclusion: MPH had distinct effects on the rsFC of BNM, LC, and VTA/SNc in healthy adults. These new findings may further our understanding of the role of catecholaminergic signaling in Attention Deficit Hyperactivity Disorder (ADHD) and Parkinson's disease and provide insights into the therapeutic mechanisms of MPH in the treatment of clinical conditions that implicate catecholaminergic dysfunction. PMID:27148006

  12. Combined damage to entorhinal cortex and cholinergic basal forebrain neurons, two early neurodegenerative features accompanying Alzheimer's disease: effects on locomotor activity and memory functions in rats.

    PubMed

    Traissard, Natalia; Herbeaux, Karine; Cosquer, Brigitte; Jeltsch, Hélène; Ferry, Barbara; Galani, Rodrigue; Pernon, Anne; Majchrzak, Monique; Cassel, Jean-Christophe

    2007-04-01

    In Alzheimer's disease (AD), cognitive decline is linked to cholinergic dysfunctions in the basal forebrain (BF), although the earliest neuronal damage is described in the entorhinal cortex (EC). In rats, selective cholinergic BF lesions or fiber-sparing EC lesions may induce memory deficits, but most often of weak magnitude. This study investigated, in adult rats, the effects on activity and memory of both lesions, alone or in combination, using 192 IgG-saporin (OX7-saporin as a control) and L-N-methyl-D-aspartate to destroy BF and EC neurons, respectively. Rats were tested for locomotor activity in their home cage and for working- and/or reference-memory in various tasks (water maze, Hebb-Williams maze, radial maze). Only rats with combined lesions showed diurnal and nocturnal hyperactivity. EC lesions impaired working memory and induced anterograde memory deficits in almost all tasks. Lesions of BF cholinergic neurons induced more limited deficits: reference memory was impaired in the probe trial of the water-maze task and in the radial maze. When both lesions were combined, performance never improved in the water maze and the number of errors in the Hebb-Williams and the radial mazes was always larger than in any other group. These results (i) indicate synergistic implications of BF and EC in memory function, (ii) suggest that combined BF cholinergic and fiber-sparing EC lesions may model aspects of anterograde memory deficits and restlessness as seen in AD, (iii) challenge the cholinergic hypothesis of cognitive dysfunctions in AD, and (iv) contribute to open theoretical views on AD-related memory dysfunctions going beyond the latter hypothesis. PMID:16760925

  13. Renal Integrin-Linked Kinase Depletion Induces Kidney cGMP-Axis Upregulation: Consequences on Basal and Acutely Damaged Renal Function

    PubMed Central

    Cano-Peñalver, José Luis; Griera, Mercedes; García-Jerez, Andrea; Hatem-Vaquero, Marco; Ruiz-Torres, María Piedad; Rodríguez-Puyol, Diego; de Frutos, Sergio; Rodríguez-Puyol, Manuel

    2015-01-01

    Soluble guanylyl cyclase (sGC) is activated by nitric oxide (NO) and produces cGMP, which activates cGMP-dependent protein kinases (PKG) and is hydrolyzed by specific phosphodiesterases (PDE). The vasodilatory and cytoprotective capacity of cGMP-axis activation results in a therapeutic strategy for several pathologies. Integrin-linked kinase (ILK), a major scaffold protein between the extracellular matrix and intracellular signaling pathways, may modulate the expression and functionality of the cGMP-axis–related proteins. We introduce ILK as a novel modulator in renal homeostasis as well as a potential target for cisplatin (CIS)-induced acute kidney injury (AKI) improvement. We used an adult mice model of depletion of ILK (cKD-ILK), which showed basal increase of sGC and PKG expressions and activities in renal cortex when compared with wildtype (WT) littermates. Twenty-four h activation of sGC activation with NO enhanced the filtration rate in cKD-ILK. During AKI, cKD-ILK maintained the cGMP-axis upregulation with consequent filtration rates enhancement and ameliorated CIS-dependent tubular epithelial-to-mesenchymal transition and inflammation and markers. To emphasize the role of cGMP-axis upregulation due to ILK depletion, we modulated the cGMP axis under AKI in vivo and in renal cultured cells. A suboptimal dose of the PDE inhibitor ZAP enhanced the beneficial effects of the ILK depletion in AKI mice. On the other hand, CIS increased contractility-related events in cultured glomerular mesangial cells and necrosis rates in cultured tubular cells; ILK depletion protected the cells while sGC blockade with ODQ fully recovered the damage. PMID:26562149

  14. LACK OF FUNCTIONAL GABAB RECEPTORS ALTERS Kiss1, Gnrh1 AND Gad1 mRNA EXPRESSION IN THE MEDIAL BASAL HYPOTHALAMUS AT POSTNATAL DAY 4

    PubMed Central

    Di Giorgio, Noelia P.; Catalano, Paolo N.; López, Paula V.; González, Betina; Semaan, Sheila J.; López, Gabriela C.; Kauffman, Alexander S.; Rulli, Susana B.; Somoza, Gustavo M.; Bettler, Bernhard; Libertun, Carlos; Lux-Lantos, Victoria A.

    2013-01-01

    Background/Aims Adult mice lacking functional GABAB receptors (GABAB1KO) show altered Gnrh1 and Gad1 expressions in the preoptic area-anterior hypothalamus (POA-AH) and females display disruption of cyclicity and fertility. Here we addressed whether sexual differentiation of the brain and the proper wiring of the GnRH and kisspeptin systems were already disturbed in postnatal day 4 (PND4) GABAB1KO mice. Methods PND4 wild type (WT) and GABAB1KO mice of both sexes were sacrificed; tissues were collected to determine mRNA expression (qPCR), amino acids (HPLC), and hormones (RIA and/or IHC). Results GnRH neuron number (IHC) did not differ among groups in olfactory bulbs or OVLT-POA. Gnrh1 mRNA (qPCR) in POA-AH was similar among groups. Gnrh1 mRNA in medial basal hypothalamus (MBH) was similar in WTs but was increased in GABAB1KO females compared to GABAB1KO males. Hypothalamic GnRH (RIA) was sexually different in WTs (males > females) but this sex difference was lost in GABAB1KOs; the same pattern was observed when analyzing only the MBH, but not in the POA-AH. Arcuate nucleus Kiss1 mRNA (micropunch-qPCR) was higher in WT females than in WT males and GABAB1KO females. Gad1 mRNA in MBH was increased in GABAB1KO females compared to GABAB1KO males. Serum LH and gonadal estradiol content were also increased in GABAB1KOs. Conclusion We demonstrate that GABABRs participate in the sexual differentiation of the ARC/MBH, because sex differences in several reproductive genes, such as Gad1, Kiss1 and Gnrh1, are critically disturbed in GABAB1KO mice at PND4, probably altering the organization and development of neural circuits governing the reproductive axis. PMID:24080944

  15. [Arthroscopic resection of dorsal wrist ganglia].

    PubMed

    Borisch, N

    2014-10-01

    In arthroscopic wrist surgery, the resection of dorsal wrist ganglia has become a well accepted practice. As advantages for the minimally invasive procedure the low complication rate and low postoperative morbidity, less postoperative pain and faster recovery over open techniques are discussed. The possibility to assess accompanying joint pathology is considered as another advantage. The importance of identifying a so-called ganglion cyst stalk seems to have been overstated. Regarding the technique, the main discussion points are the size and localisation of the capsular window and the necessity of additional midcarpal arthroscopy. The possibility and results of treatment of recurrent ganglion cysts are still controversial. Our own experience and that of some authors are positive. Hardly mentioned in the literature is the treatment of occult dorsal wrist ganglia and its results, which is considered as very successful by the authors. PMID:25290273

  16. [Arthroscopic treatment of dorsal wrist ganglia].

    PubMed

    Dumontier, C; Chaumeil, G; Chassat, R; Nourissat, G

    2006-11-01

    Incidentally discovered in 1987, arthroscopic treatment of dorsal wrist ganglia is based on our knowledge of their physiopathology which in turn benefits from the arthroscopic wrist evaluation. Dorsal wrist ganglia arise in the radiocarpal space from the dorsal part of the scapholunate ligament and migrate along the dorsal wrist capsule. According to their position above or under the dorsal intercarpal ligament, their cutaneous projection may vary. The basis of the arthroscopic treatment of wrist ganglia is, as with open surgery, the capsular resection in front of their origin. Arthroscopic resection is made either from dorsal radio-carpal or midcarpal approaches with little morbidity. Scars are unnoticeable, wrist mobility and strength close to normal by three months, which is the delay for dorsal wrist pain, always very limited, to disappear. The recurrence rate is however still debatable. Close to zero in some series, we had almost 20% recurrence rate in our series, with half of patients who reccur after two years follow-up. This variability in the recurrence rate also exists with open techniques. The only prospective and randomized study available to date found no differences between the two techniques, according to the recurrence rate. PMID:17361892

  17. Thermodynamic significance of human basal metabolism

    NASA Astrophysics Data System (ADS)

    Wang, Cuncheng

    1993-06-01

    The human basal state, a non-equilibrium steady state, is analysed in this paper in the light of the First and Second Laws of Thermodynamics whereby the thermodynamic significance of the basal metabolic rate and its distinction to the dissipation function and exergy loss are identified. The analysis demonstrates the correct expression of the effects of the blood flow on the heat balance in a human-body bio-heat model and the relationship between the basal metabolic rate and the blood perfusion.

  18. Unveiling the origin of the basal-plane antiferromagnetism in the spin–orbit Mott insulator Ba2IrO4: a density functional and model Hamiltonian study

    NASA Astrophysics Data System (ADS)

    Hou, Y. S.; Xiang, H. J.; Gong, X. G.

    2016-04-01

    Based on the density functional theory and model Hamiltonian, we studied the basal-plane antiferromagnetism in the spin–orbit Mott insulator Ba2IrO4. By comparing the magnetic properties of the bulk Ba2IrO4 with those of the single-layer Ba2IrO4, we demonstrate unambiguously that the basal-plane antiferromagnetism is caused by the intralyer magnetic interactions rather than by the previously proposed interlayer ones. Aiming at revealing the origin of the basal-plane antiferromagnetism, we add the single ion anisotropy and pseudo-quadrupole interactions into the general bilinear pseudo-spin Hamiltonian. The obtained magnetic interaction parameters indicate that the single ion anisotropy and pseudo-quadrupole interactions are unexpectedly strong. Systematical Monte Carlo simulations demonstrate that the basal-plane antiferromagnetism is caused by isotropic Heisenberg, bond-dependent Kitaev and pseudo-quadrupole interactions. On the basis of this study the single ion anisotropy and pseudo-quadrupole interactions could play a role in explaining magnetic interactions in other iridates.

  19. Measuring localization and diffusion coefficients of basolateral proteins in lateral versus basal membranes using functionalized substrates and kICS analysis.

    PubMed

    Marlar, Saw; Arnspang, Eva C; Pedersen, Gitte A; Koffman, Jennifer S; Nejsum, Lene N

    2014-10-01

    Micropatterning enabled semiquantitation of basolateral proteins in lateral and basal membranes of the same cell. Lateral diffusion coefficients of basolateral aquaporin-3 (AQP3-EGFP) and EGFP-AQP4 were extracted from "lateral" and "basal" membranes using identical live-cell imaging and k-space Image Correlation Spectroscopy (kICS). To simultaneously image proteins in "lateral" and "basal" membranes, micropatterning with the extracellular domain of E-cadherin and collagen, to mimic cell-cell and cell-extracellular matrix (ECM) adhesion, respectively, was used. In kidney collecting duct principal cells AQP3 localizes lateral and basal whereas AQP4 localizes mainly basal. On alternating stripes of E-cadherin and collagen, AQP3-EGFP was predominantly localized to "lateral" compared to "basal" membranes, whereas Orange-AQP4 was evenly distributed. Average diffusion coefficients were extracted via kICS analysis of rapid time-lapse sequences of AQP3-EGFP and EGFP-AQP4 on uniform substrates of either E-cadherin or collagen. AQP3-EGFP was measured to 0.022±0.010μm(2)/s on E-cadherin and 0.019±0.004μm(2)/s on collagen, whereas EGFP-AQP4 was measured to 0.044±0.009μm(2)/s on E-cadherin and 0.037±0.009μm(2)/s on collagen, thus, diffusion did not differ between substrates. Cholesterol depletion by methyl-beta-cyclodextrin (MBCD) reduced the AQP3-EGFP diffusion coefficient by 43% from 0.024±0.007μm(2)/s (water) to 0.014±0.003μm(2)/s (MBCD) (p<0.05) on collagen surfaces, and by 41% from 0.023±0.011μm(2)/s (water) to 0.014±0.005μm(2)/s (MBCD) (p<0.05) on E-cadherin surfaces. Thus, protein patterning enables the semiquantitation of protein distribution between the "lateral" and "basal" membranes as well as measurements of lateral diffusion coefficients. PMID:24950246

  20. Severity of Dysfluency Correlates with Basal Ganglia Activity in Persistent Developmental Stuttering

    ERIC Educational Resources Information Center

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

    2008-01-01

    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,…

  1. Abnormal Responses to Monetary Outcomes in Cortex, but not in the Basal Ganglia, in Schizophrenia

    PubMed Central

    Waltz, James A; Schweitzer, Julie B; Ross, Thomas J; Kurup, Pradeep K; Salmeron, Betty J; Rose, Emma J; Gold, James M; Stein, Elliot A

    2010-01-01

    Psychosis has been associated with aberrant brain activity concurrent with both the anticipation and integration of monetary outcomes. The extent to which abnormal reward-related neural signals can be observed in chronic, medicated patients with schizophrenia (SZ), however, is not clear. In an fMRI study involving 17 chronic outpatients with SZ and 17 matched controls, we used a monetary incentive delay (MID) task, in which different-colored shapes predicted gains, losses, or neutral outcomes. Subjects needed to respond to a target within a time window in order to receive the indicated gain or avoid the indicated loss. Group differences in blood-oxygen-level-dependent responses to cues and outcomes were assessed through voxel-wise whole-brain analyses and regions-of-interest analyses in the neostriatum and prefrontal cortex (PFC). Significant group by outcome valence interactions were observed in the medial and lateral PFC, lateral temporal cortex, and amygdalae, such that controls, but not patients, showed greater activation for gains, relative to losses. In the striatum, neural activity was modulated by outcome magnitude in both groups. Additionally, we found that ratings of negative symptoms in patients correlated with sensitivity to obtained losses in medial PFC, obtained gains in lateral PFC, and anticipated gains in left ventral striatum. Sensitivity to obtained gains in lateral PFC also correlated with positive symptom scores in patients. Our findings of systematic relationships between clinical symptoms and neural responses to stimuli associated with rewards and punishments offer promise that reward-related neural responses may provide sensitive probes of the effectiveness of treatments for negative symptoms. PMID:20720534

  2. Optical coherence tomography imaging of the basal ganglia: feasibility and brief review.

    PubMed

    Lopez, W O Contreras; Ângelos, J S; Martinez, R C R; Takimura, C K; Teixeira, M J; Lemos Neto, P A; Fonoff, E T

    2015-12-01

    Optical coherence tomography (OCT) is a promising medical imaging technique that uses light to capture real-time cross-sectional images from biological tissues in micrometer resolution. Commercially available optical coherence tomography systems are employed in diverse applications, including art conservation and diagnostic medicine, notably in cardiology and ophthalmology. Application of this technology in the brain may enable distinction between white matter and gray matter, and obtainment of detailed images from within the encephalon. We present, herein, the in vivo implementation of OCT imaging in the rat brain striatum. For this, two male 60-day-old rats (Rattus norvegicus, Albinus variation, Wistar) were stereotactically implanted with guide cannulas into the striatum to guide a 2.7-French diameter high-definition OCT imaging catheter (Dragonfly™, St. Jude Medical, USA). Obtained images were compared with corresponding histologically stained sections to collect imaging samples. A brief analysis of OCT technology and its current applications is also reported, as well as intra-cerebral OCT feasibility on brain mapping during neurosurgical procedures. PMID:26421868

  3. A Computational Model of Inhibitory Control in Frontal Cortex and Basal Ganglia

    ERIC Educational Resources Information Center

    Wiecki, Thomas V.; Frank, Michael J.

    2013-01-01

    Planning and executing volitional actions in the face of conflicting habitual responses is a critical aspect of human behavior. At the core of the interplay between these 2 control systems lies an override mechanism that can suppress the habitual action selection process and allow executive control to take over. Here, we construct a neural circuit…

  4. Optical coherence tomography imaging of the basal ganglia: feasibility and brief review

    PubMed Central

    Lopez, W. O. Contreras; Ângelos, J. S.; Martinez, R. C. R.; Takimura, C. K.; Teixeira, M. J.; Lemos, P. A.; Fonoff, E. T.

    2015-01-01

    Optical coherence tomography (OCT) is a promising medical imaging technique that uses light to capture real-time cross-sectional images from biological tissues in micrometer resolution. Commercially available optical coherence tomography systems are employed in diverse applications, including art conservation and diagnostic medicine, notably in cardiology and ophthalmology. Application of this technology in the brain may enable distinction between white matter and gray matter, and obtainment of detailed images from within the encephalon. We present, herein, the in vivo implementation of OCT imaging in the rat brain striatum. For this, two male 60-day-old rats (Rattus norvegicus, Albinus variation, Wistar) were stereotactically implanted with guide cannulas into the striatum to guide a 2.7-French diameter high-definition OCT imaging catheter (Dragonfly™, St. Jude Medical, USA). Obtained images were compared with corresponding histologically stained sections to collect imaging samples. A brief analysis of OCT technology and its current applications is also reported, as well as intra-cerebral OCT feasibility on brain mapping during neurosurgical procedures. PMID:26421868

  5. Differential activation of dopaminergic systems in rat brain basal ganglia by morphine and methamphetamine.

    PubMed

    Mori, T; Iwase, Y; Saeki, T; Iwata, N; Murata, A; Masukawa, D; Suzuki, T

    2016-05-13

    Typical abused drug-induced behavioral changes are ordinarily mediated by the mesolimbic dopaminergic system and even the phenotypes of behavior are different from each other. However, the mechanisms that underlie the behavioral changes induced by these abused drugs have not yet been elucidated. The present study was designed to investigate the mechanisms that underlie how abused drugs induce distinct behavioral changes using neurochemical as well as behavioral techniques in rats. Methamphetamine (2mg/kg) more potently increased dopamine release from the striatum more than that from the nucleus accumbens. In contrast, the administration of morphine (10mg/kg) produced a significant increase in the release of dopamine from the nucleus accumbens, but not the striatum, which is accompanied by a decrease in the release of GABA in the ventral tegmental area. These findings indicate that morphine and methamphetamine differentially regulate dopaminergic systems to produce behavioral changes, even though both drugs have abuse potential through activation of the mesolimbic dopaminergic system. PMID:26820597

  6. Abnormal responses to monetary outcomes in cortex, but not in the basal ganglia, in schizophrenia.

    PubMed

    Waltz, James A; Schweitzer, Julie B; Ross, Thomas J; Kurup, Pradeep K; Salmeron, Betty J; Rose, Emma J; Gold, James M; Stein, Elliot A

    2010-11-01

    Psychosis has been associated with aberrant brain activity concurrent with both the anticipation and integration of monetary outcomes. The extent to which abnormal reward-related neural signals can be observed in chronic, medicated patients with schizophrenia (SZ), however, is not clear. In an fMRI study involving 17 chronic outpatients with SZ and 17 matched controls, we used a monetary incentive delay (MID) task, in which different-colored shapes predicted gains, losses, or neutral outcomes. Subjects needed to respond to a target within a time window in order to receive the indicated gain or avoid the indicated loss. Group differences in blood-oxygen-level-dependent responses to cues and outcomes were assessed through voxel-wise whole-brain analyses and regions-of-interest analyses in the neostriatum and prefrontal cortex (PFC). Significant group by outcome valence interactions were observed in the medial and lateral PFC, lateral temporal cortex, and amygdalae, such that controls, but not patients, showed greater activation for gains, relative to losses. In the striatum, neural activity was modulated by outcome magnitude in both groups. Additionally, we found that ratings of negative symptoms in patients correlated with sensitivity to obtained losses in medial PFC, obtained gains in lateral PFC, and anticipated gains in left ventral striatum. Sensitivity to obtained gains in lateral PFC also correlated with positive symptom scores in patients. Our findings of systematic relationships between clinical symptoms and neural responses to stimuli associated with rewards and punishments offer promise that reward-related neural responses may provide sensitive probes of the effectiveness of treatments for negative symptoms. PMID:20720534

  7. Function approximation in inhibitory networks.

    PubMed

    Tripp, Bryan; Eliasmith, Chris

    2016-05-01

    In performance-optimized artificial neural networks, such as convolutional networks, each neuron makes excitatory connections with some of its targets and inhibitory connections with others. In contrast, physiological neurons are typically either excitatory or inhibitory, not both. This is a puzzle, because it seems to constrain computation, and because there are several counter-examples that suggest that it may not be a physiological necessity. Parisien et al. (2008) showed that any mixture of excitatory and inhibitory functional connections could be realized by a purely excitatory projection in parallel with a two-synapse projection through an inhibitory population. They showed that this works well with ratios of excitatory and inhibitory neurons that are realistic for the neocortex, suggesting that perhaps the cortex efficiently works around this apparent computational constraint. Extending this work, we show here that mixed excitatory and inhibitory functional connections can also be realized in networks that are dominated by inhibition, such as those of the basal ganglia. Further, we show that the function-approximation capacity of such connections is comparable to that of idealized mixed-weight connections. We also study whether such connections are viable in recurrent networks, and find that such recurrent networks can flexibly exhibit a wide range of dynamics. These results offer a new perspective on computation in the basal ganglia, and also perhaps on inhibitory networks within the cortex. PMID:26963256

  8. Expression of Tas1 Taste Receptors in Mammalian Spermatozoa: Functional Role of Tas1r1 in Regulating Basal Ca2+ and cAMP Concentrations in Spermatozoa

    PubMed Central

    Meyer, Dorke; Voigt, Anja; Widmayer, Patricia; Borth, Heike; Huebner, Sandra; Breit, Andreas; Marschall, Susan; de Angelis, Martin Hrabé; Boehm, Ulrich; Meyerhof, Wolfgang; Gudermann, Thomas; Boekhoff, Ingrid

    2012-01-01

    Background During their transit through the female genital tract, sperm have to recognize and discriminate numerous chemical compounds. However, our current knowledge of the molecular identity of appropriate chemosensory receptor proteins in sperm is still rudimentary. Considering that members of the Tas1r family of taste receptors are able to discriminate between a broad diversity of hydrophilic chemosensory substances, the expression of taste receptors in mammalian spermatozoa was examined. Methodology/Principal Findings The present manuscript documents that Tas1r1 and Tas1r3, which form the functional receptor for monosodium glutamate (umami) in taste buds on the tongue, are expressed in murine and human spermatozoa, where their localization is restricted to distinct segments of the flagellum and the acrosomal cap of the sperm head. Employing a Tas1r1-deficient mCherry reporter mouse strain, we found that Tas1r1 gene deletion resulted in spermatogenic abnormalities. In addition, a significant increase in spontaneous acrosomal reaction was observed in Tas1r1 null mutant sperm whereas acrosomal secretion triggered by isolated zona pellucida or the Ca2+ ionophore A23187 was not different from wild-type spermatozoa. Remarkably, cytosolic Ca2+ levels in freshly isolated Tas1r1-deficient sperm were significantly higher compared to wild-type cells. Moreover, a significantly higher basal cAMP concentration was detected in freshly isolated Tas1r1-deficient epididymal spermatozoa, whereas upon inhibition of phosphodiesterase or sperm capacitation, the amount of cAMP was not different between both genotypes. Conclusions/Significance Since Ca2+ and cAMP control fundamental processes during the sequential process of fertilization, we propose that the identified taste receptors and coupled signaling cascades keep sperm in a chronically quiescent state until they arrive in the vicinity of the egg - either by constitutive receptor activity and/or by tonic receptor activation by

  9. Articular ganglia of the volar aspect of the wrist: arthroscopic resection compared with open excision. A prospective randomised study.

    PubMed

    Rocchi, Lorenzo; Canal, Alessandra; Fanfani, Francesco; Catalano, Francesco

    2008-01-01

    Our aim was to compare two methods of treatment of ganglia on the volar aspect of the wrist (the open excision done through a longitudinal volar skin incision and the arthroscopic resection through two or three dorsal ports), to see if arthroscopy could reduce the risks of operating in this area and the time to healing. Twenty radiocarpal and five midcarpal volar ganglia were operated on by open approach and an equivalent group was treated by arthroscopy. Fifteen radiocarpal and five midcarpal ganglia were treated with good results in the open group and 18 radiocarpal and one midcarpal ganglia in the arthroscopic group (no visible or palpable ganglion, a full range of active wrist movement, grip strength equal to preoperatively, no pain, and a cosmetically acceptable scar). In the open group there were four injuries to a branch of the radial artery, two cases of partial stiffness of the wrist associated with a painful scar, one case of neuropraxia, and one recurrence (all of which were among the 20 radiocarpal ganglia). In the arthroscopic group there was one case of neuropraxia, one injury to a branch of the radial artery, and three recurrences (three of the complications were among the five midcarpal ganglia). The mean functional recovery time was equal to 15 (6) days in the open group and 6 (2) days in the arthroscopic group. The mean time lost from work was equal to 23 (11) days in the open group and 10 (5) days in the arthroscopic group. Our results suggest that arthroscopic resection is a reasonable alternative to open excision in treating radiocarpal volar ganglia because it has less postoperative morbidity and a better cosmetic result. Midcarpal volar ganglia, however, should still be treated by open operation. PMID:18791910

  10. Life beyond the Basal.

    ERIC Educational Resources Information Center

    Grey, Jeanne; Carbone, Carole

    1987-01-01

    Reading is a tool for learning. The goal for the teaching of reading must be to produce lovers of reading. A holistic approach should replace exclusive dependence on basal readers. Effective methods are the following: (1) language experience approach; (2) word banks; (3) pattern books; (4) sustained silent reading; and (5) directed…

  11. 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

  12. Drosophila melanogaster as a model for basal body research.

    PubMed

    Jana, Swadhin Chandra; Bettencourt-Dias, Mónica; Durand, Bénédicte; Megraw, Timothy L

    2016-01-01

    The fruit fly, Drosophila melanogaster, is one of the most extensively studied organisms in biological research and has centrioles/basal bodies and cilia that can be modelled to investigate their functions in animals generally. Centrioles are nine-fold symmetrical microtubule-based cylindrical structures required to form centrosomes and also to nucleate the formation of cilia and flagella. When they function to template cilia, centrioles transition into basal bodies. The fruit fly has various types of basal bodies and cilia, which are needed for sensory neuron and sperm function. Genetics, cell biology and behaviour studies in the fruit fly have unveiled new basal body components and revealed different modes of assembly and functions of basal bodies that are conserved in many other organisms, including human, green algae and plasmodium. Here we describe the various basal bodies of Drosophila, what is known about their composition, structure and function. PMID:27382461

  13. RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors

    PubMed Central

    Flegel, Caroline; Schöbel, Nicole; Altmüller, Janine; Becker, Christian; Tannapfel, Andrea; Hatt, Hanns; Gisselmann, Günter

    2015-01-01

    The chemosensory capacity of the somatosensory system relies on the appropriate expression of chemoreceptors, which detect chemical stimuli and transduce sensory information into cellular signals. Knowledge of the complete repertoire of the chemoreceptors expressed in human sensory ganglia is lacking. This study employed the next-generation sequencing technique (RNA-Seq) to conduct the first expression analysis of human trigeminal ganglia (TG) and dorsal roo