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Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease
Open accessAbstract
Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action.
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“Conversely, in PD, the early and preferential loss of DA in the dorsal basal ganglia leads to diminished automatic and increased cognitive (frontal cortex) control of motor movements.”
From Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease (2013) · cites this paper as [2]
In the citing paper
“Consequently, individuals with PD must handle and sustain a larger cognitive load to execute either motor or cognitive tasks2, 3.”
From Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease (2013) · cites this paper as [2]
In the citing paper
“In healthy individuals, motor performance is dependent on the interaction between unconscious (automatic) and volitional (cognitive) control of movement 1, 2.”
From Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease (2013) · cites this paper as [2]
In the citing paper
“The basal ganglia and its cortical connections also play an essential role in procedural motor learning, including the acquisition and retention of automaticity (For review see 2, 127).”
From Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease (2013) · cites this paper as [2]
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Cites
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Items 201–300 of 999
Striatal Direct Pathway Targets Npas1 + Pallidal Neurons
Cui, Q., Du, X., Chang, I. Y. M., Pamukcu, A., Lilascharoen, V., Berceau, B. L., García, D., Hong, D., Chon, U., Narayanan, A., et al. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.2306-20.2021 · Cited by 58
Steiner, H., & Waes, V. V. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.10.001 · Cited by 58
“…that arise in the cortex and project in a topographical manner to the striatum and from there via the basal ganglia output nuclei and thalamus back to the cortex (Alexander et al., 1986, 1990; Albin et al., 1989; Groenewegen et al., 1990; Haber, 2003; Joel and Weiner, 1994; Redgrave et al., 2010).”
Ginis, P., Heremans, E., Ferrari, A., Bekkers, E. M. J., Canning, C. G., & Nieuwboer, A. (2017) · Journal of Neurology · doi:10.1007/s00415-017-8552-6 · Cited by 57
Sensorimotor Processing in the Basal Ganglia Leads to Transient Beta Oscillations during Behavior
Mirzaei, A., Kumar, A., Leventhal, D., Mallet, N. P., Aertsen, A., Berke, J. D., & Schmidt, R. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1289-17.2017 · Cited by 56
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“…prefrontal cortex as well as the lateral temporal cortex are connected to the striatum forming cortico-striatal loops involved in executive function, including working memory, planning and selection processes (Alexander et al., 1986; Monchi et al., 2007; Nakano et al., 2000; Redgrave et al., 2010).”
BackgroundMizes, K. G. C., Lindsey, J. W., Escola, G. S., & Ölveczky, B. P. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01431-3 · Cited by 52
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Simonyan, K., Herscovitch, P., & Horwitz, B. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2012.12.042 · Cited by 57
“…of dopamine as a major neurotransmitter in the brain in 1950s (Carlsson, 1959), itsmodulatory effects onneural activity and networks have been shown to influence a wide range of human behaviors (Montague et al., 2004; Redgrave et al., 2010; Salimpoor et al., 2011; van Schouwenburg et al., 2010).”
BackgroundMezzarobba, S., Grassi, M., Pellegrini, L., Catalan, M., Krüger, B., Furlanis, G., Manganotti, P., & Bernardis, P. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2017.00723 · Cited by 57
Habits are negatively regulated by histone deacetylase 3 in the dorsal striatum
Malvaez, M., Greenfield, V. Y., Matheos, D. P., Angelillis, N. A., Murphy, M. D., Kennedy, P. J., Wood, M. A., & Wassum, K. M. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.01.025 · Cited by 56
Integrating the Roles of Midbrain Dopamine Circuits in Behavior and Neuropsychiatric Disease
Chen, A. P. F., Chen, L., Kim, T. A., & Xiong, Q. (2021) · Biomedicines · doi:10.3390/biomedicines9060647 · Cited by 59
Yun, S. J., Hyun, S. E., Oh, B., & Seo, H. G. (2023) · Journal of NeuroEngineering and Rehabilitation · doi:10.1186/s12984-023-01215-7 · Cited by 58
“The goal-directed mode, slow and serial, requires immense cognitive effort compared to stimulus response-habitual responding, making the behavior of patients with PD more susceptible to interference from other goal-oriented tasks [5].”
BackgroundManza, P., Zhang, S., Hu, S., Chao, H. H., Leung, H., & Li, C. R. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.12.016 · Cited by 57
“…these circuits are implicated in maintenance and updating of working memory (Hazy et al., 2006), control of goal-directed and habitual behavior (Redgrave et al., 2010), reward-based learning (Berridge and Robinson, 1998; Schultz, 2002; Wise, 2004), control of posture and movement (Delong et…”
BackgroundChersi, F., Mirolli, M., Pezzulo, G., & Baldassarre, G. (2012) · Neural Networks · doi:10.1016/j.neunet.2012.11.009 · Cited by 57
“This behavior is in line with experimental results showing that during goal-directed actions the prefrontal cortex overrides automatic stimulus-driven responses (Ashby, Turner, & Horvitz, 2010; de Wit, Barker, Dickinson, & Cools, 2011; Redgrave et al., 2010).”
ResultNelson, A. B., Hang, G. B., Grueter, B. A., Pascoli, V., Lüscher, C., Malenka, R. C., & Kreitzer, A. C. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0224-12.2012 · Cited by 56
“Conditioned responses were defined as trials during which the mouse left the chamber after the light came on, but before the shock being delivered ( 4 s).”
BackgroundDelgado‐Alvarado, M., Marano, M., Santurtún, A., Urtiaga‐Gallano, A., Tordesillas‐Gutiérrez, D., & Infante, J. (2019) · Movement Disorders · doi:10.1002/mds.27913 · Cited by 55
“Auditory cues applied continuously may drive, similar to visual cues, a goal-directed mode of motor control as a way to overcome the loss of habitual regulation.(81) It has been suggested that PD patients have largely predictive auditory cue utilization, which facilitates basal ganglia/premotor cortex interactions.”
BackgroundWatson, G. D. R., Smith, J. B., & Alloway, K. D. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1606-15.2015 · Cited by 54
“Comparison of collicular and pallidal connections Some recent studies had reported that the superior colliculus projects strongly to STN (Coizet et al., 2009; Redgrave et al., 2010a).”
BackgroundResultInfluentialWhat predicts cognitive decline in de novo Parkinson's disease?
Arnaldi, D., Campus, C., Ferrara, M., Famà, F., Picco, A., Carli, F. D., Accardo, J., Brugnolo, A., Sambuceti, G., Morbelli, S. D., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.11.028 · Cited by 54
Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia
Lee, H. M., Kwon, K., Kim, M.-J., Jang, J.-W., Suh, S., Koh, S., & Kim, J. H. (2014) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2014.03.009 · Cited by 54
“The ventral striatum, also called limbic striatum, is mostly comprised of the nucleus accumbens and ventromedial putamen, and has been proposed to play an important role in emotional, cognitive, andmotivational functions [23].”
BackgroundMapping microstructural gradients of the human striatum in normal aging and Parkinson’s disease
Drori, E., Berman, S., & Mezer, A. (2022) · Science Advances · doi:10.1126/sciadv.abm1971 · Cited by 52
Abundance Compensates Kinetics: Similar Effect of Dopamine Signals on D1 and D2 Receptor Populations
Hunger, L., Kumar, A., & Schmidt, R. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.1951-19.2019 · Cited by 54
“…neurons by changing their excitability (Day et al., 2008) and strength of synaptic inputs (Reynolds et al., 2001) in the context of motor control (Syed et al., 2016), action-selection (Redgrave et al., 2010), reinforcement learning (Schultz, 2007), and addiction (Everitt and Robbins, 2005).”
BackgroundCortical Correlates of Gait Compensation Strategies in Parkinson Disease
Tosserams, A., Weerdesteyn, V., Bal, T., Bloem, B. R., Solis‐Escalante, T., & Nonnekes, J. H. (2022) · Annals of Neurology · doi:10.1002/ana.26306 · Cited by 53
“These alternative pathways likely involve corticostriatal loops that rely on different modes of gait control (ie, goal-directed or emotional) compared to the primary automatic mode of gait control via the posterior putamen, which is most affected by dopaminergic denervation in Parkinson disease.(5,51)”
BackgroundResultBolo, N. R., Musen, G., Simonson, D. C., Nickerson, L. D. H., Flores, V. L., Siracusa, T., Hager, B. M., Lyoo, I. K., Renshaw, P. F., & Jacobson, A. M. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0319-15.2015 · Cited by 53
“The basal ganglia are involved in motor learning, motivation, and control of habitual behavior (Redgrave et al., 2010).”
BackgroundPal, G. D., O’Keefe, J. A., Robertson-Dick, E. E., Bernard, B. A., Anderson, S., & Hall, D. A. (2016) · Journal of NeuroEngineering and Rehabilitation · doi:10.1186/s12984-016-0205-y · Cited by 52
“However as the disease progresses and attentional circuitry becomes increasingly abnormal [57], PD patients are likely less able to compensate [56] and have reduced pace as a result [51].”
BackgroundMethodInfluentialRoet, M., Boonstra, J. T., Şahin, E., Mulders, A. E. P., Leentjens, A. F. G., & Jahanshahi, A. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9092729 · Cited by 56
“In contrast to the motor system that is studied thoroughly [90,91], emotional circuitry is far less understood.”
BackgroundCosentino, C., Putzolu, M., Mezzarobba, S., Cecchella, M., Innocenti, T., Bonassi, G., Botta, A., Lagravinese, G., Avanzino, L., & Pelosin, E. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105189 · Cited by 50
Synthetic consciousness: the distributed adaptive control perspective
Verschure, P. F. M. J. (2016) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2015.0448 · Cited by 54
Progress in LRRK2-Associated Parkinson’s Disease Animal Models
Seegobin, S. P., Heaton, G. R., Liang, D., Choi, I., Ramírez, M. B., Tang, B., & Yue, Z. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00674 · Cited by 52
Klug, J. R., Mathur, B. N., Kash, T. L., Wang, H.-D., Matthews, R. T., Robison, A. J., Anderson, M. E., Deutch, A. Y., Lovinger, D. M., Colbran, R. J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045323 · Cited by 49
Kim, H., Kim, E., Yun, S. J., Kang, M., Shin, H. I., Oh, B., & Seo, H. G. (2022) · Annals of Physical and Rehabilitation Medicine · doi:10.1016/j.rehab.2021.101620 · Cited by 51
Encoding by Synchronization in the Primate Striatum
Adler, A., Finkes, I., Katabi, S., Prut, Y., & Bergman, H. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4791-12.2013 · Cited by 56
Stress improves task processing efficiency in dual-tasks
Beste, C., Yildiz, A., Meissner, T. W., & Wolf, O. T. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.06.013 · Cited by 50
Gait in Parkinson’s disease: A visuo-cognitive challenge
Stuart, S., Lord, S., Hill, E., & Rochester, L. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.01.002 · Cited by 55
“Abnormal visual processing within BG loops is also suggested to cause people with PD to become reliant on attentional compensation (Redgrave et al., 2010).”
Parkinson's disease: Is it a consequence of human brain evolution?
Diederich, N. J., Surmeier, D. J., Uchihara, T., Grillner, S. E., & Goetz, C. G. (2019) · Movement Disorders · doi:10.1002/mds.27628 · Cited by 48
“” When the BG is impaired, control becomes slower and less efficient; moreover, the ability to generate rapid, stimulusdriven, habitual motor sequences is largely lost.(11) The largest of the BG nuclei is the striatum; it integrates information from other telencephalic structures—”
BackgroundCascella, N. G., Butala, A., Mills, K. A., Kim, M. J., Salimpour, Y., Wojtasievicz, T., Hwang, B. Y., Cullen, B., Figee, M., Moran, L. V., et al. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.03.007 · Cited by 48
Reaching and Grasping Movements in Parkinson’s Disease: A Review
Fasano, A., Mazzoni, A., & Falotico, E. (2022) · Journal of Parkinson s Disease · doi:10.3233/jpd-213082 · Cited by 48
“tion of external sensory cues may help bypassing the 625 damaged habitual control loops in the BG (caudal 626 putamen) and allow a direct involvement of the pre627 served goal-directed control ones (STN, GPe) [72], 628 thus enhancing the motor performances.”
BackgroundInfluentialSequential movement skill in Parkinson's disease: A state-of-the-art
Ruitenberg, M. F. L., Duthoo, W., Santens, P., Notebaert, W., & Abrahamse, E. L. (2015) · Cortex · doi:10.1016/j.cortex.2015.01.005 · Cited by 48
“As their ability to learn and perform sequential movements in an automatic fashion is impaired due to DA depletion in the sensorimotor striatum, PD patients may engage in a more goal-directed mode of sequential action control, which relies on the relatively spared associative striatum (Redgrave et al., 2010).”
BackgroundHerz, D. M., Florin, E., Christensen, M. S., Reck, C., Barbe, M. T., Tscheuschler, M., Tittgemeyer, M., Siebner, H. R., & Timmermann, L. (2013) · Cerebral Cortex · doi:10.1093/cercor/bht140 · Cited by 48
“These fi ndings are in good agreement with the concept that altered fi ring patterns in basal ganglia lead to abnormal activation of cortical motor areas impairing their respective function (Timmermann et al. 2003; Redgrave et al. 2010).”
BackgroundResultGadziola, M. A., & Wesson, D. W. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.3328-15.2016 · Cited by 52
“To assess whether our head-fixed licking behavior measurement is subject to devaluation and therefore “goaldirected” (Dickinson and Balleine, 1994; Redgrave et al., 2010), a subset of water-restricted animals (n 4) were allowed ad libitum access to water 30 min before testing.”
BackgroundMethodGinis, P., Heremans, E., Ferrari, A., Dockx, K., Canning, C. G., & Nieuwboer, A. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00128 · Cited by 46
RGS9‐2 rescues dopamine D2 receptor levels and signaling in DYT1 dystonia mouse models
Bonsi, P., Ponterio, G., Vanni, V., Tassone, A., Sciamanna, G., Migliarini, S., Martella, G., Meringolo, M., Dehay, B., Doudnikoff, É., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201809283 · Cited by 51
“Striatal dopaminergic transmission is central to movement control and several disease conditions (Redgrave et al, 2010; Gittis & Kreitzer, 2012).”
BackgroundJanssen, S., van Steveninck, J. D. R., Salim, H. S., Cockx, H., Bloem, B. R., Heida, T., & Wezel, R. J. A. V. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00185 · Cited by 52
Complex Population Response of Dorsal Putamen Neurons Predicts the Ability to Learn
Laquitaine, S., Piron, C., Abellanas, D., Loewenstein, Y., & Boraud, T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080683 · Cited by 46
“goal-directed tasks [13].”
Caligiore, D., Borghi, A. M., Parisi, D., Ellis, R., Cangelosi, A., & Baldassarre, G. (2012) · Psychological Research · doi:10.1007/s00426-012-0424-1 · Cited by 47
Hidalgo-Balbuena, A. E., Luma, A. Y., Pimentel-Farfan, A. K., Peña-Rangel, T. M., & Rueda‐Orozco, P. E. (2019) · Nature Communications · doi:10.1038/s41467-019-12075-y · Cited by 53
Nigrostriatal dopamine pathway regulates auditory discrimination behavior
Chen, A. P. F., Malgady, J. M., Chen, L., Shi, K. W., Cheng, E., Plotkin, J. L., Ge, S., & Xiong, Q. (2022) · Nature Communications · doi:10.1038/s41467-022-33747-2 · Cited by 46
The Basal Ganglia Optimize Decision Making over General Perceptual Hypotheses
Lepora, N. F., & GURNEY, K. N. (2012) · Neural Computation · doi:10.1162/neco_a_00360 · Cited by 45
“More recently, this architecture has been revealed as an oversimplification, with significant reciprocal connectivity between the various internal nuclei, including a pathway from STN onto GPe (see Redgrave et al, 2010 ).”
BackgroundGoréa, A. (2011) · Journal of Physiology-Paris · doi:10.1016/j.jphysparis.2011.09.008 · Cited by 47
“These observations are compatible with the observed loss of dopaminergic neurons in the substantia nigra of Parkinson patients (for a review see Redgrave et al., 2010), so that PeDu has been used as a model of BG dysfunction.”
ResultGoetz, L., Piallat, B., Bhattacharjee, M., Mathieu, H., Olivier David, A., & Chabardès, S. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2514-15.2016 · Cited by 46
“Further studies will be needed to investigate whether MRF could be seen as a converging structure on the motor path, as has been hypothesized (Redgrave et al., 2010).”
BackgroundCingulate-basal ganglia-thalamo-cortical aspects of catatonia and implications for treatment
Fricchione, G. L., & Beach, S. R. (2019) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64196-0.00012-1 · Cited by 48
Isaacson, S., Hauser, R. A., Pahwa, R., Gray, D. L., & Duvvuri, S. (2023) · Clinical Parkinsonism & Related Disorders · doi:10.1016/j.prdoa.2023.100212 · Cited by 58
“Dopamine facilitates movement by stimulating the direct (go) pathway and inhibiting the indirect (stop) pathway [31].”
BackgroundBuendia, J. D. J. A., Rueda‐Orozco, P. E., Hernandez-Martinez, R., Plata, V. T. G., Ibáñez-Sandoval, O., Galarraga, E., & Bargas, J. (2011) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2011.00006 · Cited by 44
“SYSTEMS NEUROSCIENCE et al., 1989; Bateup et al., 2010; Kravitz et al., 2010; Redgrave et al., 2010).”
BackgroundSmith, J. B., Mowery, T. M., & Alloway, K. D. (2012) · Journal of Neurophysiology · doi:10.1152/jn.00142.2012 · Cited by 45
“…nuclei. basal ganglia; neuronal tracing; somatosensory; tactile stimulation; thalamostriatal; thalamus SUBSTANTIAL EVIDENCE INDICATES that the striatum is involved in regulating the selection and execution of specific motor behaviors (McHaffie et al. 2005; Redgrave et al. 2010; Smith et al. 2011).”
BackgroundPiramide, N., Agosta, F., Sarasso, E., Canu, E., Volonté, M. A., & Filippi, M. (2020) · Journal of Neurology · doi:10.1007/s00415-019-09687-1 · Cited by 46
“However, it has been hypothesized that visual and auditory cues permit to bypass the executive-attentive network and to organize the motor schemes through less-affected neural circuits [54].”
BackgroundMotivational modulation of bradykinesia in Parkinson’s disease off and on dopaminergic medication
Kojović, M., Mir, P., Trender‐Gerhard, I., Schneider, S. A., Pareés, I., Edwards, M. J., Bhatia, K. P., & Jahanshahi, M. (2014) · Journal of Neurology · doi:10.1007/s00415-014-7315-x · Cited by 45
“could also be considered within the theoretical framework that proposes dual, goal-directed and habitual systems of movement control [28].”
Heremans, E., Nackaerts, E., Vervoort, G., Broeder, S., Swinnen, S. P., & Nieuwboer, A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0148933 · Cited by 44
“As patients with FOG experience an exaggerated automaticity deficit, they may be forced to rely on the goal-directed mode of action, linked to the early phases of learning, even more so than their non-freezing counterparts [33].”
Relearning of Writing Skills in Parkinson's Disease After Intensive Amplitude Training
Nackaerts, E., Heremans, E., Vervoort, G., Smits-Engelsman, B. C. M., Swinnen, S. P., Vandenberghe, W., Bergmans, B. A., & Nieuwboer, A. (2016) · Movement Disorders · doi:10.1002/mds.26565 · Cited by 44
“As the posterior putamen has been associated with control of habitual behavior, it has been put forward that automatically controlled movements in PD are affected, leading to an increased reliance on goal-directed control of movements.(3,4) Handwriting is a complex functional activity incorporating both automated and…”
BackgroundZhao, F., Zeng, Y., & Xu, B. (2018) · Frontiers in Neurorobotics · doi:10.3389/fnbot.2018.00056 · Cited by 44
“It has inhibitory connections with STN and GPi (Redgrave et al., 2010).”
Capato, T., de Vries, N. M., IntHout, J., Barbosa, E. R., Nonnekes, J. H., & Bloem, B. R. (2019) · Journal of Parkinson s Disease · doi:10.3233/jpd-191752 · Cited by 44
“However, it is plausible that the internal and external cueing strategies used in this study, likely had enabled patients to switch from automatic motor control to goal-directed motor control [60].”
ResultIslam, A., Alcock, L., Nazarpour, K., Rochester, L., & Pantall, A. (2020) · npj Parkinson s Disease · doi:10.1038/s41531-020-00119-w · Cited by 44
Brain Motor Network Changes in Parkinson’s Disease: Evidence from Meta-Analytic Modeling
Herz, D., Meder, D., Camilleri, J., Eickhoff, S., & Siebner, H. (2021) · Movement Disorders · doi:10.1002/mds.28468 · Cited by 44
“It has previously been suggested that PD patients might rely more on effortful or “goal-directed” behavior, which is related to the associative cortical–basal ganglia loop, because more “automatic” motor behavior, which has been related to the motor cortical–basal ganglia loop, is impaired.(84) Similarly, it has been…”
BackgroundManagement of freezing of gait — mechanism-based practical recommendations
Tosserams, A., Fasano, A. A., Gilat, M., Factor, S. A., Giladi, N., Lewis, S. J. G., Moreau, C., Bloem, B. R., Nieuwboer, A., & Nonnekes, J. H. (2025) · Nature Reviews Neurology · doi:10.1038/s41582-025-01079-6 · Cited by 43
“This anterior motor circuit is involved in goal-directed motor control, so it provides a mechanism to compensate for the loss of automatic gait control 41 .”
A Preclinical Study Evaluating AAVrh10-Based Gene Therapy for Sanfilippo Syndrome
Winner, L. K., Beard, H., Hassiotis, S., Lau, A. A., Luck, A. J., Hopwood, J. J., & Hemsley, K. M. (2016) · Human Gene Therapy · doi:10.1089/hum.2015.170 · Cited by 45
“21,23 Of important note is that, in a rat study, AAVrh10 evades preexisting immunity to the common AAV serotypes naturally infecting humans (AAV 1, 2, and 5).”
Négrini, S., Bissolotti, L., Ferraris, A., Noro, F., Bishop, M. D., & Villafañe, J. H. (2016) · Journal of Bodywork and Movement Therapies · doi:10.1016/j.jbmt.2016.06.001 · Cited by 43
The effects of early‐life stress on dopamine system function in adolescent female rats
Majcher‐Maślanka, I., Solarz, A., Wędzony, K., & Chocyk, A. (2017) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2017.01.001 · Cited by 44
Levodopa response differs in Parkinson's motor subtypes: A task‐based effective connectivity study
Mohl, B., Berman, B. D., Shelton, E., & Tanabe, J. (2017) · The Journal of Comparative Neurology · doi:10.1002/cne.24197 · Cited by 43
“In other words, neural signals propagating to or originating from the putamen in PIGD patients are not being relayed to the major output pathways of the basal ganglia (globus pallidus interna and substantia nigra pars reticulate), on to the thalamus, and back to the cortex (Redgrave et al., 2010).”
BackgroundStuart, S., Galna, B., Delicato, L. S., Lord, S., & Rochester, L. (2017) · European Journal of Neuroscience · doi:10.1111/ejn.13589 · Cited by 43
“Redgrave et al. (2010) highlighted that motor control impairment occurs early in PD and requires attentional effort to overcome the loss of automatic movement, particularly when performing complex motor tasks (i.e. a turn when walking).”
The relationship between apathy and impulsivity in large population samples
Petitet, P., Scholl, J., Attaallah, B., Drew, D., Manohar, S., & Husain, M. (2021) · Scientific Reports · doi:10.1038/s41598-021-84364-w · Cited by 47
The Myelin‐Weighted Connectome in Parkinson's Disease
Boshkovski, T., Cohen‐Adad, J., Mišić, B., Arnulf, I., Corvol, J., Vidailhet, M., Lehéricy, S., Stikov, N., & Mancini, M. (2021) · Movement Disorders · doi:10.1002/mds.28891 · Cited by 41
“This is in line with the motor symptoms caused by the disease, because the putamen is linked to motor performance, as it has been shown previously.(80) Other connections that also negatively covaried with the motor score were identified between the thalamus and the paracentral lobule and postcentral gyrus, which is al…”
ResultKucinski, A. J., Albin, R. L., Lustig, C., & Sarter, M. F. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.01.012 · Cited by 42
Cognitive control and the dopamine D2-like receptor: a dimensional understanding of addiction
Groman, S. M., & Jentsch, J. D. (2011) · Depression and Anxiety · doi:10.1002/da.20897 · Cited by 43
“[52] The topographical organization is retained in the striatal projections to the pallidum and substantia nigra, which finally relay back to the cortex via the thalamus.[53] Because of these parallel looping projections, neural signals embedded in this circuit are susceptible to modulation at any of these points and…”
BackgroundSuppa, A., Bologna, M., Conte, A., Berardelli, A., & Fabbrini, G. (2016) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2016.1219251 · Cited by 42
Subthalamic Nucleus Neurons Differentially Encode Early and Late Aspects of Speech Production
Lipski, W. J., Alhourani, A., Pirnia, T., Jones, P., Dastolfo‐Hromack, C., Helou, L. B., Crammond, D. J., Shaiman, S., Dickey, M. W., Holt, L. L., et al. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.3480-17.2018 · Cited by 43
“This balance of basal ganglia-mediated activation and suppression has been understood most frequently in terms of either selecting and focusing motor actions (Mink, 1996; Redgrave et al., 2010), or modulating their gain over time (Alexander and Crutcher, 1990a; Nambu et al.”
BackgroundRemote Monitoring of Treatment Response in Parkinson's Disease: The Habit of Typing on a Computer
Matarazzo, M., Arroyo‐Gallego, T., Montero, P., Puertas‐Martín, V., Butterworth, I., Mendoza, C. S., Ledesma‐Carbayo, M. J., Catalán, M. J., Molina, J. A., Bermejo‐Pareja, F., et al. (2019) · Movement Disorders · doi:10.1002/mds.27772 · Cited by 44
Ferrazzoli, D., Ortelli, P., Cucca, A., Bakdounes, L., Canesi, M., & Volpe, D. (2020) · Neurodegenerative Disease Management · doi:10.2217/nmt-2019-0025 · Cited by 42
Patient-Derived Midbrain Organoids to Explore the Molecular Basis of Parkinson's Disease
Galet, B., Cheval, H., & Ravassard, P. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.01005 · Cited by 47
LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson's disease
Chang, E. E. S., Ho, P. W., Liu, H., Pang, S. Y.-Y., Leung, C.-T., Malki, Y., Choi, Z. Y.-K., Ramsden, D. B., & Ho, S. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00285-2 · Cited by 45
Normative data for arm swing asymmetry: How (a)symmetrical are we?
Plate, A., Sedunko, D., Pelykh, O., Schlick, C., Ilmberger, J., & Bötzel, K. (2014) · Gait & Posture · doi:10.1016/j.gaitpost.2014.07.011 · Cited by 41
“The reduced arm swing during gait, which initially appears one-sided, might be one of the first motor symptoms because subconscious movement generation relies heavily on intact dopaminergic innervation [2].”
BackgroundImaging analysis of Parkinson’s disease patients using SPECT and tractography
Son, S.-J., Kim, M., & Park, H. (2016) · Scientific Reports · doi:10.1038/srep38070 · Cited by 43
Kovaleski, R. F., Callahan, J. W., Chazalon, M., Wokosin, D. L., Baufreton, J., & Bevan, M. D. (2020) · The Journal of Physiology · doi:10.1113/jp279232 · Cited by 39
“…positioned network within the basal ganglia, a group of subcortical brain nuclei critical for the execution of motivated, goal-directed, and habitual behaviours (Mink & Thach, 1993; Yin & Knowlton, 2006; Redgrave et al. 2010; Keeler et al. 2014; Nelson & Kreitzer, 2014; Klaus et al. 2019).”
BackgroundShin, J. H., Song, M. J., Paik, S., & Jung, M. W. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2010361117 · Cited by 43
Bichsel, O., Gassert, R., Stieglitz, L. H., Uhl, M., Baumann‐Vogel, H., Waldvogel, D., Baumann, C. R., & Imbach, L. (2018) · NeuroImage · doi:10.1016/j.neuroimage.2018.05.012 · Cited by 40
Dopaminergic Vulnerability in Parkinson Disease: The Cost of Humans’ Habitual Performance
Hernández, L. F., Obeso, I., Costa, R. M., Redgrave, P., & Obeso, J. A. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.03.007 · Cited by 40
The Evolution-Driven Signature of Parkinson’s Disease
Diederich, N. J., Uchihara, T., Grillner, S. E., & Goetz, C. G. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.05.001 · Cited by 39
“The tasks of the striatum are challenging, as it integrates external and internal information [6,39,40], with an enormous convergence of synaptic connections from almost every region of the cerebral cortex onto striatal projection neurons (SPNs) [41].”
Bichsel, O., Stieglitz, L. H., Oertel, M. F., Baumann, C. R., Gassert, R., & Imbach, L. (2021) · Scientific Reports · doi:10.1038/s41598-021-87031-2 · Cited by 40
Pieruccini‐Faria, F., Martens, K. A. E., Silveira, C. R. A., Jones, J. A., & Almeida, Q. J. (2014) · BMC Neurology · doi:10.1186/s12883-014-0250-8 · Cited by 40
“Additionally, our results are in line with recent theory, supporting the notion that individuals with PD operate in an attention-controlled mode due to an abnormal sensorimotor processing within basal ganglia loops [15].”
BackgroundResultMongeon, D., Blanchet, P. J., & Messier, J. (2013) · Brain and Cognition · doi:10.1016/j.bandc.2012.12.001 · Cited by 39
Korb, F. M., Jiang, J., King, J. A., & Egner, T. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.3289-16.2017 · Cited by 48
“…RTs) in this protocol is commensurate with a role for the BG as representing a final response selection pathway (Mink, 1996; Grillner et al., 2005; Redgrave et al., 2010), and as being involved in delaying responding under conditions of decision conflict (Frank et al., 2007), here under…”
BackgroundResultInfluentialSgroi, S., & Tonini, R. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00524 · Cited by 39
Harischandra, D. S., Rokad, D., Ghaisas, S., Verma, S., Robertson, A., Jin, H., Anantharam, V., Kanthasamy, A., & Kanthasamy, A. G. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.165533 · Cited by 39
“Dopaminergic neurons in the mid-brain region are the main source of the neurotransmitter dopamine, which regulates multiple brain functions including voluntary movement and a broad array of behavioral processes such as mood, reward, addiction, and stress [1, 2].”
BackgroundNavigating complex decision spaces: Problems and paradigms in sequential choice.
Walsh, M. M., & Anderson, J. R. (2013) · Psychological Bulletin · doi:10.1037/a0033455 · Cited by 41
“Reinforcement learning has been applied to the study of psychological disorders (Maia & Frank, 2011; Redgrave et al., 2010; Redish, Jensen, & Johnson, 2008).”
MethodBDNF Val66Met and reward-related brain function in adolescents: role for early alcohol consumption
Nees, F., Witt, S. H., Dinu-Biringer, R., Lourdusamy, A., Tzschoppe, J., Vollstädt‐Klein, S., Millenet, S., Bach, C., Poustka, L., Banaschewski, T., et al. (2015) · Alcohol · doi:10.1016/j.alcohol.2014.12.004 · Cited by 41
Ferrazzoli, D., Carter, A., Üstün, F. S., Palamara, G., Ortelli, P., Maestri, R., Yücel, M., & Frazzitta, G. (2016) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2016.00121 · Cited by 40
“The loss of the physiological dopaminergic modulation alters the cortico-striatal plasticity and transforms the basal ganglia into a disruptive filter (Beeler et al., 2013) that impairs the ability to acquire and express habitual-automatic movements (Redgrave et al., 2010).”
BackgroundBeck, E. N., Intzandt, B., & Almeida, Q. J. (2017) · Neurorehabilitation and neural repair · doi:10.1177/1545968317746782 · Cited by 37
Alterations in white matter network topology contribute to freezing of gait in Parkinson’s disease
Hall, J. M., Shine, J. M., Martens, K. A. E., Gilat, M., Broadhouse, K. M., Szeto, J. Y. Y., Walton, C. C., Moustafa, A. A., & Lewis, S. J. G. (2018) · Journal of Neurology · doi:10.1007/s00415-018-8846-3 · Cited by 42
Jenson, D., Reilly, K. J., Harkrider, A. W., Thornton, D. M., & Saltuklaroglu, T. (2018) · NeuroImage Clinical · doi:10.1016/j.nicl.2018.05.026 · Cited by 38
“However, as sensorimotor control is under basal ganglia influence (Redgrave et al., 2010), future studies sensitive to changes in speech timing are necessary to delineate the contributions of sensorimotor and basal ganglia loops to the observed trait-related differences in μ-β activity.”
Sensorimotor subthalamic stimulation restores risk‐reward trade‐off in Parkinson's disease
Irmen, F., Horn, A., Meder, D., Neumann, W., Plettig, P., Schneider, G., Siebner, H. R., & Kühn, A. A. (2018) · Movement Disorders · doi:10.1002/mds.27576 · Cited by 38
Test-Retest Reliability of Dual-Task Outcome Measures in People With Parkinson Disease
Strouwen, C., Molenaar, E., Keus, S. H. J., Münks, L., Bloem, B. R., & Nieuwboer, A. (2016) · Physical Therapy · doi:10.2522/ptj.20150244 · Cited by 39
Fiore, V. G., Sperati, V., Mannella, F., Mirolli, M., GURNEY, K. N., Friston, K. J., Dolan, R. J., & Baldassarre, G. (2014) · Frontiers in Psychology · doi:10.3389/fpsyg.2014.00124 · Cited by 38
Lin, J., & Nardocci, N. (2016) · Frontiers in Neurology · doi:10.3389/fneur.2016.00226 · Cited by 37
Metadata
- Authors
- Redgrave, P., Rodriguez, M., Smith, Y., Rodriguez-Oroz, M. C., Lehericy, S., Bergman, H., Agid, Y., DeLong, M. R., & Obeso, J. A.
- Affiliations
- University of Sheffield (GB)
- Emory University (US)
- Hebrew University of Jerusalem (IL)
- Institut du Cerveau (FR)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Corresponding author
- Redgrave, Peter
- Obeso, Jose A.
- Venue
- Nature reviews. Neuroscience
- Published
- 2010-10-14
- Volume
- 11
- Issue
- 11
- Pages
- 760-772
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- PMC
- PMC3124757
- OpenAlex
- W2056061278
- Cited by
- 1,134
- References
- 178
- Citations by year
- 2026: 59 · 2025: 78 · 2024: 74 · 2023: 70 · 2022: 90 · 2021: 78 · 2020: 75 · 2019: 122 · 2018: 64 · 2017: 62 · 2016: 73 · 2015: 65 · 2014: 72 · 2013: 68 · 2012: 47
- FWCI
- 6.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (091409)
- Universidad de Navarra
- Topics
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- basal ganglia, Parkinson's disease, goal-directed behavior, habitual behavior, dopamine depletion, posterior putamen, action control
- MeSH terms
- Animals, Basal Ganglia, Goals, Habituation, Psychophysiologic, Humans, Models, Neurological, Nerve Net, Neural Pathways, Parkinson Disease
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