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

“Accordingly, the direct projections between the striatum and the basal ganglia output nuclei represent the internal component of the general, partially segregated, looped architecture that connects the basal ganglia with extrinsic cortica”

“The activity of striatal medium spiny projection neurons is conveyed to the output nuclei (GPi and SNr) through a monosynaptic GABA (γ-aminobutyric acid)-ergic projection (the 'direct' pathway) and a polysynaptic ('indirect') pathway that involves relays in the external globus pallidus (GPe) and the subthalamic nucleu…”

“Consequently, according to this model, in the normal state, activation of the 'indirect circuits' at the level of the striatum would promote movement inhibition or arrest, whereas activation of the 'direct circuit' would facilitate movemen”

“However, sensory input is equally important for goal-directed contro”

“In the parkinsonian state , reduced dopamine input from the SNc to the striatum would have a dual effect, facilitating neurons that give rise to the 'indirect' projection and reducing the activation of 'direct pathway' neuron”

“Another study has found that the restoration of SMA activation with apomorphine (a dopamine agonist) was associated with the concomitant improvement of akinesia and bradykinesia (Jenkins et al., 1992).”

“Damage to the putamen is associated with loss of habitual behavior, forcing patients into a goal-directed type of behavior.(91) It is likely that disconnection of the putamen during anesthesia perturbs basal ganglia action selection, contributing to anesthesia-induced spontaneous unresponsiveness by acting in concert…”

“These grouped inputs can be organized into channels subserving sensorimotor, cognitive, and affective functions (Redgrave et al 2010).”

“Although there are rich structural and functional interactions between these loops (28, 30, 31), their topography can be defined in terms of stereotypic projection fields between different components of the cortex, striatum, pallidum, and thalamus (29).”

“The accumbens nucleus has been associated with emotional/ motivational functions of the striatum [90] and is closely connected to limbic structures (amygdala, hippocampus) as well as the prefrontal neocortex [40].”

“In contrast to the associative circuits in the striatum, which mediate goal-directed behavior, the caudolateral sensory motor circuits in the putamen that mediate habitual responses are more prone to neurodegeneration in patients with PD, especially in the earlier stages of the disease.(50) Thus, patients with PD have…”

“Having said this, cortical– basal ganglia loops outputs involve the thalamus (Herrero et al., 2002; Redgrave et al., 2010)—in this context, a modulatory effect mediated by basal ganglia would be accounted for by a change in corticothalamic interactions our model.”

“The BG receiving territory of Mthal is thus ideally situated to be involved in motor learning because of its connections with prefrontal cortex and premotor cortex (McFarland and Haber, 2002; Xiao et al., 2009; Redgrave et al., 2010).”

“PD is characterized by progressive loss of dopaminergic cells in the substantia nigra and dopamine depletion in the striatum, which lead to dysfunction in corticostriatal networks that are essential for control of movement and cognition.(3) In early PD, the posterior putamen is heavily affected by dopamine depletion,…”

“There are multiple ways this can be realized, and mounting evidence indicates model-based and model-free forms of reinforcement learning (RL) contribute to behavioral control (Balleine and O’Doherty, 2010; Boureau and Dayan, 2011; Daw et al., 2005; Doya, 1999; Redgrave et al., 2010; Wunderlich et al., 2012).”

“The connection from the STN to M1 was inhibitory, in accordance with animal models in which the basal ganglia exert an inhibitory influence over thalamocortical structures (Redgrave et al., 2010).”

“It has recently been argued that the progressive loss of dopamine in the posterior putamen (the region that controls habitual action) that is a pathological hallmark of Parkinson’s disease might force patients to rely on goal-directed processes of action control [64].”

“…basal ganglia function, which propose that the motor network uses striatal regions responsible for habitual functions, relying on the CCN and its interaction with more rostral striatal regions (such as the caudate and the ventral striatum) to accomplish goal-directed tasks (Redgrave et al., 2010).”

“These results are largely consistent with previous studies suggesting that different parts of the basal ganglia support " goal-directed behavior " and " habits " (Redgrave et al 2010; Yin & Knowlton 2006).”

“External cues trigger goal-directed behaviour that is better performed, which bypasses the defective basal ganglia (Redgrave et al., 2010).”

“The CM/Pf complex also receives significant afferents from various subcortical sources, including the superior colliculus (Grunwerg et al., 1992; Redgrave et al., 2010), the pedunculopontine tegmental nucleus (Pare et al.”

“Regions within the cognitive control network are known to co-activate with other neural networks to mediate goal-directed behaviour (Spreng et al., 2010) and recent research has implicated the basal ganglia in the mediation of these capacities (Bartels et al., 2006; Redgrave et al., 2010).”

“clinical, animal lesion, and physiological studies suggest that different regions of the basal ganglia are involved in controlled versus automatic behavior (Ashby and Maddox, 2005; Balleine and O’Doherty, 2010; Hikosaka et al., 1999; Redgrave et al., 2010; Yin and Knowlton, 2006).”

“Dopamine (DA)-releasing neurons in the mammalian midbrain play an important role in fundamental behaviors, including motivation, reinforcement learning and motor control, and their dysfunction is associated with a wide range of neuropsychiatric disorders (Wise, 2004; Costa, 2007; Schultz, 2007; Morris et al., 2009; Re…”

“the cortex and subcortex is critical given evidence that these brain systems are known to function (Redgrave et al. 2010), develop (Raznahan et al.”

“…connectivity between PFC and BG during implementation is weakest when IC is expected (Jahfari et al., 2012), presumably because the action control network (Frank et al., 2001; Redgrave et al., 2010; Majid et al., 2013; including the putamen and the BG more broadly) has been proactively prepared.”

“Second, dysfunctions of automatic processes (rather than voluntary process) could cause switching deficits if the switching involves an automatic process (Koerts et al., 2009; Redgrave et al., 2010).”

“As a consequence, a shift in neural activation from subcortical to more cortical areas (i.e., more reliance on controlled processes) can be expected as a compensation strategy (Redgrave et al., 2010).”

“FOG disappears when patients shift from an automatic control of gait toward a more goal-directed one.(8,9) In”

“The increased STN gamma band activity observed in these studies may reflect the switch from automatic to controlled processing on these attention- and resource-demanding cognitive tasks, consistent with the proposal that the STN implements a signal from the prefrontal cortex to switch from automatic to controlled proc…”

“Given the broad patterns of cortical projections to the basal ganglia, it is not surprising that the basal ganglia are associated with a large variety of functions, including motor control (Redgrave et al., 2010), cognitive coordination (Stocco et al.”

“Tonic DA has a pivotal role in enhancing the performance of motor behavior, as shown by the impairment of motor behavior in Parkinson patients after its decrease in sensorimotor regions of striatum (Redgrave et al., 2010).”

“4 positioned to participate in evidence accumulation as part of its established role in action selection (Bogacz and Gurney, 2007; Graybiel, 2008; Hikosaka et al., 2014; Jin and Costa, 2010; Nelson and Kreitzer, 2014; Redgrave et al., 2010).”

“As predicted from our data, people with Parkinson’s disease often have difficulties in performing daily routines automatically (Kim and Hikosaka, 2015; Redgrave et al., 2010).”

“…pathways are based on tracer studies in primates showing that the GPi is connected to the motor cortex (via the ventrolateral anterior nucleus of the thalamus; Hoover and Strick, 1999; Redgrave et al., 2010) and that the STN is connected to the cerebellar cortex (via the pons; Bostan et al., 2010).”

“Integrating dopaminergic inputs and glutamatergic inputs from sensorimotor cortical regions (McGeorge and Faull, 1987), the striatum is poised to control movement and decision-making (Redgrave et al., 2010).”

“Theoretical questions regarding human planning [2], reasoning [3], development [4], voluntary-control [5], learning under uncertainty [6], motor control [7], and deployment of attentional resources [8], all invoke this dichotomy.”

“Second, their inclusion allows us to model the three major pathways connecting motor cortex and basal ganglia (direct pathway, indirect pathway, hyperdirect pathway) (Redgrave et al., 2010).”

“Evidence from animal studies highlight the complexity in functional organization of the cortico-striatalthalamic circuitry, which, however, is beyond the scope of this review.(34) Here, we will only focus on a simplified model of the direct and indirect pathways, which includes the striatum whose function is known to…”

“The basal ganglia are an ensemble of subcortical nuclei that are critically involved in control of action (Albin et al., 1995; Graybiel, 2008; Redgrave et al., 2010; Turner & Desmurget, 2010; Costa, 2011; Gerfen & Surmeier, 2011; Kravitz et al., 2012).”

“Although initially considered a motor disease, more and more researchers see it today as a malfunctioning of the motivational system (Redgrave et al. 2010).”

“Our findings correspond with these studies insofar as they also demonstrate alterations to network functional dynamics, in this case within the cortico–basal ganglia thalamocortical system in PD.(2,3) In addition to decreases already described for cortical-subcortical connectivity, significant functional deficits were…”

“2007] in line with the preferential degeneration of dopaminergic neurons in the caudal and lateral SN in histological studies [Redgrave et al. 2010].”

“…learning, habit formation, goal-directed action selection and exploration (Chase et al., 2004; Balleine and O'Doherty, 2009; Jin and Costa, 2010; Redgrave et al., 2010; Costa, 2011; Schiemann et al., 2012; Everitt and Robbins, 2013) while neighboring VTA DA neurons, with axonal projections to…”

“[26] as well as during goal-directed behavior [27].”

“, 1997), the explicit role of dopamine in controlling actions remains poorly understood (Jin and Costa, 2010; Kim et al., 2015; Matsumoto and Hikosaka, 2009; Redgrave and Gurney, 2006; Redgrave et al., 2010).”

“In Parkinson’s disease, the self-observation characterizing the BMI paradigm seems particularly appealing to experimentally test the provocative hypothesis of a specific loss of habitual control versus goal-directed control (Redgrave et al., 2010) and to elucidate its underlying neural mechanisms.”

“’’ The segregation between goal-directed behavior (mediated by frontal-associative basal ganglia-thalamic loops) and stimulus-response habitual behavior (mediated by sensorimotor cortex-sensorimotor basal ganglia-thalamic loops) is an increasingly important concept, recently extended to provide a pathophysiological mo…”

“Thus, dopamine seems to differentially impact upon motor control loops in the parkinsonian brain (Redgrave et al., 2010; Jenkinson and Brown, 2011).”

“Anterior insula and anterior cingulate cortex detect salient stimuli and initiate executive control (Menon and Uddin, 2010) whilst the basal ganglia regulate the information flow into working memory and the selection of goal-directed responses via inhibitory feedback loops (Gurney et al., 2001a, 2001b; McNab and Kling…”

“…action of the net excitatory direct basal ganglia pathway, which predominantly expresses dopamine D1 family receptors, and the net inhibitory indirect basal ganglia pathway, which expresses dopa- mine D2 family receptors (Gerfen, 1992, 2000; Surmeier et al., 1998; Redgrave et al., 2010).”

“In other words, the price we pay for our highly developed neocortex and its associated advanced cognitive and behavioral possibilities is the demand to contend with the overwhelming selection problem it generates [54, 55].”

“These findings are in accordance with early PD symptomatic description, as executive function, attention deficit and episodic and procedural memory impairment have been described (20, 64, 115, 160, 162, 204).”

“The striatum plays a key role in controlling goal-directed movements and habits (Graybiel and Grafton, 2015; Redgrave et al., 2010).”

“Based on these results and on further evidence for goal-directed control in the basal ganglia (Redgrave et al., 2010), a tentative interpretation of our finding is that the selective functions of the motor cingulate–basal ganglia circuit which enable associative motor learning are primarily…”

“First, as described above and elsewhere (e.g., Redgrave et al., 2010), the direct and indirect pathway architecture offers an incomplete description of the complex intrinsic basal ganglia circuitry.”

“This model is consistent with the finding that PD patients experience difficulty in performing volitional movements (Lang and Lozano, 1998; Dauer and Przedborski, 2003; Fahn, 2003; Redgrave et al., 2010).”

“In fact, PD patients have a decreased capacity to engage in normal automatic (habitual) control of actions, and become increasingly dependent on a goal-directed mode of action, which impedes their normal daily activities (see Redgrave et al., 2010b for a review).”