Adaptive Functions of the Corpus Striatum: The Past and Future of the R-Complex

The basal ganglia is emerging from the shadow cast by the most conspicuous clinical expression of its dysfunction: motor disorders.What is revealed is the nexus of a widely distributed system which functions in integrating action with cognition, motivation, and affect. Prominent among non-motor functions are striatal involvement in building up of sequences of behavior into meaningful, goal-directed patterns and repertoires and the selection of appropriate learned or innate sequences in concert with their possible predictive control. Further, striatum seems involved in declarative and strategic memory (involving intentional recollection and the management of retrieved memories, respectively). Findings from reptile experiments indicate striatal control over specific assemblies of innate units of behavior that involve autonomic modulation. Its involvement in the appropriate expression of species-typical action patterns in reptiles and primates provides an interesting vantage point from which to interpret its involvement in the assembly of units of behavior into specific adaptive behavioral patterns. For the current version with updated commentary, see https://notes.utk.edu/bio/greenberg.nsf/9e9a470d5230cdda852563ef0059fa56/89b6c6545b8412c185256a2c0060b638?OpenDocumen

A model of reversal learning and working memory in medicated and unmedicated patients with Parkinsons disease

Wepresent a neural network model of cognition in medicated and unmedicated patients with Parkinson’s disease (PD) in various learning and memory tasks. The model extends our prior models of the basal ganglia and PD with further modeling of the role of prefrontal cortex (PFC) dopamine in stimulus–response learning, reversal, and working memory. In our model, PD is associated with decreased dopamine levels in the basal ganglia and PFC, whereas dopamine medications increase dopamine levels in both brain structures. Simulation results suggest that dopamine medications impair stimulus–response learning in agreement with experimental data (Breitenstein et al., 2006; Gotham, Brown, & Marsden, 1988). Weshow how decreased dopamine levels in the PFC in unmedicated PD patients are associated with impaired working memory performance, as seen experimentally (Costa et al., 2003; Lange et al., 1992; Moustafa, Sherman, & Frank, 2008; Owen, Sahakian, Hodges, Summers, & Polkey, 1995). Further, our model simulations illustrate how increases in tonic dopamine levels in the PFC due to dopamine medications will enhance working memory, in accord with previous modeling and experimental results (Cohen, Braver, & Brown, 2002; Durstewitz, Seamans, & Sejnowski, 2000; Wang, Vijayraghavan, & Goldman-Rakic, 2004). The model is also consistent with data reported in Cools, Barker, Sahakian, and Robbins (2001), who showed that dopamine medications impair reversal learning. In addition, our model shows that extended training of the reversal phase leads to enhanced reversal performance in medicated PD patients, which is a new, and as yet untested, prediction of the model. Overall, our model provides a unified account for performance in various behavioral tasks using common computational principles.Research reported in this publication was supported by National Institutes of Health Award 1 P50 NS 071675-02 from the National Institute of Neurological Disorders and Stroke and by a 2013 internal UWS Research Grant Scheme award P00021210 to A.A.M

The role of prediction and outcomes in adaptive cognitive control

Humans adaptively perform actions to achieve their goals. This flexible behaviour requires two core abilities: the ability to anticipate the outcomes of candidate actions and the ability to select and implement actions in a goal-directed manner. The ability to predict outcomes has been extensively researched in reinforcement learning paradigms, but this work has often focused on simple actions that are not embedded in hierarchical and sequential structures that are characteristic of goal-directed human behaviour. On the other hand, the ability to select actions in accordance with high-level task goals, particularly in the presence of alternative responses and salient distractors, has been widely researched in cognitive control paradigms. Cognitive control research, however, has often paid less attention to the role of action outcomes. The present review attempts to bridge these accounts by proposing an outcome-guided mechanism for selection of extended actions. Our proposal builds on constructs from the hierarchical reinforcement learning literature, which emphasises the concept of reaching and evaluating informative states, i.e., states that constitute subgoals in complex actions. We develop an account of the neural mechanisms that allow outcome-guided action selection to be achieved in a network that relies on projections from cortical areas to the basal ganglia and back-projections from the basal ganglia to the cortex. These cortico-basal ganglia-thalamo-cortical ‘loops’ allow convergence – and thus integration – of information from non-adjacent cortical areas (for example between sensory and motor representations). This integration is essential in action sequences, for which achieving an anticipated sensory state signals the successful completion of an action. We further describe how projection pathways within the basal ganglia allow selection between representations, which may pertain to movements, actions, or extended action plans. The model lastly envisages a role for hierarchical projections from the striatum to dopaminergic midbrain areas that enable more rostral frontal areas to bias the selection of inputs from more posterior frontal areas via their respective representations in the basal ganglia.This work is supported by the Biotechnology and Biological Sciences Research Council (BBSRC) Grant BB/I019847/1, awarded to NY and FW

Impulsivity and compulsivity are differentially associated with automaticity and routine on the Creature of Habit Scale.

Habits may develop when meaningful action patterns are frequently repeated in a stable environment. We measured the differing tendencies of people to form habits in a population sample of n = 533 using the Creature of Habit Scale (COHS). We confirmed the high reliability of the two latent factors measured by the COHS, automaticity and routines. Whilst automatic behaviours are triggered by context and do not serve a particular purpose or goal, routines often have purpose, and because they have been performed so often in a given context, they become automatic only after their action sequence has been activated. We found that both types of habitual behaviours are influenced by the frequency of their occurrence and they are differentially influenced by personality traits. Compulsive personality is associated with an increase in both aspects of habitual tendency, whereas impulsivity is linked with increased automaticity, but reduced routine behaviours. Our findings provide further evidence that the COHS is a useful tool for understanding habitual tendencies in the general population and may inform the development of therapeutic strategies that capitalise on functional habits and help to treat dysfunctional ones

The role of frontal cortical-basal ganglia circuits in simple and sequential visuomotor learning

Imaging, recording and lesioning studies implicate the basal ganglia and anatomically related regions of frontal cortex in visuomotor learning. Two experiments were conducted to elucidate the role of frontal cortex and striatum in visuomotor learning. Several tasks were used to characterize motor function including: a visuomotor reaction time (VSRT) task, measuring response speed and accuracy to luminance cues; simple stimulus-response (S-R) learning, measuring VSRT improvements when cues occurred in consistent locations over several trials; and a serial reaction time (SRT) task measuring motor sequence learning. SRT learning was characterized by incremental changes in reaction time (RT) when trained with the same sequence across daily sessions and by abrupt RT changes when switched to random sequence sessions. In experiment 1, rats with excitotoxic lesions in primary (M1) or secondary (M2) motor cortex, primary and secondary (M1M2) motor cortices, medial prefrontal cortex (mPF) or sham surgery were tested on these tasks. Cortical lesions slowed RT in the VSRT task but did not impair short- or long-term simple S-R learning. Cortical lesions increased RTs for the initial response of a 5-response sequence in the SRT task that was exacerbated when performing repeated (learned) sequences. All groups demonstrated visuomotor sequence learning including incremental changes in RTs for later responses in learned sequences that reversed abruptly when switched to random sequences. Rats in experiment 2 were given lesions in dorsolateral striatum, dorsomedial striatum, complete dorsal striatum, ventral striatum and sham surgery. Rats with ventral striatal lesions were unimpaired on any visuomotor task demonstrating shorter RTs than controls on most measures. Dorsomedial striatal lesions significantly impaired all VSRT performance measures. Striatal lesions had no effect on short or long-term simple S-R learning. Lesions involving dorsomedial striatum disrupted initiation of motor sequences in the SRT task. This impairment was exaggerated when performing well-learned sequences. Striatal lesions did not disrupt the incremental RT changes of later responses in the sequence indicative of motor learning. Results suggest that cortico-striatal circuits are involved in initiating learned motor sequences consistent with a role in motor planning. These circuits do not appear essential for acquisition or execution of learned visuomotor sequences

The neurocognition of developmental disorders of language

Developmental disorders of language include developmental language disorder, motor-speech disorders such as articulation disorder and stuttering, and dyslexia. These disorders have been explained by various accounts, which generally focus on their behavioral rather than neural characteristics, their processing rather than learning impairments, and each disorder separately rather than together, despite their commonalities and comorbidities. Here we update and review a unifying neurocognitive account, the Procedural circuit Deficit Hypothesis (PDH). The PDH posits that abnormalities of brain structures underlying procedural memory (learning and memory that relies on the basal ganglia and associated circuitry) can explain numerous brain and behavioral characteristics, across learning and processing, in multiple disorders, including both commonalities and differences. We describe procedural memory, examine its role in multiple aspects of language, and then present the PDH and relevant evidence across language-related disorders. The PDH has substantial explanatory power, and both basic research and translational implications

The role of ventrolateral prefrontal cortex in performance of spatial self-ordered response sequences in the marmoset

The ventrolateral prefrontal cortex (vlPFC) in primates plays an important role in cognitive control and working memory, but as argued in the Introduction its contribution to those aspects of goal-directed behaviour such as planning and executing spatial response sequences requires further analysis, using more refined methods than have been employed hitherto. These studies investigated the role of vlPFC in performance of self-ordered response sequences using intra-cerebral microinfusions of specific pharmacologic agents in the common marmoset. Following a description of the necessary methodology, including behavioural training and surgical details (Chapter 2), a causal role for vlPFC in performance of spatial-self ordered sequences was confirmed in Chapter 3 by demonstrating that local inactivation of vlPFC using muscimol/baclofen infusions impairs sequencing. This effect was shown to be selective to performance of sequences that varied spatially from trial to trial; thus, no effects of vlPFC inactivation were observed for performance of a fixed response sequence. Once animals could learn a heuristical strategy for a self-ordered fixed sequence, vlPFC inactivation no longer impaired performance. Chapter 4 investigated the effects of the chemical neuromodulation of vlPFC on self-ordered sequencing using microinfusions of dopamine receptor D2 antagonist, sulpiride, and 5HT2A receptor antagonist, M100907 on performance of variable sequences. These drugs produced contrasting, dose-dependent impairments. M100907 impaired accuracy, while sulpiride impaired error correction. Chapter 5 studied effects of blocking glutamatergic receptors in a region of the caudate nucleus to which the vlPFC projects, but no significant effects on sequencing accuracy were observed, although there were large effects on perseverative errors in 2 out of 3 animals. The findings are discussed in Chapter 6 in terms of the functioning of the vlPFC and its possible role in controlling flexible response sequencing and working memory. The findings are shown to be of relevance for psychiatric disorders such as obsessive compulsive disorder (OCD) and schizophrenia, which show functional dysconnectivity of the vlPFC in association with response sequencing impairments

Working memory training mostly engages general-purpose large-scale networks for learning

The present meta-analytic study examined brain activation changes following working memory (WM) training, a form of cognitive training that has attracted considerable interest. Comparisons with perceptual-motor (PM) learning revealed that WM training engages domain-general large-scale networks for learning encompassing the dorsal attention and salience networks, sensory areas, and striatum. Also the dynamics of the training-induced brain activation changes within these networks showed a high overlap between WM and PM training. The distinguishing feature for WM training was the consistent modulation of the dorso- and ventrolateral prefrontal cortex (DLPFC/VLPFC) activity. The strongest candidate for mediating transfer to similar untrained WM tasks was the frontostriatal system, showing higher striatal and VLPFC activations, and lower DLPFC activations after training. Modulation of transfer-related areas occurred mostly with longer training periods. Overall, our findings place WM training effects into a general perception-action cycle, where some modulations may depend on the specific cognitive demands of a training task.Peer reviewe

The role of frontal-striatal circuits in instrumental behaviour

Behaviour can be goal-directed, when performing an action to obtain a specific goal, and it can be habitual, whereby a stimulus in the environment can trigger a response regardless of the outcome. Behavioural output can be a mixture of goal-directed and habitual aspects and there may be a competitive balance between these dual influences. Degrading contingencies between actions (A) and their outcomes (O) challenges beliefs about cognitive control and can be used to distinguish between behaviour that is goal-directed or habitual. In this thesis, the possible causal role of specific brain regions in controlling this balance between goal-directed and habitual behaviour, as measured in the contingency degradation paradigm, were determined. As argued in the thesis Introduction, studies of the marmoset help to bridge rodent and human studies, including possible clinical translation, one of the reasons being the homologies that exist for the prefrontal cortex (PFC). A novel touchscreen-based contingency degradation task was developed for the common marmoset monkey, a New World non-human primate. The possible roles of the primate medial PFC (area 32), anterior cingulate cortex (area 24), ventromedial PFC (area 14-25), anterior orbitofrontal cortex (OFC, area 11), medial OFC (area 14) and the caudate nucleus (CN) were then compared following training, using reversible pharmacological inactivation and activation of these structures via implanted cannulae. None of the studies in the literature had examined the causal role of these brain regions in the expression of A-O associations as measured by contingency degradation. Inactivation of either area 24 or the CN significantly impaired the animals’ sensitivity to contingency degradation, as did activation of area 24. These findings suggest that area 24 and the CN may form part of a neural circuit that mediates the expression of A-O contingencies, a hypothesis supported by an anatomical tracing study. By contrast, inactivation of area 11 apparently enhanced sensitivity to instrumental contingency degradation, possibly by blocking competing pavlovian associations. Manipulations of area 14, 25 or area 32 did not affect sensitivity, indicating the neuroanatomical specificity of the contingency degradation deficits. Control experiments ruled out the possible contribution of effects on primary motivation or any non-specific effects of inactivation or activation. The findings are interpreted in the light of literature suggesting that the PFC sub-regions have largely distinctive but overlapping roles in controlling goal-directed behaviour. Additionally, a specific PFC sub-region, area 24, may work together with anterior CN to maintain and utilise learned causal relationships between actions and outcomes. The current thesis’s study on the expression of goal-directed knowledge may be useful for explaining the chronic psychopathology of several psychiatric disorders, including obsessive-compulsive disorder, as well as its possible neural substrates

Action-sequence learning, habits and automaticity in obsessive-compulsive disorder

Enhanced habit formation, greater automaticity and impaired goal/habit arbitration in obsessive-compulsive disorder (OCD) are key hypotheses from the goal/habit imbalance theory of compulsion which have not been directly investigated. This article tests these hypotheses using a combination of newly developed behavioral tasks. First, we trained patients with OCD and healthy controls, using a novel smartphone app, to perform chunked action sequences, previously shown to engage habit brain circuitry. The motor training was daily over one month period. There was equivalent procedural learning and attainment of habitual performance (measured with an objective criteria of automaticity) in both groups, despite greater subjective habitual tendencies in patients with OCD, self-reported via a recently developed questionnaire. We then used a combination of follow-up behavioral tasks to further assess the arbitration between previous automatic and new goal-directed action sequences. We found no evidence for impairments of goal/habit arbitration in OCD following re-evaluation based on monetary feedback, although there was a greater preference for engaging in the trained habitual sequence under certain conditions which may have derived from its intrinsic value. These findings may lead to a reformulation of the goal/habit imbalance hypothesis in OCD. Finally, OCD patients with higher compulsivity scores and habitual tendencies showed more engagement with the motor habit-training app and reported symptom alleviation, with implications for its potential use as a form of habit reversal therapy