CiteULike: Tag basal_ganglia

The basal ganglia: learning new tricks and loving it.

AM Graybiel — 2006-02-06T19:49:44-00:00

Curr Opin Neurobiol, Vol. 15, No. 6. (December 2005), pp. 638-644.

The field of basal ganglia research is exploding on every level - from discoveries at the molecular level to those based on human brain imaging. A remarkable series of new findings support the view that the basal ganglia are essential for some forms of learning-related plasticity. Other new findings are challenging some of the basic tenets of the field as it now stands. Combined with the new evidence on learning-related functions of the basal ganglia, these studies suggest that the basal ganglia are parts of a brain-wide set of adaptive neural systems promoting optimal motor and cognitive control.

Using TD learning to simulate working memory performance in a model of the prefrontal cortex and basal ganglia

Ahmed Moustafa — 2007-10-31T07:13:21-00:00

Cognitive Systems Research, Vol. 8, No. 4. (December 2007), pp. 262-281.

Delayed-response tasks (DRTs) have been used to assess working memory (WM) processes in human and nonhuman animals. Experiments have shown that the basal ganglia (BG) and dorsolateral prefrontal cortex (DLPFC) subserve DRT performance. Here, we report the results of simulation studies of a systems-level model of DRT performance. The model was trained using the temporal difference (TD) algorithm and uses an actor-critic architecture. The matrisomes of the BG represent the actor and the striosomes represent the critic. Unlike existing models, we hypothesize that the BG subserve the selection of both motor- and cognitive-related information in these tasks. We also assume that the learning of both processes is based on reward presentation. A novel feature of the model is the incorporation of delay-active neurons in the matrisomes, in addition to DLPFC. Another novel feature of the model is the subdivision of the matrisomal neurons into segregated winner-take-all (WTA) networks consisting of delay- versus transiently-active units. Our simulation model proposes a new neural mechanism to account for the occurrence of perseverative responses in WM tasks in striatal-, as well as in prefrontal damaged subjects. Simulation results also show that the model both accounts for the phenomenon of time shifting of dopamine phasic signals and the effects of partial reinforcement and reward magnitude on WM performance at both behavioral and neural levels. Our simulation results also found that the TD algorithm can subserve learning in delayed-reversal tasks.

Different brain circuits underlie motor and perceptual representations of temporal intervals

Domenica Bueti — 2008-04-18T09:15:12-00:00

J. Cognitive Neuroscience, Vol. 20, No. 2. (February 2008), pp. 204-214.

Role of the basal ganglia and frontal cortex in selecting and producing internally guided force pulses

David Vaillancourt — 2007-09-04T16:25:02-00:00

NeuroImage, Vol. 36, No. 3. (1 July 2007), pp. 793-803.

The basal ganglia comprise a crucial circuit involved in force production and force selection, but the specific role of each nucleus to the production of force pulses and the selection of pulses of different force amplitudes remains unknown. We conducted an fMRI study in which participants produced force using a precision grip while (a) holding a steady-state force, (b) performing a series of force pulses with similar amplitude, and (c) selecting force pulses of different amplitude. Region of interest analyses were conducted in the basal ganglia and frontal cortex to compare percent signal change during force pulse versus steady-state force production and compare force amplitude selection to force production when selection of force amplitude was not present. There were three novel findings in the basal ganglia. First, the caudate nucleus increased activation during the selection of different force amplitudes when compared to producing a series of similar force pulses. Second, GPi, STN, and posterior putamen increased activation during the production of similar force amplitudes when compared to holding a steady-state force, and maintained similar activation during the production of different force amplitudes in which force selection was required. Third, GPe and anterior putamen had increased activation during the production of similar force pulses and further increased activation during the selection of different force pulses. These findings suggest that anterior basal ganglia nuclei are involved in selecting the amplitude of force contractions and posterior basal ganglia nuclei regulate basic aspects of dynamic force pulse production.

Hold your horses: A dynamic computational role for the subthalamic nucleus in decision making.

Michael Frank — 2006-09-28T18:04:56-00:00

Neural Networks (29 August 2006)

The basal ganglia (BG) coordinate decision making processes by facilitating adaptive frontal motor commands while suppressing others. In previous work, neural network simulations accounted for response selection deficits associated with BG dopamine depletion in Parkinson's disease. Novel predictions from this model have been subsequently confirmed in Parkinson patients and in healthy participants under pharmacological challenge. Nevertheless, one clear limitation of that model is in its omission of the subthalamic nucleus (STN), a key BG structure that participates in both motor and cognitive processes. The present model incorporates the STN and shows that by modulating when a response is executed, the STN reduces premature responding and therefore has substantial effects on which response is ultimately selected, particularly when there are multiple competing responses. Increased cortical response conflict leads to dynamic adjustments in response thresholds via cortico-subthalamic-pallidal pathways. The model accurately captures the dynamics of activity in various BG areas during response selection. Simulated dopamine depletion results in emergent oscillatory activity in BG structures, which has been linked with Parkinson's tremor. Finally, the model accounts for the beneficial effects of STN lesions on these oscillations, but suggests that this benefit may come at the expense of impaired decision making.

Cortico–basal ganglia circuit mechanism for a decision threshold in reaction time tasks

Chung-Chuan Lo — 2006-06-28T17:36:05-00:00

Nature Neuroscience, Vol. 9, No. 7. (11 June 2006), pp. 956-963.

The basal ganglia in human learning.

CA Seger — 2006-08-16T21:58:22-00:00

Neuroscientist, Vol. 12, No. 4. (August 2006), pp. 285-290.

For many years, the basal ganglia were described in anatomy courses as strictly motor structures. Certainly, some of the most obvious and debilitating symptoms shown by persons with basal ganglia disorders are problems in motor control. However, the basal ganglia are not limited to motoric aspects of behavior: recent research shows that they are involved in most areas of cognitive and emotional functioning, consistent with their anatomical connections with all areas of the cortex. This review will focus on the roles of the basal ganglia in human learning, particularly sequence learning and category learning. Current areas of research that are discussed include the differing roles of different basal ganglia regions, patterns of interaction between the cortex and basal ganglia, differences in positive and negative association learning, effects of dopaminergic medication on learning, whether basal ganglia-mediated learning is implicit or explicit, and how the basal ganglia learning systems interact with other learning systems, particularly within the medial temporal lobe.

Dopamine modulation in the basal ganglia locks the gate to working memory.

AJ Gruber — 2006-11-21T13:36:48-00:00

J Comput Neurosci, Vol. 20, No. 2. (April 2006), pp. 153-166.

The prefrontal cortex and basal ganglia are deeply implicated in working memory. Both structures are subject to dopaminergic neuromodulation in a way that exerts a critical influence on the proper operation of working memory. We present a novel network model to elucidate the role of phasic dopamine in the interaction of these two structures in initiating and maintaining mnemonic activity. We argue that neuromodulation plays a critical role in protecting memories against both internal and external sources of noise. Increases in cortical gain engendered by prefrontal dopamine release help make memories robust against external distraction, but do not offer protection against internal noise accompanying recurrent cortical activity. Rather, the output of the basal ganglia provides the gating function of stabilization against noise and distraction by enhancing select memories through targeted disinhibition of cortex. Dopamine in the basal ganglia effectively locks this gate by influencing the stability of up and down states in the striatum. Dopamine's involvement in affective processing endows this gating with specificity to motivational salience. We model a spatial working memory task and show that these combined effects of dopamine lead to superior performance.

Reward prediction in primate basal ganglia and frontal cortex

Wolfram Schultz — 2007-07-23T18:32:24-00:00

Neuropharmacology, Vol. 37, No. 4-5. (5 April 1998), pp. 421-429.

Reward information is processed in a limited number of brain structures, including fronto-basal ganglia systems. Dopamine neurons respond phasically to primary rewards and reward-predicting stimuli depending on reward unpredictability but without discriminating between rewards. These responses reflect `errors' in the prediction of rewards in correspondence to learning theories and thus may constitute teaching signals for appetitive learning. Neurons in the striatum (caudate, putamen, ventral striatum) code reward predictions in a different manner. They are activated during several seconds when animals expect predicted rewards. During learning, these activations occur initially in rewarded and unrewarded trials and become subsequently restricted to rewarded trials. This occurs in parallel with the adaptation of reward expectations by the animals, as inferred from their behavioral reactions. Neurons in orbitofrontal cortex respond differentially to stimuli predicting different liquid rewards, without coding spatial or visual features. Thus, different structures process reward information processed in different ways. Whereas dopamine neurons emit a reward teaching signal without indicating the specific reward, striatal neurons adapt expectation activity to new reward situations, and orbitofrontal neurons process the specific nature of rewards. These reward signals need to cooperate in order for reward information to be used for learning and maintaining approach behavior.

How do memory systems interact? Evidence from human classification learning.

RA Poldrack — 2007-06-01T15:50:28-00:00

Neurobiol Learn Mem, Vol. 82, No. 3. (November 2004), pp. 324-332.

Studies of human classification learning using functional neuroimaging have suggested that basal ganglia and medial temporal lobe memory systems may interact during learning. We review these results and outline a set of possible mechanisms for such interactions. Effective connectivity analyses suggest that interaction between basal ganglia and medial temporal lobe are mediated by prefrontal cortex rather than by direct connectivity between regions. A review of possible neurobiological mechanisms suggests that interactions may be driven by neuromodulatory systems in addition to mediation by interaction of inputs to prefrontal cortical neurons. These results suggest that memory system interactions may reflect multiple mechanisms that combine to optimize behavior based on experience.

Opposing basal ganglia processes shape midbrain visuomotor activity bilaterally

Huai Jiang — 2006-12-06T12:39:03-00:00

Nature, Vol. 423, No. 6943. (26 June 2003), pp. 982-986.

Responses to reward in monkey dorsal and ventral striatum.

P Apicella — 2006-01-25T22:59:31-00:00

Exp Brain Res, Vol. 85, No. 3. (1991), pp. 491-500.

The sources of input and the behavioral effects of lesions and drug administration suggest that the striatum participates in motivational processes. We investigated the activity of single striatal neurons of monkeys in response to reward delivered for performing in a go-nogo task. A drop of liquid was given each time the animal correctly executed or withheld an arm movement in reaction to a visual stimulus. Of 1593 neurons, 115 showed increased activity in response to delivery of liquid reward in both go and nogo trials. Responding neurons were predominantly located in dorsal and ventromedial parts of anterior putamen, in dorsal and ventral caudate, and in nucleus accumbens. They were twice as frequent in ventral as compared to dorsal striatal areas. Responses occurred at a median latency of 337 ms and lasted for 525 ms, with insignificant differences between dorsal and ventral striatum. Reward responses differed from activity recorded in the face area of posterior putamen which varied synchronously with individual mouth movements. Responses were directly related to delivery of primary liquid reward and not to auditory stimuli associated with it. Most of them also occurred when reward was delivered outside of the task. These results demonstrate that neurons of dorsal and particularly ventral striatum are involved in processing information concerning the attribution of primary reward.

Parallel organization of functionally segregated circuits linking basal ganglia and cortex.

GE Alexander — 2007-04-11T21:42:20-00:00

Annu Rev Neurosci, Vol. 9 (1986), pp. 357-381.

Neuronal activity in the basal ganglia and thalamus in patients with dystonia.

P Zhuang — 2007-08-14T18:14:26-00:00

Clin Neurophysiol, Vol. 115, No. 11. (November 2004), pp. 2542-2557.

OBJECTIVE: To explore the role of abnormal neuronal activity in the basal ganglia and thalamus in the generation of dystonia. METHODS: Microelectrode recording was performed in the globus pallidus internus (GPi), ventral thalamic nuclear group ventral oral posterior/ventral intermediate, Vop/Vim) and subthalamic nucleus (STN) in patients with primary dystonia (n=11) or secondary dystonia (n=9) during surgery. Electromyogram (EMG) was simultaneously recorded in selected muscle groups. Single unit analysis and cross-correlations were carried out. RESULTS: Three hundred and sixty-seven neurons were obtained from 29 trajectories (GPi: 13; Vop/Vim: 12; STN: 4), 87% exhibited altered neuronal activity including grouped discharges in GPi (n=79) and STN (n=37), long-lasting neuronal activity (n=70) and rapid neuronal discharge (n=86) in Vop/Vim. There were neurons in Vop, GPi and STN firing at the same frequency as EMG during dystonia (mean: 0.39 Hz, range 0.12-0.84 Hz). Significant correlations between neuronal activity and EMG at the frequency of dystonia were obtained (GPi: r2=0.7 (n=31), Vop/Vim: r2=0.64 (n=18) and STN: r2=0.86 (n=17)). CONCLUSIONS: Consistent with previous findings of abnormalities observed in Vop/VIM and GPi in relation to dystonia, the present data further show that the altered activity in GPi, specifically in dorsal subregions of GPi, Vop/Vim and STN is likely to be directly involved in the production of dystonic movement. Dystonia-related neuronal activity observed in motor thalamus and basal ganglia nuclei of GPi and STN indicates a critical role of their interactions affecting both indirect and direct pathways in the development of either generalized or focal dystonia. SIGNIFICANCE: These data support a central role of the basal ganglia in producing dystonic movements.

The basal ganglia: Focused selection and inhibition of competing motor programs

JW Mink — 2007-08-03T15:34:17-00:00

Progress in Neurobiology, Vol. 50 (November 1996), pp. 381-425.

The basal ganglia comprise several nuclei in the forebrain, diencephalon, and midbrain thought to play a significant role in the control of posture and movement. It is well recognized that people with degenerative diseases of the basal ganglia suffer from rigidly held abnormal body postures, slowing of movement, involuntary movements, or a combination of these abnormalities. However, it has not been agreed just what the basal ganglia contribute to normal movement. Recent advances in knowledge of the basal ganglia circuitry, activity of basal ganglia neurons during movement, and the effect of basal ganglia lesions have led to a new hypothesis of basal ganglia function. The hypothesis states that the basal ganglia do not generate movements. Instead, when voluntary movement is generated by cerebral cortical and cerebellar mechanisms, the basal ganglia act broadly to inhibit competing motor mechanisms that would otherwise interfere with the desired movement. Simultaneously, inhibition is removed focally from the desired motor mechanisms to allow that movement to proceed. Inability to inhibit competing motor programs results in slow movements, abnormal postures and involuntary muscle activity. Copyright (C) 1996 Elsevier Science Ltd.

Differential Effects of 6-OHDA Lesions of the Frontal Cortex and Caudate Nucleus on the Ability to Acquire an Attentional Set

HS Crofts — 2008-05-20T00:38:32-00:00

Cereb. Cortex, Vol. 11, No. 11. (1 November 2001), pp. 1015-1026.

Evidence from both human and animal studies indicates that catecholamine (dopamine and noradrenaline) imbalances in the fronto-striatal circuitry are associated with deficits in higher- order cognitive functions. The present study examined how cat- echolamines within this circuitry modulate attentional function, specifically the ability to develop, maintain, and shift an attentional set. Catecholamine depletions within the frontal cortex of the common marmoset impaired the ability to acquire an attentional set, and increased susceptibility to distraction from task-irrelevant stimuli. Analysis of set-shifting performance with stimulus dimen- sions of varying salience suggested that frontal catecholamine depletion selectively disrupts top-down', but not bottom-up' attentional processing. In contrast, the ability to acquire and shift an attentional set remained intact following dopaminergic depletion from the caudate nucleus. However, the reduced susceptibility to distraction from task-irrelevant stimuli displayed by monkeys with dopaminergic depletions of the caudate nucleus suggests that responding was under more rigid control by the currently rewarded stimulus. The results demonstrate opposite behavioural effects of 6-hydroxydopamine (6-OHDA) lesions in the frontal cortex and caudate nucleus in tasks requiring selective attention. Frontal catecholamine depletion caused an increase in distractibility while caudate dopamine loss induced greater focusing of responding. 10.1093/cercor/11.11.1015

A three-dimensional, histological and deformable atlas of the human basal ganglia. I. Atlas construction based on immunohistochemical and MRI data

Jerome Yelnik — 2007-10-05T22:47:42-00:00

NeuroImage, Vol. 34, No. 2. (15 January 2007), pp. 618-638.

This paper describes the construction of an atlas of the human basal ganglia. The successive steps of the construction were as follows. First a postmortem specimen was subjected to a MRI acquisition prior to extraction of the brain from the skull. The brain was then cryosectioned (70 [mu]m thickness). One section out of ten (80 sections) was Nissl-stained with cresyl violet, another series of 80 sections was immunostained for the calcium binding protein calbindin. Contours of basal ganglia nuclei including their calbindin-stained functional subdivisions, fiber bundles and ventricles (n = 80 structures) were traced from histological sections and digitized. A novelty of this atlas is the MRI acquisition, which represents the core data element of the study. MRI was used for the coregistration of the atlas data and permitted, through multimodal (Nissl, calbindin, images of cryosectioning, T1 and T2 MRI) and 3D optimization, the production of anatomically and geometrically consistent 3D surfaces, which can be sliced through any desired orientation. The atlas MRI is also used for its deformation to provide accurate conformation to the MRI of living patients, thus adding information at the histological level to the patient's MRI volume. This latter aspect will be presented in a forthcoming paper.

Cortical connectivity after subcortical stroke assessed with functional magnetic resonance imaging

Christian Grefkes — 2008-03-13T01:03:33-00:00

Annals of Neurology, Vol. 63, No. 2. (2008), pp. 236-246.

Methylphenidate Has Differential Effects on Blood Oxygenation Level-Dependent Signal Related to Cognitive Subprocesses of Reversal Learning

Chris Dodds — 2008-06-05T12:27:57-00:00

J. Neurosci., Vol. 28, No. 23. (4 June 2008), pp. 5976-5982.

Complete understanding of the neural mechanisms by which stimulants such as methylphenidate ameliorate attention deficit hyperactivity disorder is lacking. Theories of catecholamine function predict that the neural effects of stimulant drugs will vary according to task requirements. We used event-related, pharmacological functional magnetic resonance imaging to investigate the effects of 60 mg of methylphenidate, alone and in combination with 400 mg of sulpiride, on blood oxygenation level-dependent (BOLD) signal in a group of 20 healthy participants during probabilistic reversal learning, in a placebo-controlled design. In a whole-brain analysis, methylphenidate attenuated BOLD signal in the ventral striatum during response switching after negative feedback but modulated activity in the prefrontal cortex when subjects maintained their current response set. The results show that the precise neural site of modulation by methylphenidate depends on the nature of the cognitive subprocess recruited. 10.1523/JNEUROSCI.1153-08.2008

Distinct basal ganglia territories are engaged in early and advanced motor sequence learning.

S Lehéricy — 2006-01-24T19:06:32-00:00

Proc Natl Acad Sci U S A, Vol. 102, No. 35. (30 August 2005), pp. 12566-12571.

In this study, we used functional MRI (fMRI) at high field (3T) to track the time course of activation in the entire basal ganglia circuitry, as well as other motor-related structures, during the explicit learning of a sequence of finger movements over a month of training. Fourteen right-handed healthy volunteers had to practice 15 min daily a sequence of eight moves using the left hand. MRI sessions were performed on days 1, 14 and 28. In both putamen, activation decreased with practice in rostrodorsal (associative) regions. In contrast, there was a significant signal increase in more caudoventral (sensorimotor) regions of the putamen. Subsequent correlation analyses between signal variations and behavioral variables showed that the error rate (movement accuracy) was positively correlated with signal changes in areas activated during early learning, whereas reaction time (movement speed) was negatively correlated with signal changes in areas activated during advanced learning stages, including the sensorimotor putamen and globus pallidus. These results suggest the possibility that motor representations shift from the associative to the sensorimotor territories of the striato-pallidal complex during the explicit learning of motor sequences, suggesting that motor skills are stored in the sensorimotor territory of the basal ganglia that supports a speedy performance.

Habits, Rituals, and the Evaluative Brain

Ann Graybiel — 2008-07-17T00:19:01-00:00

Annual Review of Neuroscience, Vol. 31, No. 1. (2008), pp. 359-387.

Scientists in many different fields have been attracted to the study of habits because of the power habits have over behavior and because they invoke a dichotomy between the conscious, voluntary control over behavior, considered the essence of higher-order deliberative behavioral control, and lower-order behavioral control that is scarcely available to consciousness. A broad spectrum of behavioral routines and rituals can become habitual and stereotyped through learning. Others have a strong innate basis. Repetitive behaviors can also appear as cardinal symptoms in a broad range of neurological and neuropsychiatric illness and in addictive states. This review suggests that many of these behaviors could emerge as a result of experience-dependent plasticity in basal ganglia-based circuits that can influence not only overt behaviors but also cognitive activity. Culturally based rituals may reflect privileged interactions between the basal ganglia and cortically based circuits that influence social, emotional, and action functions of the brain.

Role for Subthalamic Nucleus Neurons in Switching from Automatic to Controlled Eye Movement

Masaki Isoda — 2008-07-10T01:23:17-00:00

J. Neurosci., Vol. 28, No. 28. (9 July 2008), pp. 7209-7218.

The subthalamic nucleus (STN) of the basal ganglia is an important element of motor control. This is demonstrated by involuntary movements induced by STN lesions and the successful treatment of Parkinson's disease by STN stimulation. However, it is still unclear how individual STN neurons participate in motor control. Here, we report that the STN has a function in switching from automatic to volitionally controlled eye movement. In the STN of trained macaque monkeys, we found neurons that showed a phasic change in activity specifically before volitionally controlled saccades which were switched from automatic saccades. A majority of switch-related neurons were considered to inhibit no-longer-valid automatic processes, and the inhibition started early enough to enable the animal to switch. We suggest that the STN mediates the control signal originated from the medial frontal cortex and implements the behavioral switching function using its connections with other basal ganglia nuclei and the superior colliculus. 10.1523/JNEUROSCI.0487-08.2008

Understanding the Neural Computations of Arbitrary Visuomotor Learning through fMRI and Associative Learning Theory.

Andrea Brovelli — 2007-11-25T04:51:36-00:00

Cereb Cortex (21 November 2007)

Associative theory postulates that learning the consequences of our actions in a given context is represented in the brain as stimulus-response-outcome associations that evolve according to prediction-error signals (the discrepancy between the observed and predicted outcome). We tested the theory on brain functional magnetic resonance imaging data acquired from human participants learning arbitrary visuomotor associations. We developed a novel task that systematically manipulated learning and induced highly reproducible performances. This granted the validation of the model-based results and an in-depth analysis of the brain signals in representative single trials. Consistent with the Rescorla-Wagner model, prediction-error signals are computed in the human brain and selectively engage the ventral striatum. In addition, we found evidence of computations not formally predicted by the Rescorla-Wagner model. The dorsal fronto-parietal network, the dorsal striatum, and the ventrolateral prefrontal cortex are activated both on the incorrect and first correct trials and may reflect the processing of relevant visuomotor mappings during the early phases of learning. The left dorsolateral prefrontal cortex is selectively activated on the first correct outcome. The results provide quantitative evidence of the neural computations mediating arbitrary visuomotor learning and suggest new directions for future computational models.

Evidence for Segregated and Integrative Connectivity Patterns in the Human Basal Ganglia

Bogdan Draganski — 2008-07-10T00:53:42-00:00

J. Neurosci., Vol. 28, No. 28. (9 July 2008), pp. 7143-7152.

Detailed knowledge of the anatomy and connectivity pattern of cortico-basal ganglia circuits is essential to an understanding of abnormal cortical function and pathophysiology associated with a wide range of neurological and neuropsychiatric diseases. We aim to study the spatial extent and topography of human basal ganglia connectivity in vivo. Additionally, we explore at an anatomical level the hypothesis of coexistent segregated and integrative cortico-basal ganglia loops. We use probabilistic tractography on magnetic resonance diffusion weighted imaging data to segment basal ganglia and thalamus in 30 healthy subjects based on their cortical and subcortical projections. We introduce a novel method to define voxel-based connectivity profiles that allow representation of projections from a source to more than one target region. Using this method, we localize specific relay nuclei within predefined functional circuits. We find strong correlation between tractography-based basal ganglia parcellation and anatomical data from previously reported invasive tracing studies in nonhuman primates. Additionally, we show in vivo the anatomical basis of segregated loops and the extent of their overlap in prefrontal, premotor, and motor networks. Our findings in healthy humans support the notion that probabilistic diffusion tractography can be used to parcellate subcortical gray matter structures on the basis of their connectivity patterns. The coexistence of clearly segregated and also overlapping connections from cortical sites to basal ganglia subregions is a neuroanatomical correlate of both parallel and integrative networks within them. We believe that this method can be used to examine pathophysiological concepts in a number of basal ganglia-related disorders. 10.1523/JNEUROSCI.1486-08.2008

Role of Dopamine in the Primate Caudate Nucleus in Reward Modulation of Saccades

Kae Nakamura — 2006-05-18T13:44:16-00:00

J. Neurosci., Vol. 26, No. 20. (17 May 2006), pp. 5360-5369.

Expected reward impacts behavior and neuronal activity in brain areas involved in sensorimotor processes. However, where and how reward signals affect sensorimotor signals is unclear. Here, we show evidence that reward-dependent modulation of behavior depends on normal dopamine transmission in the striatum. Monkeys performed a visually guided saccade task in which expected reward gain was different depending on the position of the target. Saccadic reaction times were reliably shorter on large-reward trials than on small-reward trials. When position-reward contingency was switched, the reaction time difference changed rapidly. Injecting dopamine D1 antagonist into the caudate significantly attenuated the reward-dependent saccadic reaction time changes. Conversely, injecting D2 antagonist into the same region enhanced the reward-dependent changes. These results suggest that reward-dependent changes in saccadic eye movements depend partly on dopaminergic modulation of neuronal activity in the caudate nucleus. 10.1523/JNEUROSCI.4853-05.2006

Basal Ganglia orient eyes to reward.

O Hikosaka — 2006-01-26T18:34:25-00:00

J Neurophysiol, Vol. 95, No. 2. (February 2006), pp. 567-584.

Expectation of reward motivates our behaviors and influences our decisions. Indeed, neuronal activity in many brain areas is modulated by expected reward. However, it is still unclear where and how the reward-dependent modulation of neuronal activity occurs and how the reward-modulated signal is transformed into motor outputs. Recent studies suggest an important role of the basal ganglia. Sensorimotor/cognitive activities of neurons in the basal ganglia are strongly modulated by expected reward. Through their abundant outputs to the brain stem motor areas and the thalamocortical circuits, the basal ganglia appear capable of producing body movements based on expected reward. A good behavioral measure to test this hypothesis is saccadic eye movement because its brain stem mechanism has been extensively studied. Studies from our laboratory suggest that the basal ganglia play a key role in guiding the gaze to the location where reward is available. Neurons in the caudate nucleus and the substantia nigra pars reticulata are extremely sensitive to the positional difference in expected reward, which leads to a bias in excitability between the superior colliculi such that the saccade to the to-be-rewarded position occurs more quickly. It is suggested that the reward modulation occurs in the caudate where cortical inputs carrying spatial signals and dopaminergic inputs carrying reward-related signals are integrated. These data support a specific form of reinforcement learning theories, but also suggest further refinement of the theory.

Expectation of reward modulates cognitive signals in the basal ganglia.

R Kawagoe — 2007-01-29T21:56:50-00:00

Nat Neurosci, Vol. 1, No. 5. (September 1998), pp. 411-416.

Action is controlled by both motivation and cognition. The basal ganglia may be the site where these kinds of information meet. Using a memory-guided saccade task with an asymmetric reward schedule, we show that visual and memory responses of caudate neurons are modulated by expectation of reward so profoundly that a neuron's preferred direction often changed with the change in the rewarded direction. The subsequent saccade to the target was earlier and faster for the rewarded direction. Our results indicate that the caudate contributes to the determination of oculomotor outputs by connecting motivational values (for example, expectation of reward) to visual information.

Cortical substrates for exploratory decisions in humans

Nathaniel Daw — 2006-06-20T11:57:29-00:00

Nature, Vol. 441, No. 7095. (2006), pp. 876-879.

Representation of action-specific reward values in the striatum.

K Samejima — 2005-11-30T17:36:20-00:00

Science, Vol. 310, No. 5752. (25 November 2005), pp. 1337-1340.

The estimation of the reward an action will yield is critical in decision-making. To elucidate the role of the basal ganglia in this process, we recorded striatal neurons of monkeys who chose between left and right handle turns, based on the estimated reward probabilities of the actions. During a delay period before the choices, the activity of more than one-third of striatal projection neurons was selective to the values of one of the two actions. Fewer neurons were tuned to relative values or action choice. These results suggest representation of action values in the striatum, which can guide action selection in the basal ganglia circuit.

A Physiologically Plausible Model of Action Selection and Oscillatory Activity in the Basal Ganglia

Mark Humphries — 2006-12-19T10:08:45-00:00

J. Neurosci., Vol. 26, No. 50. (13 December 2006), pp. 12921-12942.

The basal ganglia (BG) have long been implicated in both motor function and dysfunction. It has been proposed that the BG form a centralized action selection circuit, resolving conflict between multiple neural systems competing for access to the final common motor pathway. We present a new spiking neuron model of the BG circuitry to test this proposal, incorporating all major features and many physiologically plausible details. We include the following: effects of dopamine in the subthalamic nucleus (STN) and globus pallidus (GP), transmission delays between neurons, and specific distributions of synaptic inputs over dendrites. All main parameters were derived from experimental studies. We find that the BG circuitry supports motor program selection and switching, which deteriorates under dopamine-depleted and dopamine-excessive conditions in a manner consistent with some pathologies associated with those dopamine states. We also validated the model against data describing oscillatory properties of BG. We find that the same model displayed detailed features of both gamma-band (30-80 Hz) and slow ([~]1 Hz) oscillatory phenomena reported by Brown et al. (2002) and Magill et al. (2001), respectively. Only the parameters required to mimic experimental conditions (e.g., anesthetic) or manipulations (e.g., lesions) were changed. From the results, we derive the following novel predictions about the STN-GP feedback loop: (1) the loop is functionally decoupled by tonic dopamine under normal conditions and recoupled by dopamine depletion; (2) the loop does not show pacemaking activity under normal conditions in vivo (but does after combined dopamine depletion and cortical lesion); (3) the loop has a resonant frequency in the gamma-band. 10.1523/JNEUROSCI.3486-06.2006

How laminar frontal cortex and basal ganglia circuits interact to control planned and reactive saccades

Joshua Brown — 2006-12-06T12:22:39-00:00

Neural Netw., Vol. 17, No. 4. (May 2004), pp. 471-510.

Effects of expectations for different reward magnitudes on neuronal activity in primate striatum.

HC Cromwell — 2005-04-08T21:40:19-00:00

J Neurophysiol, Vol. 89, No. 5. (May 2003), pp. 2823-2838.

In behavioral science, it is well known that humans and nonhuman animals are highly sensitive to differences in reward magnitude when choosing an outcome from a set of alternatives. We know that a realm of behavioral reactions is altered when animals begin to expect different levels of reward outcome. Our present aim was to investigate how the expectation for different magnitudes of reward influences behavior-related neurophysiology in the anterior striatum. In a spatial delayed response task, different instruction pictures are presented to the monkey. Each image represents a different magnitude of juice. By reaching to the spatial location where an instruction picture was presented, animals could receive the particular liquid amount designated by the stimulus. Reliable preferences in reward choice trials and differences in anticipatory licks, performance errors, and reaction times indicated that animals differentially expected the various reward amounts predicted by the instruction cues. A total of 374 of 2,000 neurons in the anterior parts of the caudate nucleus, putamen, and ventral striatum showed five forms of task-related activation during the preparation or execution of movement and activations preceding or following the liquid drop delivery. Approximately one-half of these striatal neurons showed differing response levels dependent on the magnitude of liquid to be received. Results of a linear regression analysis showed that reward magnitude and single cell discharge rate were related in a subset of neurons by a monotonic positive or negative relationship. Overall, these data support the idea that the striatum utilizes expectancies that contain precise information concerning the predicted, forthcoming level of reward in directing general behavioral reactions.

The basal ganglia and adaptive motor control.

AM Graybiel — 2006-01-06T11:56:58-00:00

Science, Vol. 265, No. 5180. (23 September 1994), pp. 1826-1831.

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

Input-output organization of the sensorimotor striatum in the squirrel monkey.

AW Flaherty — 2006-09-19T21:47:54-00:00

J Neurosci, Vol. 14, No. 2. (February 1994), pp. 599-610.

The basal ganglia receive massive inputs from the neocortex and send outputs that exert both inhibitory and disinhibitory control over parts of the frontal cortex and brainstem. Between these basal ganglia inputs and outputs lies the striatum, which receives most of the cortical afferents and projects to the basal ganglia output nuclei--the globus pallidus and substantia nigra. To analyze this system we conjointly labeled, in squirrel monkeys, sensorimotor cortical inputs to the striatum and striatal outputs to the globus pallidus. Anterograde tracers were injected into the motor (MI) and somatosensory (SI) cortical body maps, at sites determined by electrophysiological stimulation and recording. Retrograde tracers were stereotaxically injected into the external and internal pallidal segments (GPe and GPi). We found that multiple dispersed modules ("matrisomes") in the putamen that all received inputs from single body-part representations in sensorimotor cortex could, in turn, send convergent outputs to single sites in the pallidum. This divergence-reconvergence pattern was found for both GPe and GPi sites, and for inputs from both SI and MI cortex. Thus, information from a single functional region in the cortex can be split up at the striatal stage only to be brought back together in the pallidum. The temporary divergence may increase lateral interactions between sensorimotor matrisomes, as well as between matrisomes and striosomes. One function of striatal modularity may thus be to set up an associative network in the striatum, which might contribute to sensorimotor learning. We also found that some sets of matrisomes did not receive strong sensorimotor inputs, even though they projected to regions of GPe and GPi that are near the sensorimotor-recipient zones described above. Thus, the matrisomal system may sort MI/SI inputs and other inputs before transfer to paired regions of GPe and GPi.

Role of the basal ganglia in the control of purposive saccadic eye movements.

O Hikosaka — 2006-09-18T19:23:44-00:00

Physiol Rev, Vol. 80, No. 3. (July 2000), pp. 953-978.

In addition to their well-known role in skeletal movements, the basal ganglia control saccadic eye movements (saccades) by means of their connection to the superior colliculus (SC). The SC receives convergent inputs from cerebral cortical areas and the basal ganglia. To make a saccade to an object purposefully, appropriate signals must be selected out of the cortical inputs, in which the basal ganglia play a crucial role. This is done by the sustained inhibitory input from the substantia nigra pars reticulata (SNr) to the SC. This inhibition can be removed by another inhibition from the caudate nucleus (CD) to the SNr, which results in a disinhibition of the SC. The basal ganglia have another mechanism, involving the external segment of the globus pallidus and the subthalamic nucleus, with which the SNr-SC inhibition can further be enhanced. The sensorimotor signals carried by the basal ganglia neurons are strongly modulated depending on the behavioral context, which reflects working memory, expectation, and attention. Expectation of reward is a critical determinant in that the saccade that has been rewarded is facilitated subsequently. The interaction between cortical and dopaminergic inputs to CD neurons may underlie the behavioral adaptation toward purposeful saccades.

Electrophysiological localization of the substantia nigra in the parkinsonian nonhuman primate.

PA Starr — 2007-01-10T20:01:28-00:00

J Neurosurg, Vol. 93, No. 4. (October 2000), pp. 704-710.

During ablative surgery and implantation of deep-brain stimulators for the treatment of movement disorders, electrophysiological techniques are often used for localization of subcortical targets. New restorative therapies for Parkinson disease, aimed at delivering drugs or cells to the substantia nigra (SN), are becoming available. Therefore, precise surgical approaches to the dopaminergic cell-containing region of the SN are required to avoid damage to nearby structures such as the corticospinal tract and subthalamic nucleus. In a study conducted in nonhuman primates, the authors evaluated the utility and accuracy of electrophysiological techniques in localizing the SN. Three adult rhesus monkeys were used as hosts for intranigral cell transplants. The monkeys were rendered hemiparkinsonian by intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. With the aid of stereotactic guidance, chronic recording chambers were placed on the skull of each monkey and directed at the SN. In each monkey, 20 to 40 trajectories were explored with a microelectrode. Spontaneous and movement-related single-unit activities were recorded in the SN, pars reticulata, subthalamic nucleus, globus pallidus, striatum, thalamus, and red nucleus. Motor and ocular responses to microstimulation in the subthalamic area were noted. Using the electrophysiological and stereotactic information that was obtained, three-dimensional maps of the nigral complex were constructed to infer the location of the SN pars compacta. The maps were subsequently used to guide intranigral placement of fetal dopaminergic cells. Accurate delivery was verified by histological analysis. Based on the characteristic electrophysiological properties of the SN and surrounding structures in the parkinsonian state, microelectrode recording techniques may be used to ensure accurate placement of cell transplantation in the intranigral region.

Reward-predicting activity of dopamine and caudate neurons--a possible mechanism of motivational control of saccadic eye movement.

R Kawagoe — 2005-08-01T15:57:23-00:00

J Neurophysiol, Vol. 91, No. 2. (February 2004), pp. 1013-1024.

Recent studies have suggested that the basal ganglia are related to motivational control of behavior. To study how motivational signals modulate motor signals in the basal ganglia, we examined activity of midbrain dopamine (DA) neurons and caudate (CD) projection neurons while monkeys were performing a one-direction-rewarded version (1DR) of memory-guided saccade task. The cue stimulus indicated the goal position for an upcoming saccade and the presence or absence of reward after the trial. Among four monkeys we studied, three were sensitive to reward such that saccade velocity was significantly higher in the rewarded trials than in the nonrewarded trials; one monkey was insensitive to reward. In the reward-sensitive monkeys, both DA and CD neurons responded differentially to reward-indicating and no-reward-indicating cues. Thus DA neurons responded with excitation to a reward-indicating cue and with inhibition to a no-reward-indicating cue. A group of CD neurons responded to the cue in their response fields (mostly contralateral) and the cue response was usually enhanced when it indicated reward. In the reward-insensitive monkey, DA neurons showed no response to the cue, while the cue responses of CD neurons were not modulated by reward. Many CD neurons in the reward-sensitive monkeys, but not the reward-insensitive monkey, showed precue activity. These results suggest that DA neurons, with their connection to CD neurons, modulate the spatially selective signals in CD neurons in the reward-predicting manner and CD neurons in turn modulate saccade parameters with their polysynaptic connections to the oculomotor brain stem.

Activity of pallidal neurons during movement.

MR DeLong — 2006-01-27T20:33:45-00:00

J Neurophysiol, Vol. 34, No. 3. (May 1971), pp. 414-427.

The basal ganglia: focused selection and inhibition of competing motor programs.

JW Mink — 2006-09-18T14:36:24-00:00

Prog Neurobiol, Vol. 50, No. 4. (November 1996), pp. 381-425.

The basal ganglia comprise several nuclei in the forebrain, diencephalon, and midbrain thought to play a significant role in the control of posture and movement. It is well recognized that people with degenerative diseases of the basal ganglia suffer from rigidly held abnormal body postures, slowing of movement, involuntary movements, or a combination of these a abnormalities. However, it has not been agreed just what the basal ganglia contribute to normal movement. Recent advances in knowledge of the basal ganglia circuitry, activity of basal ganglia neurons during movement, and the effect of basal ganglia lesions have led to a new hypothesis of basal ganglia function. The hypothesis states that the basal ganglia do not generate movements. Instead, when voluntary movement is generated by cerebral cortical and cerebellar mechanisms, the basal ganglia act broadly to inhibit competing motor mechanisms that would otherwise interfere with the desired movement. Simultaneously, inhibition is removed focally from the desired motor mechanisms to allow that movement to proceed. Inability to inhibit competing motor programs results in slow movements, abnormal postures and involuntary muscle activity.

Functional properties of monkey caudate neurons. III. Activities related to expectation of target and reward.

O Hikosaka — 2006-09-14T16:36:00-00:00

J Neurophysiol, Vol. 61, No. 4. (April 1989), pp. 814-832.

1. The present paper reports complex neural activities in the monkey caudate nucleus that precede and anticipate visual stimuli and reward in learned visuomotor paradigms. These activities were revealed typically in the delayed saccade task in which memory and anticipation were required. We classified these activities according to their relationships to the task. 2. Activity related to expectation of a cue (n = 46) preceded the presentation of a spot of light (target cue) that signified the future location of saccade target. When the target cue was delayed, the activity was prolonged accordingly. The same spot of light was preceded by no activity if it acted as a distracting stimulus. 3. The sustained activity (n = 80) was a tonic discharge starting after the target cue as if holding the spatial information. 4. The activity related to expectation of target (n = 109) preceded the appearance of the target whose location was cued previously. It started with or after a saccade to the cued target location and ended with the appearance of the target. The activity was greater when the target was expected to appear in the contralateral visual field. 5. The activity related to expectation of reward (n = 57) preceded a task-specific reward. It started with the appearance of the final target and ended with the reward. In most cases, the activity was nonselective for how the monkey obtained the reward, i.e., by visual fixation only, by a saccade, or by a hand movement. The activity was dependent partly on visual fixation. 6. A few neurons showed tonic activity selectively before lever release and are thus considered to be related to the preparation of hand movements. 7. The activity related to breaking fixation (n = 33) occurred phasically if the monkey broke fixation, aborting the trial. 8. Activity related to reward (n = 104) was a phasic discharge that occurred before or after a reward of water was delivered. The activity was not simply related to a specific movement involved in the reward-obtaining behavior (eye, hand, or mouth movement). 9. Fixation-related activity (n = 72) was tonic activity continuing as long as the monkey attentively fixated a spot of light. It was dependent on reward expectancy in most cases. 10. The present results, together with those in the preceding papers, indicate that the activities of individual caudate neurons--sensory, motor, or cognitive--are dependent on specific contexts of learned behavior.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional properties of monkey caudate neurons. II. Visual and auditory responses.

O Hikosaka — 2006-09-14T16:35:33-00:00

J Neurophysiol, Vol. 61, No. 4. (April 1989), pp. 799-813.

1. Visual responses of caudate neurons were studied in monkeys trained to fixate on a small spot of light. A visual stimulus (another spot of light) was presented in various contexts of behavior using different behavioral paradigms. Visual receptive fields were usually large and centered on the contralateral hemifield. Among 217 neurons with visual responses, 184 were further classified into subtypes. 2. Visual responses in 64 neurons were not modulated by changing the paradigms (unconditional visual responses). In the other neurons, visual responses were dependent on the behavioral contexts in which the stimulus was presented. Three types of behavioral modulation were found. 3. A saccade-enhanced visual response (n = 37) was the one that was enhanced if the monkey made a saccade to the stimulus on its appearance. The enhancement was spatially selective: the response was depressed if the saccade was directed away from the stimulus. 4. Memory-contingent visual responses (n = 36) were present preferentially when the monkey remembered the location of the stimulus and a few seconds later made a saccade to the remembered location. Responses were greater when the location of the stimulus was randomized between trials. 5. Expectation-contingent visual responses (n = 46) were present preferentially when the stimulus came on while the monkey was not fixating another spot, and the stimulus was related directly to a reward. Unlike the other types, its receptive field included both contralateral and ipsilateral hemifields without a particular preference. 6. A small number of neurons (n = 16) showed a visual response that easily habituated. 7. Latencies of visual responses were usually between 100 and 200 ms. The latencies of the memory-contingent, expectation-contingent, and habituated visual responses tended to be longer than the others and tended to be more variable between trials. 8. Among auditory responsive neurons only a small proportion were related to the tasks. The response was greater to a contralateral sound. It was enhanced if the monkey used the sound as the cue for the future target location. 9. The results suggest that sensory responses of caudate neurons could be used to guide a subsequent sequence of learned behaviors by confirming predicted environmental states, renewing memory, or establishing a motor set.

Functional properties of monkey caudate neurons. I. Activities related to saccadic eye movements.

O Hikosaka — 2006-09-14T16:34:56-00:00

J Neurophysiol, Vol. 61, No. 4. (April 1989), pp. 780-798.

1. We recorded single cell activities in the caudate nucleus of the monkeys trained to perform a series of visuomotor tasks. In the first part of this paper, we summarize the types and locations of neurons in the monkey caudate nucleus. In the second part, we report the characteristics of neurons related to saccadic eye movements. 2. Neurons were classified into two types in terms of spontaneous discharge pattern. A majority of the neurons (2,287/2,559, 89%) had very low-frequency discharges (mostly less than 1 Hz). The rest (n = 272) showed irregular-tonic discharges (3-8 Hz) with broad spikes. 3. Of 2,559 neurons tested, 867 showed spike activity related to some aspects of the tasks; 502 neurons showed discharges in response to environmental changes outside, not in relation to, the tasks. None of the neurons responsive in or outside the tasks belonged to the irregular-tonic type. 4. The task-related activities were classified as: Saccade-related, Visual, Auditory, Cognitive, Fixation-related, and Reward-related. The activities detected outside the tasks were classified into: Visual, Auditory, Movement-related, Reward-related, and Other. Few neurons had both task-related and task-unrelated activities. 5. The locations of recorded neurons were determined using a coordinate system based on the anterior and posterior commissures. Task-related neurons were clustered longitudinally in the central part of the caudate. Neurons responsive outside the tasks were more widely distributed; specifically, auditory neurons were in the medial part, whereas movement-related neurons were in the lateral part. The irregular-tonic neurons were dispersed all over the caudate. 6. The monkey was trained to fixate on a spot of light on the screen and, when the spot moved, to follow it by making a saccade. A visually guided saccade occurred when the spot moved to another location without a time gap (saccade task). A memory-guided saccade occurred when the spot first disappeared and after a time gap reappeared at a fixed location (saccade with gap task). By delivering a cue stimulus while the monkey was fixating, a memory-guided saccade was elicited to a randomly chosen location (delayed saccade task).(ABSTRACT TRUNCATED AT 400 WORDS)

Role of primate substantia nigra pars reticulata in reward-oriented saccadic eye movement.

M Sato — 2006-09-18T14:26:16-00:00

J Neurosci, Vol. 22, No. 6. (15 March 2002), pp. 2363-2373.

To test the hypothesis that the basal ganglia are related to reward-oriented saccades, we examined activity of substantia nigra pars reticulata (SNr) neurons by using a one-direction-rewarded version of the memory-guided saccade task (1DR). Many SNr neurons changed (decreased or increased) their activity after and before a visual cue (post-cue and pre-cue activity). Post-cue decreases or increases tended to be larger to a contralateral cue. They were often modulated prospectively by the presence or absence of reward, either positively (enhanced in the rewarded condition) or negatively (enhanced in the nonrewarded condition). The positive reward modulation was more common among decreasing type neurons, whereas no such preference was observed among increasing type neurons. The reward-contingent decrease in SNr neuronal activity would facilitate rewarded saccades by inducing disinhibition in superior colliculus (SC) neurons. In contrast, the increase in SNr activity would suppress a saccade less selectively (rewarded or nonrewarded) by augmenting inhibition of SC neurons. The post-cue activity was often preceded by anticipatory pre-cue activity. Most typically, post-cue decrease was preceded by pre-cue decrease, selectively when the contralateral side was rewarded. This would reinforce the reward-oriented nature of SNr neuronal activity. The decreases and increases in SNr activity may be derived directly and indirectly, respectively, from the caudate (CD), where neurons show reward-contingent pre-cue and post-cue activity. These results suggest that the CD-SNr-SC mechanism would promote saccades oriented to reward.

The nucleus accumbens as part of a basal ganglia action selection circuit.

Saleem Nicola — 2006-09-25T18:19:07-00:00

Psychopharmacology (Berl) (16 September 2006)

BACKGROUND: The nucleus accumbens is the ventral extent of the striatum, the main input nucleus of the basal ganglia. Recent hypotheses propose that the accumbens and its dopamine projection from the midbrain contribute to appetitive behaviors required to obtain reward. However, the specific nature of this contribution is unclear. In contrast, significant advances have been made in understanding the role of the dorsal striatum in action selection and decision making. OBJECTIVE: In order to develop a hypothesis of the role of nucleus accumbens dopamine in action selection, the physiology and behavioral pharmacology of the nucleus accumbens are compared to those of the dorsal striatum. HYPOTHESES: Three hypotheses concerning the role of dopamine in these structures are proposed: (1) that dopamine release in the dorsal striatum serves to facilitate the ability to respond appropriately to temporally predictable stimuli (that is, stimuli that are so predictable that animals engage in anticipatory behavior just prior to the stimulus); (2) that dopamine in the nucleus accumbens facilitates the ability to respond to temporally unpredictable stimuli (which require interruption of ongoing behavior); and (3) that accumbens neurons participate in action selection in response to such stimuli by virtue of their direct (monosynaptic inhibitory) and indirect (polysynaptic excitatory) projections to basal ganglia output nuclei.

Contextual modulation of substantia nigra pars reticulata neurons.

A Handel — 2005-02-22T21:48:50-00:00

J Neurophysiol, Vol. 83, No. 5. (May 2000), pp. 3042-3048.

Neurons in the substantia nigra pars reticulata (SNr) are known to encode saccadic eye movements within some, but not all, behavioral contexts. However, the precise contextual factors that effect the modulations of nigral activity are still uncertain. To further examine the effect of behavioral context on the SNr, we recorded the activity of 72 neurons while monkeys made saccades during a delayed saccade task and during periods of free viewing. We quantified and compared the movement fields of each neuron for saccades made under three different conditions: 1) spontaneous saccades, which shifted gaze during periods of free viewing when no stimuli were presented and no reinforcements were delivered; 2) fixational saccades, which brought gaze into alignment with a fixation target at the start of a delayed saccade trial, were necessary for trial completion, but were not directly followed by reinforcement; and 3) terminal saccades, which brought gaze into alignment with a visual target at the end of a delayed saccade trial and were directly followed by reinforcement. For three of the four SNr neuron classes, saccade-related modulations were only present before terminal saccades. For the fourth class, discrete pausers, saccade-related modulations were substantially larger for terminal saccades than for fixational saccades, and modulations were absent for spontaneous saccades. These results and other recent work on the basal ganglia suggest that some saccade-related signals in the SNr may be influenced by the reinforcement associated with a particular saccadic eye movement.

Putting a spin on the dorsal-ventral divide of the striatum.

P Voorn — 2006-01-25T02:36:21-00:00

Trends Neurosci, Vol. 27, No. 8. (August 2004), pp. 468-474.

Since its conception three decades ago, the idea that the striatum consists of a dorsal sensorimotor part and a ventral portion processing limbic information has sparked a quest for functional correlates and anatomical characteristics of the striatal divisions. But this classic dorsal-ventral distinction might not offer the best view of striatal function. Anatomy and neurophysiology show that the two striatal areas have the same basic structure and that sharp boundaries are absent. Behaviorally, a distinction between dorsolateral and ventromedial seems most valid, in accordance with a mediolateral functional zonation imposed on the striatum by its excitatory cortical, thalamic and amygdaloid inputs. Therefore, this review presents a synthesis between the dorsal-ventral distinction and the more mediolateral-oriented functional striatal gradient.

Activity of Tonically Active Neurons in the Monkey Putamen During Initiation and Withholding of Movement

Irwin Lee — 2006-03-22T13:27:20-00:00

J Neurophysiol, Vol. 95, No. 4. (1 April 2006), pp. 2391-2403.

Tonically active neurons (TANs) of the primate striatum are putative interneurons that respond to events of motivational significance, such as primary rewards, and to sensory stimuli that predict such events. Because TANs influence striatal projection neurons, TANs may play a role in the initiation and control of movement. To examine this issue, we recorded from putaminal TANs in macaque monkeys trained to make the same arm movement in two ways--in reaction to an external cue and also after a variable delay without an explicit instruction to move (self-timed movements). On other trials, the animals had to withhold movement following an external cue. The task design ensured that the three types of trials were effectively randomly interleaved, equally frequent, and similar in overall timing. Separately, we presented "playback" trials in which the same sequence of visual stimulation and reward was presented while the animals fixated without making the arm movement. We found that TAN responses were strongly affected by behavioral context. In particular, TAN responses were strikingly stronger when the animals actively withheld movements than on the corresponding playback trials, even though the stimulus sequence and reward timing were identical and no movement was made in either case. Many TANs also became active in the absence of a proximate sensory cue on self-timed movements, suggesting that TANs may reflect internal processes that are specific to self-timed movements. These results suggest that TANs may directly participate in, or monitor the motivational significance of, an animal's actions as well as external events.

A neural correlate of response bias in monkey caudate nucleus.

J Lauwereyns — 2006-01-27T17:16:57-00:00

Nature, Vol. 418, No. 6896. (25 July 2002), pp. 413-417.

Primates are equipped with neural circuits in the prefrontal cortex, the parietal cortex and the basal ganglia that predict the availability of reward during the performance of behavioural tasks. It is not known, however, how reward value is incorporated in the control of action. Here we identify neurons in the monkey caudate nucleus that create a spatially selective response bias depending on the expected gain. In behavioural tasks, the monkey had to make a visually guided eye movement in every trial, but was rewarded for a correct response in only half of the trials. Reward availability was predictable on the basis of the spatial position of the visual target. We found that caudate neurons change their discharge rate systematically, even before the appearance of the visual target, and usually fire more when the contralateral position is associated with reward. Strong anticipatory activity of neurons with a contralateral preference is associated with decreased latency for eye movements in the contralateral direction. We conclude that this neuronal mechanism creates an advance bias that favours a spatial response when it is associated with a high reward value.

Dissociable roles of ventral and dorsal striatum in instrumental conditioning.

J O'Doherty — 2006-02-01T20:02:54-00:00

Science, Vol. 304, No. 5669. (16 April 2004), pp. 452-454.

Instrumental conditioning studies how animals and humans choose actions appropriate to the affective structure of an environment. According to recent reinforcement learning models, two distinct components are involved: a "critic," which learns to predict future reward, and an "actor," which maintains information about the rewarding outcomes of actions to enable better ones to be chosen more frequently. We scanned human participants with functional magnetic resonance imaging while they engaged in instrumental conditioning. Our results suggest partly dissociable contributions of the ventral and dorsal striatum, with the former corresponding to the critic and the latter corresponding to the actor.

Comparison of the basal ganglia and cerebellum in shifting attention.

SM Ravizza — 2007-01-29T22:24:45-00:00

J Cogn Neurosci, Vol. 13, No. 3. (1 April 2001), pp. 285-297.

The basal ganglia and cerebellum have traditionally been associated with motor performance. Recently, there has been considerable interest regarding the contributions of these subcortical structures to aspects of cognition. In particular, both the basal ganglia and cerebellum have been hypothesized to be involved in the control of attentional set. To date, no neuropsychological studies have directly compared the effects of basal ganglia and cerebellar dysfunction on the same attention shifting tasks. To this end, we employed an alternating attention task that has been used to demonstrate putative attentional control deficits in children with cerebellar pathology, either related to autism or neurological insult. When adult patients with either Parkinson's disease or cerebellar lesions were tested on this task, a similar pattern of deficits was observed for both groups. However, when the motor demands were reduced, cerebellar patients showed a significant improvement on the alternating attention task, whereas the Parkinson patients continued to exhibit an impairment. This dissociation suggests that attentional deficits reported previously as being due to cerebellar dysfunction may be, at least in part, secondary to problems related to coordinating successive responses. In contrast, attention-shifting deficits associated with basal ganglia impairment cannot be explained by recourse to the motor demands of the task.