Biomedical subjects

N Ramnani

Publications and source records attributed to N Ramnani.

10 recordsLinked to original sources

PubMed2004

Willed action and attention to the selection of action.

Actions are said to be 'willed' if we consciously pay attention to their selection. It has been suggested that they are associated with activations in the dorsal prefrontal cortex (area 46). However, because previous experiments typically used a 'free selection' paradigm to examine this hypothesis, it is unclear whether the results reflected the attention to the selection of action or the freedom of choice allowed by the tasks. In this experiment, we minimized the difference of working memory demand across task conditions by using novel stimuli in each trial. We found that activation in the dorsal prefrontal cortex on a free selection task was not significantly different from that induced by another task that required attention to the selection of action, although the responses were externally specified. This suggests that the dorsal prefrontal cortex is in fact associated with attention to the selection of action, but does not play a unique role in the generation of internally initiated actions. However, the presupplementary motor area (pre-SMA) may subserve this function as activity in this region was found to be tightly associated with the free selection of responses.

Adult↗

PubMed2004

Prediction error for free monetary reward in the human prefrontal cortex.

Making predictions about future rewards is an important ability for primates, and its neurophysiological mechanisms have been studied extensively. One important approach is to identify neural systems that process errors related to reward prediction (i.e., areas that register the occurrence of unpredicted rewards and the failure of expected rewards). In monkeys that have learned to predict appetitive rewards during reward-directed behaviors, dopamine neurons reliably signal both types of prediction error. The mechanisms in the human brain involved in processing prediction error for monetary rewards are not well understood. Furthermore, nothing is known of how such systems operate when rewards are not contingent on behavior. We used event-related fMRI to localize responses to both classes of prediction error. Subjects were able to predict a monetary reward or a nonreward on the basis of a prior visual cue. On occasional trials, cue-outcome contingencies were reversed (unpredicted rewards and failure of expected rewards). Subjects were not required to make decisions or actions. We compared each type of prediction error trial with its corresponding control trial in which the same prediction did not fail. Each type of prediction error evoked activity in a distinct frontotemporal circuit. Unexpected reward failure evoked activity in the temporal cortex and frontal pole (area 10). Unpredicted rewards evoked activity in the orbitofrontal cortex, the frontal pole, parahippocampal cortex, and cerebellum. Activity time-locked to prediction errors in frontotemporal circuits suggests that they are involved in encoding the associations between visual cues and monetary rewards in the human brain.

Basal Ganglia↗

PubMed2003

Instructed delay activity in the human prefrontal cortex is modulated by monetary reward expectation.

Goal-directed actions are executed with greater efficiency when the goals of the actions are rewarded and so the reward expectation must influence systems concerned with action-planning and motor control. However, little is known about how this influence is achieved in primates. Here, we demonstrate in human subjects that manual performance is enhanced when the goals of the visually cued actions are monetary rewards. We also used event-related fMRI in the same subjects to localize neural activity related to action preparation and selection that was influenced by the reward. We found three areas with significant interaction between reward and preparation: the prestriate visual cortex, the premotor cortex and the lateral prefrontal cortex. The latter two areas appear to be frontal systems integrating the expectation of rewards with selection and preparation of actions.

Analysis of Variance↗

PubMed2001

Changes in the human brain during rhythm learning.

Subjects were scanned with PET while they learned a complex arbitrary rhythm, paced by visual cues. In the comparison condition, the intervals were varied randomly. The behavioral results showed that the subjects decreased their response time with training, thus becoming more accurate in responding to the pacing cues at the appropriate time. There were learning-related increases in the posterior lateral cerebellum (lobule HVIIa), intraparietal and medial parietal cortex, presupplementary motor area (pre-SMA), and lateral premotor cortex. Learning-related decreases were found in the prestriate and inferior temporal cortex, suggesting that with practice the subjects increasingly came to depend on internal rather than external cues to time their responses. There were no learning-related increases in the basal ganglia. It is suggested that it is the neocortical-cerebellar loop that is involved in the timing and coordination of responses.

Adult↗

PubMed2001

Expanding cerebellar horizons.

Anatomical connections must underly neuronal function. A new study by Middleton and Strick shows that the cerebellum projects to the dorsal prefrontal cortex of the monkey. This could provide the basis for cerebellar modulation of cognitive processes.

Journal Article↗

PubMed2001

The cerebellum and parietal cortex play a specific role in coordination: a PET study.

The synthesis of complex, coordinated movements from simple actions is an important aspect of motor control. Lesion studies have revealed specific brain areas, particularly the cerebellum, to be essential for a variety of coordinated movements, and lend support to the view that the cerebellum is engaged in the integration of simple movements into compound ones. A PET study was therefore conducted to show which brain areas were active specifically during the coordinated execution of an arm and finger movement to visual targets. A two-by-two factorial design was employed, in which subjects either made arm or finger movements alone, made coordinated arm-finger movements, or made no movements. Voxels were identified where activity was significantly greater during the execution of coordinated movements than when movements were made alone and in which this increased activity could not be accounted for simply by the additive effects of the activations for each movement in isolation. The behavioral results showed that subjects coordinated arm and finger movements well during coordination scans. Coordination-specific activations were found in left anterior lobe and bilaterally in the paramedian lobules of the cerebellum. These are known to receive forelimb-specific spinocerebellar proprioceptive inputs that may be related to multijoint movements. The same areas also receive corticocerebellar afference from motor areas that may convey efference copy information to the cerebellum. Coordination-specific activations were also seen in areas of the posterior parietal cortex. The results provide direct evidence in healthy human subjects of specific cerebellar engagement during the coordination of movement, over and above the control of constituent movements.

Adult↗

PubMed2001

Learning arbitrary visuomotor associations: temporal dynamic of brain activity.

Primates can give behavioral responses on the basis of arbitrary, context-dependent rules. When sensory instructions and behavioral responses are associated by arbitrary rules, these rules need to be learned. This study investigates the temporal dynamics of functional segregation at the basis of visuomotor associative learning in humans, isolating specific learning-related changes in neurovascular activity across the whole brain. We have used fMRI to measure human brain activity during performance of two tasks requiring the association of visual patterns with motor responses. Both tasks were learned by trial and error, either before (visuomotor control) or during (visuomotor learning) the scanning session. Epochs of tasks performance ( approximately 30 s) were alternated with a baseline period over the whole scanning session ( approximately 50 min). We have assessed both linear and nonlinear modulations in the differential signal between tasks, independently from overall task differences. The performance indices of the visuomotor learning task smoothly converged onto the values of a steady-state control condition, according to nonlinear timecourses. Specific visuomotor learning-related activity has been found over a distributed cortical network, centred on a temporo-prefrontal circuit. These cortical time-modulated activities were supported early in learning by the hippocampal/parahippocampal complex, and late in learning by the basal ganglia system. These findings suggest the inferior temporal and the ventral prefrontal cortex are critical neural nodes for integrating perceptual information with executive processes.

Adult↗

PubMed2000

Learning- and expectation-related changes in the human brain during motor learning.

We have studied a simple form of motor learning in the human brain so as to isolate activity related to motor learning and the prediction of sensory events. Whole-brain, event-related functional magnetic resonance imaging (fMRI) was used to record activity during classical discriminative delay eyeblink conditioning. Auditory conditioned stimulus (CS+) trials were presented either with a corneal airpuff unconditioned stimulus (US, paired), or without a US (unpaired). Auditory CS- trials were never reinforced with a US. Trials were presented pseudorandomly, 66 times each. The subjects gradually produced conditioned responses to CS+ trials, while increasingly differentiating between CS+ and CS- trials. The increasing difference between hemodynamic responses for unpaired CS+ and for CS- trials evolved slowly during conditioning in the ipsilateral cerebellar cortex (Crus I/Lobule HVI), contralateral motor cortex and hippocampus. To localize changes that were related to sensory prediction, we compared trials on which the expected airpuff US failed to occur (Unpaired CS+) with trials on which it occurred as expected (Paired CS+). Error-related signals in the contralateral cerebellum and somatosensory cortex were seen to increase during learning as the sensory prediction became stronger. The changes seen in the ipsilateral cerebellar cortex may be due either to the violations of sensory predictions, or to learning-related increases in the excitability of cerebellar neurons to presentations of the CS+.

Acoustic Stimulation↗

PubMed1996

Reversible inactivations of the cerebellum prevent the extinction of conditioned nictitating membrane responses in rabbits.

1. Studies show that reversible inactivation of the anterior interpositus nucleus (AIP) of the cerebellum with muscimol (a GABAA agonist) prevents acquisition of the classically conditioned nictitating membrane response (NMR) in the rabbit. Here, we have used reversible inactivations of the AIP with muscimol to investigate the role of the cerebellum in the extinction of this response. 2. Experimental subjects were implanted with cannulae targeted to the AIP, through which muscimol could be infused via an injector cannula. This experiment was divided into three phases lasting 4 days, separated by 3 day intervals. Experimental and unoperated control subjects received acquisition training in phase 1; in phases 2 and 3 they received extinction training. 3. Presentation of the conditioned stimulus (CS) alone in phase 2 produced normal extinction in control subjects. Muscimol inactivation of the AIP in experimental subjects during phase 2 prevented extinction of conditioned responses (CRs), shown by initial high CR frequency in the first post-drug session of phase 3, which then extinguished in a manner indistinguishable from controls in phase 2. 4. Our findings support the suggestion that similar cerebellar circuitry is engaged in acquisition and extinction of NMR conditioning.

Animals↗

PubMed1996

Reversible inactivations of the cerebellum with muscimol prevent the acquisition and extinction of conditioned nictitating membrane responses in the rabbit.

Lesions of the cerebellum severely impair the classically conditioned nictitating membrane response (NMR) in rabbits. Thus, the cerebellum is essential for the production of conditioned responses (CRs), either because it is actively involved in NMR conditioning or because damage to it causes motor or other general deficits. To distinguish between these alternatives, the cerebellum may be inactivated during training. Inactivation of the cerebellum during acquisition training might result in the absence of CRs on initial trials of subsequent training without the neuronal blockade. The blockade may have prevented learning but it may have produced other deficits that require time or further training to overcome. This problem can be addressed by inactivating the cerebellum during extinction training. If inactivation during extinction training results in the immediate production of CRs when training is resumed without the blockade, then it may be concluded that extinction learning was prevented by the blockade-the presence of CRs argues against any deficits not associated with learning. We used muscimol to inactivate the cerebellum and test its involvement in acquisition and extinction of NMR conditioning in the same subjects. We injected muscimol close to the interpositus nucleus of the cerebellum 1 h before each of four daily training sessions of delay conditioning. Almost no CRs were produced in these training sessions-there was little or no acquisition of NMR conditioning during cerebellar inactivation. The subjects were then trained for four daily sessions without injections of muscimol. There were no CRs on initial trials of the first session of retraining, but all subjects produced CRs by the end of this session. The subjects then received four daily sessions of extinction training with muscimol inactivation of the nuclei-no CRs were produced. Extinction training then continued for four daily sessions without muscimol inactivation. On the first of these sessions, all subjects immediately produced high levels of CRs. These responses then extinguished within and between sessions with characteristic beginning-of-session spontaneous recovery. There was little or no extinction of NMR conditioning during cerebellar inactivation. After inactivation, the muscimol- inactivated subjects went on to acquire and extinguish NM responses at rates similar to those of appropriate controls. We conclude that cerebellar circuitry is essential for, and actively engaged in, both acquisition and extinction of this simple form of motor learning.

Animals↗