Conditional Motor Task Research Articles

Cholinergic interneuron characteristics and nicotinic properties in the striatum.

The neostriatum (dorsal striatum) is composed of the caudate and putamen. The ventral striatum is the ventral conjunction of the caudate and putamen that merges into and includes the nucleus accumbens and striatal portions of the olfactory tubercle. About 2% of the striatal neurons are cholinergic. Most cholinergic neurons in the central nervous system make diffuse projections that sparsely innervate relatively broad areas. In the striatum, however, the cholinergic neurons are interneurons that provide very dense local innervation. The cholinergic interneurons provide an ongoing acetylcholine (ACh) signal by firing action potentials tonically at about 5 Hz. A high concentration of acetylcholinesterase in the striatum rapidly terminates the ACh signal, and thereby minimizes desensitization of nicotinic acetylcholine receptors. Among the many muscarinic and nicotinic striatal mechanisms, the ongoing nicotinic activity potently enhances dopamine release. This process is among those in the striatum that link the two extensive and dense local arbors of the cholinergic interneurons and dopaminergic afferent fibers. During a conditioned motor task, cholinergic interneurons respond with a pause in their tonic firing. It is reasonable to hypothesize that this pause in the cholinergic activity alters action potential dependent dopamine release. The correlated response of these two broad and dense neurotransmitter systems helps to coordinate the output of the striatum, and is likely to be an important process in sensorimotor planning and learning.

Action of Dopaminergic Agents on the Impulse Activity of Sensorimotor Cortex Neurons of Cats Performing a Conditioned Motor Task

We demonstrate that dopamine itself, a selective dopamine D1 receptor agonist, SKF 38393, and a selective dopamine D2 receptor agonist, quinpirole, exert both facilitatory and suppressive effects on neuronal activity in the sensorimotor cortex of the cat, which is related to a conditioned movement. These effects are mediated by activation of dopamine receptors. Our data can be used for understanding the mechanisms underlying modulation of the excitability of central neurons during various behavioral events under the influence of dopamine.

Comparison of Auditory, Somatosensory, and Visually Instructed and Internally Generated Finger Movements: A PET Study

We sought to determine how the pattern of cerebral activation, and in particular in frontal motor areas, during the performance of conditional motor tasks is dependent upon the modality of instruction (visual, auditory, or somatosensory). Regional cerebral blood flow (rCBF) changes with externally instructed movements were also compared with internally generated, self-paced, movements. We used positron emission tomography (PET) with the tracer H215O to measure rCBF in 22 healthy volunteers. External stimuli consisted of the randomized presentation of single or double impulses using a single modality for each condition. In the movement scans, the subjects used the index and middle fingers of their right hands to press a left button for a single and a right button for a double impulse, respectively. In the control scans, subjects were required to covertly distinguish a single from a double stimulus without a motor response. Data were analyzed using conventional subtraction techniques with a statistical threshold of Z > 2.33 with corrections for multiple comparisons. When the activation differences between the three externally instructed movement conditions were statistically compared, nonsignificant trends toward increased rCBF in the sensory cortex of the modality of the cue were observed but no differential activity in cortical motor areas. Internally generated movements, when compared to externally triggered movements, were associated with enhanced activation in bilateral medial and lateral premotor, dorsolateral prefrontal and superior parietal regions, largely confirming previous reports. The data indicate that, on a regional level, modality-specific processing in a conditional motor task does not occur in frontal motor areas and is probably confined to sensory areas.

Functional magnetic resonance imaging of the human motor cortex before and after whole-hand afferent electrical stimulation.

Electrical stimulation of the whole hand using a mesh-glove has been shown to improve volitional movement of the hand and arm, and decrease muscle hypertonia after hemispherical stroke in patients who have reached a recovery plateau. The goal of this study was to investigate the effect of stimulation of the nerve afferents of the hand on brain cortical activity elicited by whole-hand subthreshold stimulation for sensation in humans with intact nervous systems. Brain cortical activity in 6 healthy subjects (30-45 years) was studied using blood oxygenation level-dependent functional Magnetic Resonance Imaging during a test motor task, finger-to-thumb tapping and after 20 minutes of mesh-glove stimulation of the resting hand prior to performance of an identical motor task, to test the changes in the conditioned motor task established after 20 minutes of mesh-glove stimulation. Fifteen contiguous echo-planar sequences parallel to the bicommissural plane were acquired for functional magnetic resonance. Post-processing of image data included correction of motion artefacts and calculation of correlation coefficients between the signal intensity of pixels during rest and finger tapping and a rectangular reference wave function. The functional Magnetic Resonance Imaging examinations revealed a signal increase in the primary and secondary motor and somatosensory areas when comparing the number of activated pixels during test and conditioned motor tasks. Our preliminary study indicated that change occurred in a definite pattern in the region of the regional cerebral blood flow of the brain cortex after mesh-glove whole-hand stimulation at the subthreshold level for sensation. We assumed that this increase in regional cerebral blood flow also reflected augmented neuronal activity.

Activation of contralateral premotor cortex and medial wall motor areas of humans in an auditory conditional motor task detected by MRI

Epilepsy is associated with disruption of integration in distributed networks, together with altered localization for functions such as expressive language. The relation between atypical network connectivity and altered localization is unknown. In the current study we tested whether atypical expressive language laterality was associated with the alteration of large-scale network integration in children with medically-intractable localization-related epilepsy (LRE). Twenty-three right-handed children (age range 8–17) with medically-intractable LRE performed a verb generation task in fMRI. Language network activation was identified and the Laterality index (LI) was calculated within the pars triangularis and pars opercularis. Resting-state data from the same cohort were subjected to independent component analysis. Dual regression was used to identify associations between resting-state integration and LI values. Higher positive values of the LI, indicating typical language localization were associated with stronger functional integration of various networks including the default mode network (DMN). The normally symmetric resting-state networks showed a pattern of lateralized connectivity mirroring that of language function. The association between atypical language localization and network integration implies a widespread disruption of neural network development. These findings may inform the interpretation of localization studies by providing novel insights into reorganization of neural networks in epilepsy.

Parietal cortex and movement. I. Movement selection and reaching.

Recording studies in the parietal cortex have demonstrated single-unit activity in relation to sensory stimulation and during movement. We have performed three experiments to assess the effect of selective parietal lesions on sensory motor transformations. Animals were trained on two reaching tasks: reaching in the light to visual targets and reaching in the dark to targets defined by arm position. The third task assessed non-standard, non-spatial stimulus response mapping; in the conditional motor task animals were trained to either pull or turn a joystick on presentation of either a red or a blue square. We made two different lesions in the parietal cortex in two groups of monkeys. Three animals received bilateral lesions of areas 5, 7b and MIP, which have direct connections with the premotor and motor cortices. The three other animals subsequently received bilateral lesions in areas 7a, 7ab and LIP. Both groups were still able to select between movements arbitrarily associated with non-spatial cues in the conditional motor task. Removal of areas 7a, 7ab and LIP caused marked inaccuracy in reaching in the light to visual targets but had no effect on reaching in the dark. Removal of areas 5, 7b and MIP caused misreaching in the dark but had little effect on reaching in the light. The results suggest that the two divisions of the parietal cortex organize limb movements in distinct spatial coordinate systems. Area 7a/7ab/LIP is essential for spatial coordination of visual motor transformations. Area 5/7b/MIP is essential for the spatial coordination of arm movements in relation to proprioceptive and efference copy information. Neither part of the parietal lobe appears to be important for the non-standard, non-spatial transformations of response selection.

Visually guided saccade versus eye-hand reach: contrasting neuronal activity in the cortical supplementary and frontal eye fields.

1. We studied neuronal activity in the supplementary eye field (SEF) and frontal eye field (FEF) of a monkey during performance of a conditional motor task that required capturing of a target either with a saccadic eye movement (the saccade-only condition) or with an eye-hand reach (the saccade-and-reach condition), according to visual instructions. 2. Among 106 SEF neurons that showed presaccadic activity, more than one-half of them (54%) were active preferentially under the saccade-only condition (n = 12) or under the saccade-and-reach condition (n = 45), while the remaining 49 neurons were equally active in both conditions. 3. By contrast, most (97%) of the 109 neurons in the FEF exhibited approximately equal activity in relation to saccades under the two conditions. 4. The present results suggest the possibility that SEF neurons, at least in part, are involved in signaling whether the motor task is oculomotor or combined eye-arm movements, whereas FEF neurons are mostly related to oculomotor control.

Dopamine and complex sensorimotor integration: Further studies in a conditioned motor task in the rat

Rats were trained to depress a lever and wait for the onset of a light stimulus, occurring after four equiprobable and variable intervals. At the stimulus onset, they had to release the lever within a reaction time limit for food reinforcement. This paradigm required time estimation of the various intervals and high attentional load for correct performance. Following activation of the dopaminergic transmission after systemic injection of d-amphetamine (0.6 and 0.8 mg/kg) or intrastriatal injection of dopamine (2.5 microgram/microliters), the rat's performance was impaired. Compared with control animals, the performance deficits were expressed as an increased number of premature lever releases before the conditional stimulus onset ("premature responses") and decreased reaction times. Indeed, the reaction times distribution was shifted to the left towards shortened reaction times. Although the number of premature responses was increased, the time estimation of the four different equiprobable intervals was not disturbed after stimulation of dopaminergic activity. A delay-dependent shortening of reaction times as a result of the conditional probability of the stimulus occurrence (i.e. reaction times are shorter as the duration of the delay increases) was found in control and drug sessions, indicating that the animals were still able to prepare their motor response (lever release) even after overstimulation of the dopaminergic transmission. In contrast, blocking dopamine receptors with the selective D2 antagonist raclopride was found to induce opposite effects on the reaction time performance. The number of delayed responses (i.e. occurring with a latency > 600 ms) was found to be significantly enhanced. Furthermore, the reaction times distribution showed a shift of the values to the right revealing a general tendency to lengthened reaction times. These results indicate that a "critical level" of dopamine activity (neither too low nor too high) in the striatum is necessary for a correct execution of the movement in a conditioned motor task with temporal constraint. Moreover, while delayed responses might reflect a motor impairment, anticipatory responses might reflect a "motor facilitation" revealed by a higher level of motor readiness, without disturbing time estimation nor attentional processes.

GABA-receptor activation in the globus pallidus and entopeduncular nucleus: opposite effects on reaction time performance in the cat.

The possible role of GABAergic mechanisms in the control of the basal ganglia output structures, the globus pallidus (GP) and the entopeduncular nucleus (EP), was studied in cats performing a conditioned flexion movement triggered by an auditory stimulus. The effects of discrete unilateral microinjections of low doses of the GABAA receptor agonist (muscimol 5-100 ng/0.5 microliter) and antagonist (bicuculline methiodide 25-150 ng/0.5 microliter) in the GP and the EP were tested on the motor performance of eight animals trained to release a lever in a simple reaction time (RT) schedule after an auditory stimulus. Control injections in neighboring structures did not induce any effect except with five- to tenfold higher doses in the closest injection sites. The dose of 20 ng muscimol injected into the ventral and medial part of the GP produced an arrest of the performance after a few unsuccessful trials (over the RT reinforcement limit of 500 ms), while muscimol injected in sites located in the lateral GP resulted in a dose-dependent lengthening in RTs, with a concomitant increase in the force change latency. In most of the subjects, the force exerted on the lever was higher after muscimol than after vehicle injection. Force change velocity was then significantly increased. In contrast, muscimol injected in the ventral and rostral region of the EP produced a decrease in RTs or a complete cessation of responding after a high number of anticipatory responses (release of the lever before the trigger stimulus). No significant changes in the force change latency could be observed while there was a non-significant tendency for the force levels to be lowered. Bicuculline injections in the EP were found to increase RTs with a concomitant increase in force change latency and a slowness of velocity, while no significant effect was observed following injections in the GP. These results suggest that a balance between GABAergic activity in the two output nuclei of the basal ganglia, the GP and the EP, is crucial for the correct initiation and execution of the conditioned motor task.

Neuronal activity in the primate supplementary, pre-supplementary and premotor cortex during externally and internally instructed sequential movements

This study recorded the activity of neurons in the (i) supplementary motor area (SMA), (ii) pre-SMA (the motor area immediately rostral to the SMA), (iii) premotor cortex (PMC) and (iv) primary motor cortex (MI), while the monkey performed a conditional sequential motor task that ensures sequencing of multiple movements to the same manipulandum. This paradigm was chosen in order to prevent the participation of spatial cues in prompting the correct motor sequence. Three different movements (turn-push-pull) were performed under two task conditions: (i) internally determined (I): the monkey had to generate a pre-determined sequence from memory and without visual guidance; (ii) externally triggered (E): the correct sequence of movements was performed by following lights illuminated one after the other. Neuronal activity during the following periods were analyzed: instruction (300 ms following the onset of the auditory instruction signal); delay (interval between the end of the instruction period or the termination of the previous movement and the movement trigger); premovement (interval between the trigger signal and the movement onset); movement (interval between the mechanically-sensed movement onset and the completion of the movement) and reward (500 ms period centered at the time of reward delivery). Pre-SMA neurons were generally more active during the delay and premovement as compared to the movement, instruction and reward periods. Activity in the pre-SMA was more related to E during the pre-movement period, but exhibited a preferential relationship to I in the movement period. SMA neurons were more active when the sequential motor task was internally generated. By contrast, PMC neurons were more active when the sequence was visually guided. Such preferential activity was rarely found in MI neurons.

Selective effects of low-dose D2 dopamine receptor antagonism in a reaction-time task in rats.

Operant responses involving a cued discrimination are sensitively disrupted by neuroleptic drugs that block dopamine (DA) receptors in the brain; however, it is not clear which DA receptor subtypes may be involved in these effects. The role of D1 or D2 DA receptor antagonists on the execution of a conditioned reaction-time (RT) motor task was investigated in the present study. Rats were trained to release a lever after the presentation of a visual cue within a RT limit to be reinforced by a food pellet. The D1 receptor antagonist SCH-23390, at doses that significantly decrease the behavioral effects of cocaine, did not impair performance at any dose (5, 10, or 20 micrograms/kg) injected subcutaneously. In contrast, a selective D2 receptor antagonist raclopride (50, 100, or 200 micrograms/kg) induced a dose-dependent increase in the number of incorrect responses (release of the lever over the RT limit) associated with an increase in the RT. The results suggest that the dopaminergic nigrostriatal system, which has previously been shown to be specifically involved in this RT task (Amalric and Koob 1987), appears to be a sensitive site for sensorimotor integration, and that the execution of the conditioned RT motor task may depend preferentially on the activation of the dopaminergic D2 receptors in this system.

Neuronal activity in the motor and premotor cortices before and after learning the associations between auditory stimuli and motor responses

In order to assess the effect of learning a conditional motor task on set-related cells of the precentral cortex we recorded a total of 228 task-related cells in awake, behaving primate. A first sample of 54 set-related cells was recorded while the monkey was performing at 54.7±7.8% and a second sample of 119 set-related cells was recorded at the same stereotaxic coordinates while he was performing at 77.2±8.7%. After the monkey had learned the association between an auditory signal and a motor response we found a significant increase in the proportion and activity of directional set-related cells in the premotor cortex. Furthermore the proportion of short-latency set-related cells was found to increase in this area. None of those changes were observed in the motor cortex.

GABAergic mechanisms in the cat red nucleus: Effects of intracerebral microinjections of muscimol or bicuculline on a conditioned motor task

Interneurons in the Red Nucleus (RN) are known to be under cortical control and to exert an inhibitory action, mediated by GABAergic mechanisms, on the main output towards the spinal cord. The effects of discrete injections of a GABA receptor agonist (muscimol) or an antagonist (bicuculline) in the Red Nucleus were tested on a motor task performed by seven cats. The subjects were trained to release a lever with a flexion movement of the forelimb controlled by a reaction time (RT) paradigm. Muscimol as well as bicuculline increased RTs in a dose-dependent manner at doses below 100 ng. However the parameters of the force exerted on the lever were differentially altered by the two drugs. Muscimol increased RTs by slowing down the force change preceding movement as well as slightly delaying its latency. While bicuculline increased drastically the force change latency. It could also speed up the force change velocity for low doses. At higher doses (up to 500 ng) both drugs produced an arrest of the performance either associated with anxiety signs (bicuculline) or dystonic movements of the head followed by body rotations (muscimol). The strong motor impairments as well as the disruption of the conditioned performances following muscimol or bicuculline microinjection in the RN suggest an important functional role for GABAergic interneurons. Under the control of cortical afferences they can modulate rubrospinal activity and participate in the triggering of a conditioned movement.

Premotor cortex in the rat.

Donoghue and Wise (1982) identified an area AGm in the rat that they take to be a nonprimary motor area. In the present experiments, therefore, this area was removed bilaterally in rats. The animals were poor at relearning a visual conditional motor task but were able to learn spatial delayed alternation as rapidly as unoperated animals. Thus removing this area in rats has a similar effect to removing premotor cortex in monkeys. It is argued that this dorsomedial shoulder area should not be regarded as part of prefrontal cortex in the rat.

Premotor cortex and the conditions for movement in monkeys ( Macaca fascicularis)

Cortical association areas direct their influence on motor cortex via premotor and supplementary motor cortex. In the present experiment premotor cortex was removed bilaterally in monkeys. The monkeys were unable to relearn a visual conditional motor task on which the correct action is specified by visual cues. It was shown that the same monkeys were able to learn a non-motor visual conditional task on which the visual cues specified which object should be chosen. It is concluded that the monkeys are only impaired when they must recall a movement from memory on the basis of a visual cue.

Functional metabolic mapping of a conditioned motor task in primates utilizing 2-[ 14C]deoxyglucose

The quantitative 2-[ 14C]deoxyglucose (2DG) technique was used to compute the local cerebral metabolic rate for glucose ( l-CMRg) in motor, visual, and auditory regions of five Macacca mulatta monkeys. Three animals (controls) were injected with 2DG and sat quietly in a primate chair for 45 min. The other two animals were injected with 2DG and pulled a 0.454-kg (1-pound) weight 12 cm repetitively for 45 min with their right arm. In the control group, there were no significant differeces ( P > 0.1) in l-CMRg between homologous regions in the right and left hemispheres. The mean values of l-CMRg in homologous regions among the control animals did not differ significantly ( P > 0.1). There were large bilateral differences in l-CMRg between right and left motor structures of both operantly conditioned monkeys. Motor structures on the left side (contralateral to the working arm) demonstrated l-CMRg values that were consistently greater than right-side structures (ipsilateral to the working arm). The left-side motor structures of both working monkeys were significantly different compared with the control mean of these same structures ( P < 0.05). In the operantly conditioned animals there were no differences in l-CMRg between right and left visual and auditory structures. However, visual and auditory region showed increases in l-CMRg compared with control values, but these increases were less than those exhibited by motor regions. This study demonstrated the value of the quantitative 2DG technique in the study of functional neuroanatomic relationships during an operantly conditioned paradigm.

Single unit activity in a border area between the dorsal prefrontal and premotor regions in the visually conditioned motor task of monkeys

Single unit activity in a border area between the dorsal prefrontal and premotor regions in the visually conditioned motor task of monkeys