Giovanni Mirabella

Neural correlates of cognitive control of reaching movements in the dorsal premotor cortex of rhesus monkeys

Canceling a pending movement is a hallmark of voluntary behavioral control because it allows us to quickly adapt to unattended changes either in the external environment or in our thoughts. The countermanding paradigm allows the study of inhibitory processes of motor acts by requiring the subject to withhold planned movements in response to an infrequent stop-signal. At present the neural processes underlying the inhibitory control of arm movements are mostly unknown. We recorded the activity of single units in the rostral and caudal portion of the dorsal premotor cortex (PMd) of monkeys trained in a countermanding reaching task. We found that among neurons with a movement-preparatory activity, about one-third exhibit a modulation before the behavioral estimate of the time it takes to cancel a planned movement. Hence these neurons exhibit a pattern of activity suggesting that PMd plays a critical role in the brain networks involved in the control of arm movement initiation and suppression.

Deep Brain Stimulation of Subthalamic Nuclei Affects Arm Response Inhibition In Parkinson’s Patients

The precise localizations of the neural substrates of voluntary inhibition are still debated. It has been hypothesized that, in humans, this executive function relies upon a right-lateralized pathway comprising the inferior frontal gyrus and the presupplementary motor area, which would control the neural processes for movement inhibition acting through the right subthalamic nucleus (STN). We assessed the role of the right STN, via a countermanding reaching task, in 10 Parkinsons patients receiving high-frequency electrical stimulation of the STN of both hemispheres (deep brain stimulation, DBS) and in 13 healthy subjects. We compared the performance of Parkinsons patients in 4 experimental conditions: DBS-ON, DBS-OFF, DBS-OFF right, and DBS-OFF left. We found that 1) inhibitory control is improved only when both DBS are active, that is, the reaction time to the stop signal is significantly shorter in the DBS-ON condition than in all the others, 2) bilateral stimulation of STN restores the inhibitory control to a near-normal level, and 3) DBS does not cause a general improvement in task-related motor function as it does not affect the length of the reaction times of arm movements, that is, in our experimental context, STN seems to play a selective role in response inhibition.

Hippocampal, amygdala, and neocortical synchronization of theta rhythms is related to an immediate recall during Rey auditory verbal learning test

It is well known that theta rhythms (3–8 Hz) are the fingerprint of hippocampus, and that neural activity accompanying encoding of words differs according to whether the items are later remembered or forgotten [“subsequent memory effect” (SME)]. Here, we tested the hypothesis that temporal synchronization of theta rhythms among hippocampus, amygdala, and neocortex is related to immediate memorization of repeated words. To address this issue, intracerebral electroencephalographic (EEG) activity was recorded in five subjects with drug‐resistant temporal lobe epilepsy (TLE), under presurgical monitoring routine. During the recording of the intracerebral EEG activity, the subjects performed a computerized version of Rey auditory verbal learning test (RAVLT), a popular test for the clinical evaluation of the immediate and delayed memory. They heard the same list of 15 common words for five times. Each time, immediately after listening the list, the subjects were required to repeat as many words as they could recall. Spectral coherence of the intracerebral EEG activity was computed in order to assess the temporal synchronization of the theta (about 3–8 Hz) rhythms among hippocampus, amygdala, and temporal‐occipital neocortex. We found that theta coherence values between amygdala and hippocampus, and between hippocampus and occipital‐temporal cortex, were higher in amplitude during successful than unsuccessful immediate recall. A control analysis showed that this was true also for a gamma band (40–45 Hz). Furthermore, these theta and gamma effects were not observed in an additional (control) subject with drug‐resistant TLE and a wide lesion to hippocampus. In conclusion, a successful immediate recall to the RAVLT was associated to the enhancement of temporal synchronization of the theta (gamma) rhythms within a cerebral network including hippocampus, amygdala, and temporal–occipital neocortex. Hum Brain Mapp, 2009.

Should I stay or should I go? Conceptual underpinnings of goal-directed actions

All actions, even the simplest like moving an arm to grasp a pen, are associated with energy costs. Thus all mobile organisms possess the ability to evaluate resources and select those behaviors that are most likely to lead to the greatest accrual of valuable items (reward) in the near or, especially in the case of humans, distant future. The evaluation process is performed at all possible stages of the series of decisions that lead to the building of a goal-directed action or to its suppression. This is because all animals have a limited amount of energy and resources; to survive and be able to reproduce they have to minimize the costs and maximize the outcomes of their actions. These computations are at the root of behavioral flexibility. Two executive functions play a major role in generating flexible behaviors: (i) the ability to predict future outcomes of goal-directed actions; and (ii) the ability to cancel them when they are unlikely to accomplish valuable results. These two processes operate continuously during the entire course of a movement: during its genesis, its planning and even its execution, so that the motor output can be modulated or suppressed at any time before its execution. In this review, functional interactions of the extended neural network subserving generation and inhibition of goal-directed movements will be outlined, leading to the intriguing hypothesis that the performance of actions and their suppression are not specified by independent sets of brain regions. Rather, it will be proposed that acting and stopping are functions emerging from specific interactions between largely overlapping brain regions, whose activity is intimately linked (directly or indirectly) to the evaluations of pros and cons of an action. Such mechanism would allow the brain to perform as a highly efficient and flexible system, as different functions could be computed exploiting the same components operating in different configurations.

Context influences on the preparation and execution of reaching movements

The ability of rapidly adapting our motor behaviour in order to face the unpredictable changes in the surrounding environment is fundamental for survival. To achieve such a high level of efficiency our motor system has to assess continuously the context in which it acts, gathering all available information that can be relevant for planning goal-oriented movements. One still-debated aspect of movement organization is the nature and timing of motor planning. While motor plans are often taken to be concerned with the setting of kinematic parameters as a function of perceptual and motor factors, it has been suggested that higher level, cognitive factors may also affect planning. To explore this issue further, we asked 18 right-handed human participants to perform speeded hand-reaching movement toward a visual target in two different experimental settings, a reaction time (RT) paradigm (go-only task) and a countermanding paradigm. In both tasks participants executed the same movements, but in the countermanding task no-stop trials were randomly intermixed with stop trials. In stop trials participants were required to withhold the ongoing movement whenever a stop signal was shown. It is known that the presence of stop trials induces a consistent increase of the RTs of no-stop trials with respect to the RTs of go-only trials. However, nothing is known about a similar effect for movement times (MTs). We found that RTs and MTs exhibit opposing tendencies, so that a decrease in the RT correspond to an increase in the MT and vice versa. This tendency was present in all our participants and significant in 90% of them. Furthermore we found a moderate, but again very consistent, anticorrelation between RTs and MTs on a trial-by-trial base. These findings are consistent with strategic changes in movement programmes for the very same movements under different cognitive contexts, requiring different degrees of feedback-driven control during movement.

Stop-event-related potentials from intracranial electrodes reveal a key role of premotor and motor cortices in stopping ongoing movements

In humans, the ability to withhold manual motor responses seems to rely on a right-lateralized frontal–basal ganglia–thalamic network, including the pre-supplementary motor area and the inferior frontal gyrus (IFG). These areas should drive subthalamic nuclei to implement movement inhibition via the hyperdirect pathway. The output of this network is expected to influence those cortical areas underlying limb movement preparation and initiation, i.e., premotor (PMA) and primary motor (M1) cortices. Electroencephalographic (EEG) studies have shown an enhancement of the N200/P300 complex in the event-related potentials (ERPs) when a planned reaching movement is successfully stopped after the presentation of an infrequent stop-signal. PMA and M1 have been suggested as possible neural sources of this ERP complex but, due to the limited spatial resolution of scalp EEG, it is not yet clear which cortical areas contribute to its generation. To elucidate the role of motor cortices, we recorded epicortical ERPs from the lateral surface of the fronto-temporal lobes of five pharmacoresistant epileptic patients performing a reaching version of the countermanding task while undergoing presurgical monitoring. We consistently found a stereotyped ERP complex on a single-trial level when a movement was successfully cancelled. These ERPs were selectively expressed in M1, PMA, and Brodmanns area (BA) 9 and their onsets preceded the end of the stop process, suggesting a causal involvement in this executive function. Such ERPs also occurred in unsuccessful-stop (US) trials, that is, when subjects moved despite the occurrence of a stop-signal, mostly when they had long reaction times (RTs). These findings support the hypothesis that motor cortices are the final target of the inhibitory command elaborated by the frontal–basal ganglia–thalamic network.

Heterogeneous Attractor Cell Assemblies for Motor Planning in Premotor Cortex

Cognitive functions like motor planning rely on the concerted activity of multiple neuronal assemblies underlying still elusive computational strategies. During reaching tasks, we observed stereotyped sudden transitions (STs) between low and high multiunit activity of monkey dorsal premotor cortex (PMd) predicting forthcoming actions on a single-trial basis. Occurrence of STs was observed even when movement was delayed or successfully canceled after a stop signal, excluding a mere substrate of the motor execution. An attractor model accounts for upward STs and high-frequency modulations of field potentials, indicative of local synaptic reverberation. We found in vivo compelling evidence that motor plans in PMd emerge from the coactivation of such attractor modules, heterogeneous in the strength of local synaptic self-excitation. Modules with strong coupling early reacted with variable times to weak inputs, priming a chain reaction of both upward and downward STs in other modules. Such web of “flip-flops” rapidly converged to a stereotyped distributed representation of the motor program, as prescribed by the long-standing theory of associative networks.

Stimulation of subthalamic nuclei restores a near normal planning strategy in Parkinson's patients.

A fundamental function of the motor system is to gather key information from the environment in order to implement behavioral strategies appropriate to the context. Although several lines of evidence indicate that Parkinson’s disease affects the ability to modify behavior according to task requirements, it is currently unknown whether deep brain stimulation (DBS) of the subthalamic nucleus (STN) affects context-related planning. To explore this issue, we asked 12 Parkinson’s patients with bilateral STN DBS and 13 healthy subjects to execute similar arm reaching movements in two different paradigms: go-only and countermanding tasks. In the former task patients had to perform speeded reaching movements to a peripheral target. In contrast, in the countermanding task participants had to perform the same reaches unless an infrequent and unpredictable stop-signal was shown during the reaction time (RT) indicating that they should withhold the ongoing action. We compared the performance of Parkinson’s patients in different DBS conditions. We found that patients with both DBS-ON behaved similarly to healthy subjects, in that RTs of no-stop trial increased while movement times (MTs) decreased with respect to those of go-only-trials. However, when both DBS were off, both RTs and MTs were longer in no-stop trials than in go-only trials. These findings indicate that bilateral DBS of STN can partially restore the appropriate motor strategy according to the given cognitive contexts.

Processing of hand-related verbs specifically affects the planning and execution of arm reaching movements.

Even though a growing body of research has shown that the processing of action language affects the planning and execution of motor acts, several aspects of this interaction are still hotly debated. The directionality (i.e. does understanding action-related language induce a facilitation or an interference with the corresponding action?), the time course, and the nature of the interaction (i.e. under what conditions does the phenomenon occur?) are largely unclear. To further explore this topic we exploited a go/no-go paradigm in which healthy participants were required to perform arm reaching movements toward a target when verbs expressing either hand or foot actions were shown, and to refrain from moving when abstract verbs were presented. We found that reaction times (RT) and percentages of errors increased when the verb involved the same effector used to give the response. This interference occurred very early, when the interval between verb presentation and the delivery of the go signal was 50 ms, and could be elicited until this delay was about 600 ms. In addition, RTs were faster when subjects used the right arm than when they used the left arm, suggesting that action–verb understanding is left-lateralized. Furthermore, when the color of the printed verb and not its meaning was the cue for movement execution the differences between RTs and error percentages between verb categories disappeared, unequivocally indicating that the phenomenon occurs only when the semantic content of a verb has to be retrieved. These results are compatible with the theory of embodied language, which hypothesizes that comprehending verbal descriptions of actions relies on an internal simulation of the sensory–motor experience of the action, and provide a new and detailed view of the interplay between action language and motor acts.

Alpha, beta and gamma electrocorticographic rhythms in somatosensory, motor, premotor and prefrontal cortical areas differ in movement execution and observation in humans

OBJECTIVE In the present study, we tested the hypothesis that both movement execution and observation induce parallel modulations of alpha, beta, and gamma electrocorticographic (ECoG) rhythms in primary somatosensory (Brodmann area 1-2, BA1-2), primary motor (BA4), ventral premotor (BA6), and prefrontal (BA44 and BA45, part of putative human mirror neuron system underlying the understanding of actions of other people) areas. METHODS ECoG activity was recorded in drug-resistant epileptic patients during the execution of actions to reach and grasp common objects according to their affordances, as well as during the observation of the same actions performed by an experimenter. RESULTS Both action execution and observation induced a desynchronization of alpha and beta rhythms in BA1-2, BA4, BA6, BA44 and BA45, which was generally higher in amplitude during the former than the latter condition. Action execution also induced a major synchronization of gamma rhythms in BA4 and BA6, again more during the execution of an action than during its observation. CONCLUSION Human primary sensorimotor, premotor, and prefrontal areas do generate alpha, beta, and gamma rhythms and differently modulate them during action execution and observation. Gamma rhythms of motor areas are especially involved in action execution. SIGNIFICANCE Oscillatory activity of neural populations in sensorimotor, premotor and prefrontal (part of human mirror neuron system) areas represents and distinguishes own actions from those of other people. This methodological approach might be used for a neurophysiological diagnostic imaging of social cognition in epileptic patients.