Volition and conflict in human medial frontal cortex

Controversy surrounds the role of human medial frontal cortex in controlling actions. Although damage to this area leads to severe difficulties in spontaneously initiating actions, the precise mechanisms underlying such "volitional" deficits remain to be established. Previous studies have implicated the medial frontal cortex in conflict monitoring and the control of voluntary action, suggesting that these key processes are functionally related or share neural substrates. Here, we combine a novel behavioral paradigm with functional imaging of the oculomotor system to reveal, for the first time, a functional subdivision of the pre-supplementary motor area (pre-SMA) into anatomically distinct areas that respond exclusively to either volition or conflict. We also demonstrate that activity in the supplementary eye field (SEF) distinguishes between success and failure in changing voluntary action plans during conflict, suggesting a role for the SEF in implementing the resolution of conflicting actions. We propose a functional architecture of human medial frontal cortex that incorporates the generation of action plans and the resolution of conflict.     

Localization of functional regions of human mesial cortex by somatosensory evoked potential recording and by cortical stimulation

We describe methods of localizing functional regions of the mesial wall, based on 47 patients studied intraoperatively or following chronic implantation of subdural electrodes. Somatosensory evoked potentials were recorded to stimulation of posterior tibial, dorsal pudendal, median, and trigeminal nerves. Bipolar cortical stimulation was performed, and in 4 cases movement-related potentials were recorded.The cingulate and marginal sulci formed the inferior and posterior borders of the sensorimotor areas and the supplementary motor area (SMA). The foot sensory area occupied the posterior paracentral lobule, while the genitalia were represented anterior to the foot sensory area, near the cingulate sulcus. The foot motor area was anterior and superior to the sensory areas, but there was overlap in these representations. There was a rough somatotopic organization within the SMA, with the face represented anterior to the hand. However, there was little evidence of the “pre-SMA” region described in monkeys. Complex movements involving more than one extremity were elicited by stimulation of much of the SMA. The region comprising the supplementary sensory area was not clearly identified, but may involve much of the precuneus. Movement-related potentials did not provide additional localizing information, although in some recordings readiness potentials were recorded from the SMA that appeared to be locally generated.     

Neural Bases for Individual Differences in the Subjective Experience of Short Durations (Less than 2 Seconds)

The current research was designed to establish whether individual differences in timing performance predict neural activation in the areas that subserve the perception of short durations ranging between 400 and 1600 milliseconds. Seventeen participants completed both a temporal bisection task and a control task, in a mixed fMRI design. In keeping with previous research, there was increased activation in a network of regions typically active during time perception including the right supplementary motor area (SMA) and right pre-SMA and basal ganglia (including the putamen and right pallidum). Furthermore, correlations between neural activity in the right inferior frontal gyrus and SMA and timing performance corroborate the results of a recent meta-analysis and are further evidence that the SMA forms part of a neural clock that is responsible for the accumulation of temporal information. Specifically, subjective lengthening of the perceived duration were associated with increased activation in both the right SMA (and right pre-SMA) and right inferior frontal gyrus.     

Neuronal activity in the primate supplementary motor area and the primary motor cortex in relation to spatio-temporal bimanual coordination

Single neuronal activity was recorded from the supplementary motor area (SMA-proper and pre-SMA) and primary motor cortex (M1) in two Macaca fascicularis trained to perform a delayed conditional sequence of coordinated bimanual pull and grasp movements. The behavioural paradigm was designed to distinguish neuronal activity associated with bimanual coordination from that related to a comparable motor sequence but executed unimanually (left or right arm only). The bimanual and unimanual trials were instructed in a random order by a visual cue. Following the cue, there was a waiting period until presentation of a "go-signal", signalling the monkey to perform the instructed movement. A total of 143 task-related neurons were recorded from the SMA (SMA-proper, 62; pre-SMA, 81). Most SMA units (87%) were active in both unimanual contralateral and unimanual ipsilateral trials (bilateral neurons), whereas 9% of units were active only in unimanual contralateral trials and 3% were active only in unimanual ipsilateral trials. Forty-eight per cent of SMA task-related units were classified as bimanual, defined as neurons in which the activity observed in bimanual trials could not be predicted from that associated with unimanual trials when comparing the same events related to the same arm. For direct comparison, 527 neurons were recorded from M1 in the same monkeys performing the same tasks. The comparison showed that M1 contains significantly less bilateral neurons (75%) than the SMA, whereas the reverse was observed for contralateral neurons (22% in M1). The proportion of M1 bimanual cells (53%) was not statistically different from that observed in the SMA. The results suggest that both the SMA and M1 may contribute to the control of sequential bimanual coordinated movements. Interlimb coordination may then take place in a distributed network including at least the SMA and M1, but the contribution of other cortical and subcortical areas such as cingulate motor cortex and basal ganglia remains to be investigated.     

Reduced Topological Efficiency in Cortical-Basal Ganglia Motor Network of Parkinson's Disease: A Resting State fMRI Study

Parkinson''s disease (PD) is mainly characterized by dopamine depletion of the cortico-basal ganglia (CBG) motor circuit. Given that dopamine dysfunction could affect functional brain network efficiency, the present study utilized resting-state fMRI (rs-fMRI) and graph theoretical approach to investigate the topological efficiency changes of the CBG motor network in patients with PD during a relatively hypodopaminergic state (12 hours after a last dose of dopamimetic treatment). We found that PD compared with controls had remarkable decreased efficiency in the CBG motor network, with the most pronounced changes observed in rostral supplementary motor area (pre-SMA), caudal SMA (SMA-proper), primary motor cortex (M1), primary somatosensory cortex (S1), thalamus (THA), globus pallidus (GP), and putamen (PUT). Furthermore, reduced efficiency in pre-SMA, M1, THA and GP was significantly correlated with Unified Parkinson''s Disease Rating Scale (UPDRS) motor scores in PD patients. Together, our results demonstrate that individuals with PD appear to be less effective at information transfer within the CBG motor pathway, which provides a novel perspective on neurobiological explanation for the motor symptoms in patients. These findings are in line with the pathophysiology of PD, suggesting that network efficiency metrics may be used to identify and track the pathology of PD.     

Evidence for a Role of a Cortico-Subcortical Network for Automatic and Unconscious Motor Inhibition of Manual Responses

It is now clear that non-consciously perceived stimuli can bias our decisions. Although previous researches highlighted the importance of automatic and unconscious processes involved in voluntary action, the neural correlates of such processes remain unclear. Basal ganglia dysfunctions have long been associated with impairment in automatic motor control. In addition, a key role of the medial frontal cortex has been suggested by administrating a subliminal masked prime task to a patient with a small lesion restricted to the supplementary motor area (SMA). In this task, invisible masked arrows stimuli were followed by visible arrow targets for a left or right hand response at different interstimuli intervals (ISI), producing a traditional facilitation effect for compatible trials at short ISI and a reversal inhibitory effect at longer ISI. Here, by using fast event-related fMRI and a weighted parametric analysis, we showed BOLD related activity changes in a cortico-subcortical network, especially in the SMA and the striatum, directly linked to the individual behavioral pattern. This new imaging result corroborates previous works on subliminal priming using lesional approaches. This finding implies that one of the roles of these regions was to suppress a partially activated movement below the threshold of awareness.     

Assessment of brain interactivity in the motor cortex from the concept of functional connectivity and spectral analysis of fMRI data

Functional magnetic resonance imaging (fMRI) was used to assess the contributions of movement preparation and execution of a visuomotor task in a cerebral motor network. The functional connectivity of the voxel time series between brain regions in the frequency space was investigated by performing spectral analysis of fMRI time series. The regional interactivities between the two portions of the supplementary motor area (pre-SMA and SMA-proper) and the primary motor cortex (M1), defined as a seed region, were evaluated. The spectral parameter of coherence was used to describe a correlation structure in the frequency domain between two voxel-based time series and to infer the strength of the functional interaction within our presumed motor network of connections. The results showed meaningful differences of the functional interactions between the two portions of the SMA and the M1 area depending on the task conditions. This approach demonstrated the existence of a functional dissociation between the pre-SMA and SMA-proper subregions. We therefore conclude that spectral analysis is useful for identifying functional interactions of brain regions and might provide a powerful tool to quantify changes in connectivity profiles associated with various components of an experimental task.     

Individual differences in subconscious motor control predicted by GABA concentration in SMA

Subliminal visual stimuli affect motor planning, but the size of such effects differs greatly between individuals. Here, we investigated whether such variation may be related to neurochemical differences between people. Cortical responsiveness is expected to be lower under the influence of more of the main inhibitory neurotransmitter, GABA. Thus, we hypothesized that, if an individual has more GABA in the supplementary motor area (SMA)--a region previously associated with automatic motor control--this would result in smaller subliminal effects. We measured the reversed masked prime--or negative compatibility--effect, and found that it correlated strongly with GABA concentration, measured with magnetic resonance spectroscopy. This occurred specifically in the SMA region, and not in other regions from which spectroscopy measurements were taken. We replicated these results in an independent cohort: more GABA in the SMA region is reliably associated with smaller effect size. These findings suggest that, across individuals, the responsiveness of subconscious motor mechanisms is related to GABA concentration in the SMA.     

Parkinson-Related Changes of Activation in Visuomotor Brain Regions during Perceived Forward Self-Motion

Radial expanding optic flow is a visual consequence of forward locomotion. Presented on screen, it generates illusionary forward self-motion, pointing at a close vision-gait interrelation. As particularly parkinsonian gait is vulnerable to external stimuli, effects of optic flow on motor-related cerebral circuitry were explored with functional magnetic resonance imaging in healthy controls (HC) and patients with Parkinson’s disease (PD). Fifteen HC and 22 PD patients, of which 7 experienced freezing of gait (FOG), watched wide-field flow, interruptions by narrowing or deceleration and equivalent control conditions with static dots. Statistical parametric mapping revealed that wide-field flow interruption evoked activation of the (pre-)supplementary motor area (SMA) in HC, which was decreased in PD. During wide-field flow, dorsal occipito-parietal activations were reduced in PD relative to HC, with stronger functional connectivity between right visual motion area V5, pre-SMA and cerebellum (in PD without FOG). Non-specific ‘changes’ in stimulus patterns activated dorsolateral fronto-parietal regions and the fusiform gyrus. This attention-associated network was stronger activated in HC than in PD. PD patients thus appeared compromised in recruiting medial frontal regions facilitating internally generated virtual locomotion when visual motion support falls away. Reduced dorsal visual and parietal activations during wide-field optic flow in PD were explained by impaired feedforward visual and visuomotor processing within a magnocellular (visual motion) functional chain. Compensation of impaired feedforward processing by distant fronto-cerebellar circuitry in PD is consistent with motor responses to visual motion stimuli being either too strong or too weak. The ‘change’-related activations pointed at covert (stimulus-driven) attention.     

What's next? Sequential movement encoding in primary motor cortex

Complex actions often can be decomposed into sequences of individual movements. Primate medial motor areas (SMA and pre-SMA) have been shown to be key players in the concert of such sequential actions. In this issue of Neuron, Lu and Ashe show for the first time that neurons in primate M1-the ultimate output stage of cortex-have anticipatory activity related to specific movement sequences. These findings challenge the traditional view of M1 as being a simple module for generating movements.     

Neuronal correlates of kinematics-to-dynamics transformation in the supplementary motor area

It is widely acknowledged that movements are planned at the level of the kinematics. However, the central nervous system must ultimately transform kinematic plans into dynamics-related commands. How, when, and where the kinematics-to-dynamics (KD) transformation is processed represent fundamental and unanswered questions. We recorded from the supplementary motor area (SMA) of two monkeys as they executed visually instructed reaching movements. We specifically analyzed a delay period following the instruction but prior to the go signal (motor planning). During the delay, a group of neurons in the SMA progressively came to reflect the dynamics rather than the desired kinematics of the upcoming movement. This finding suggests that some neurons in the SMA participate in the KD transformation.     

The Human Frontal Oculomotor Cortical Areas Contribute Asymmetrically to Motor Planning in a Gap Saccade Task

Background

Saccadic eye movements are used to rapidly align the fovea with the image of objects of interest in peripheral vision. We have recently shown that in children there is a high preponderance of quick latency but poorly planned saccades that consistently fall short of the target goal. The characteristics of these multiple saccades are consistent with a lack of proper inhibitory control of cortical oculomotor areas on the brainstem saccade generation circuitry.

Methodology/Principal Findings

In the present paper, we directly tested this assumption by using single pulse transcranial magnetic stimulation (TMS) to transiently disrupt neuronal activity in the frontal eye fields (FEF) and supplementary eye fields (SEF) in adults performing a gap saccade task. The results showed that the incidence of multiple saccades was increased for ispiversive but not contraversive directions for the right and left FEF, the left SEF, but not for the right SEF. Moreover, this disruption was most substantial during the ∼50 ms period around the appearance of the peripheral target. A control condition in which the dorsal motor cortex was stimulated demonstrated that this was not due to any non-specific effects of the TMS influencing the spatial distribution of attention.

Conclusions/Significance

Taken together, the results are consistent with a direction-dependent role of the FEF and left SEF in delaying the release of saccadic eye movements until they have been fully planned.     

Comparison of neural activity in the supplementary motor area and in the primary motor cortex in monkeys.

Neuronal activity recorded from the primary motor cortex (MI) and from the supplementary motor area (SMA) was compared in two monkeys trained to perform conditioned arm movements. A handle had to be held in a central waiting position until a visual go and cueing signal indicated to the monkey to move the handle either to a medial or to a lateral target zone (choice reaction time paradigm). Unit and representative electromyographic data were analyzed in relation either to the go signal or to movement onset. In 240 penetrations, 431 SMA neurons and 353 MI neurons were found with activity related to the task. The majority of neurons (303 in MI, 290 in SMA) displayed activity changes after the go signal and before movement onset. Of these "short-lead neurons", 71% in MI and 41% in SMA were clearly related to movement execution. The distribution of lead times in MI and SMA neurons was completely overlapping without any statistical difference among subgroups. The remaining neurons were as well related to the go signal as to movement onset, or were better related to the visual go signal. The response latencies to this signal were not statistically different in SMA and MI neurons. Activity changes during the waiting period was observed more frequently in SMA (47%) than in MI (32%); modulations restricted to the waiting period occurred in 14% of SMA neurons, but were exceptional in MI neurons (3%). It is concluded from these experiments that a surprisingly large proportion of SMA neurons have "MI-like" properties, in that they are temporally recruited together with MI neurons, with similar patterns of discharges during the task. This then suggests that the two interconnected areas operate in parallel. A population of SMA neurons is involved in some processing that is not as predominantly expressed in MI. This activity could relate to sensory, timing, or other higher-order aspects of response preparation, and/or motor functions such as postural stabilization.     

Functional MRI evaluation of supplementary motor area language dominance in right- and left-handed subjects

Functional magnetic resonance imaging (fMRI) is a non-invasive brain imaging technique widely used in the evaluation of the brain function that provides images with high temporal and spatial resolution. Investigation of the supplementary motor area (SMA) function is critical in the pre-surgical evaluation of neurological patients, since marked individual differences and complex overlapping with adjacent cortical areas exist, and it is important to spare the SMA from lesions when adjacent cortical tissue is surgically removed. We used fMRI to assess the activity of SMA in six right-handed and six left-handed healthy volunteers when a task requiring silent repetition of a series of words was given. Brain activation areas in each of the subjects were localized according to the standard Talairach coordinate space, and the individual voxels for each map were compared after 3D sagittal images were created and SMA was delimited. Quantitative analysis of hemispheric and bilateral SMA activation was described as mean ± standard deviation of hot points/total points. The results show that the language task induced bilateral SMA activation. Left SMA activation was significantly higher than right SMA activation in both right-handed and left-handed subjects.     

Disrupting the experience of control in the human brain: pre-supplementary motor area contributes to the sense of agency

The feeling of controlling events through one''s actions is fundamental to human experience, but its neural basis remains unclear. This ‘sense of agency’ (SoA) can be measured quantitatively as a temporal linkage between voluntary actions and their external effects. We investigated the brain areas underlying this aspect of action awareness by using theta-burst stimulation to locally and reversibly disrupt human brain function. Disruption of the pre-supplementary motor area (pre-SMA), a key structure for preparation and initiation of a voluntary action, was shown to reduce the temporal linkage between a voluntary key-press action and a subsequent electrocutaneous stimulus. In contrast, disruption of the sensorimotor cortex, which processes signals more directly related to action execution and sensory feedback, had no significant effect. Our results provide the first direct evidence of a pre-SMA contribution to SoA.     

Effects of reversible inactivation of the supplementary motor area (SMA) on unimanual grasp and bimanual pull and grasp performance in monkeys

Abstract The supplementary motor area (SMA) was reversibly inactivated by muscimol microinfusion in two monkeys while they were performing two motor tasks: (1) a delayed conditional bimanual drawer pulling and grasping sequence which was initiated on a self-paced basis; (2) a unimanual reach and grasp task (modified Kluver board task). Unilateral or bilateral inactivation of the SMA induced a prominent deficit in trial initiation of bimanual sequential movements, affecting the hand contralateral to the inactivated side or both hands, respectively. The deficit was a long lasting (10-15 min or more) inability of the monkey to place its hand (s) in the ready position on start touch-sensitive pads, a condition required to initiate the drawer task. However, if after such a deficit period, the experimenter put his hand on the start touch-sensitive pad to initiate the trial, then the monkey executed the drawer task without obvious motor deficit. SMA inactivation did not affect unimanual reaching and grasping movements in the board task. In contrast to the SMA, inactivation of other motor areas (primary, premotor dorsal, anterior intraparietal area) did not affect the initiation of movement sequences in the drawer task. These data thus indicate that the SMA plays a crucial and specific role in initiation of self-paced movement sequences. However, SMA inactivation did not prevent the monkeys to perform coordinated movements of the two forelimbs and hands, indicating that SMA is not necessary for bimanual coordination.     

Differential Effects of Motor Efference Copies and Proprioceptive Information on Response Evaluation Processes

It is well-kown that sensory information influences the way we execute motor responses. However, less is known about if and how sensory and motor information are integrated in the subsequent process of response evaluation. We used a modified Simon Task to investigate how these streams of information are integrated in response evaluation processes, applying an in-depth neurophysiological analysis of event-related potentials (ERPs), time-frequency decomposition and sLORETA. The results show that response evaluation processes are differentially modulated by afferent proprioceptive information and efference copies. While the influence of proprioceptive information is mediated via oscillations in different frequency bands, efference copy based information about the motor execution is specifically mediated via oscillations in the theta frequency band. Stages of visual perception and attention were not modulated by the interaction of proprioception and motor efference copies. Brain areas modulated by the interactive effects of proprioceptive and efference copy based information included the middle frontal gyrus and the supplementary motor area (SMA), suggesting that these areas integrate sensory information for the purpose of response evaluation. The results show how motor response evaluation processes are modulated by information about both the execution and the location of a response.     

Neuronal correlates of metacognition in primate frontal cortex

Humans are metacognitive: they monitor and control their cognition. Our hypothesis was that neuronal correlates of metacognition reside in the same brain areas responsible for cognition, including frontal cortex. Recent work demonstrated that nonhuman primates are capable of metacognition, so we recorded from single neurons in the frontal eye field, dorsolateral prefrontal cortex, and supplementary eye field of monkeys (Macaca mulatta) that performed a metacognitive visual-oculomotor task. The animals made a decision and reported it with a saccade, but received no immediate reward or feedback. Instead, they had to monitor their decision and bet whether it was correct. Activity was correlated with decisions and bets in all three brain areas, but putative metacognitive activity that linked decisions to appropriate bets occurred exclusively in the SEF. Our results offer a survey of neuronal correlates of metacognition and implicate the SEF in linking cognitive functions over short periods of time.     

Evidence for human fronto-central gamma activity during long-term memory encoding of word sequences

Although human gamma activity (30-80 Hz) associated with visual processing is often reported, it is not clear to what extend gamma activity can be reliably detected non-invasively from frontal areas during complex cognitive tasks such as long term memory (LTM) formation. We conducted a memory experiment composed of 35 blocks each having three parts: LTM encoding, working memory (WM) maintenance and LTM retrieval. In the LTM encoding and WM maintenance parts, participants had to respectively encode or maintain the order of three sequentially presented words. During LTM retrieval subjects had to reproduce these sequences. Using magnetoencephalography (MEG) we identified significant differences in the gamma and beta activity. Robust gamma activity (55-65 Hz) in left BA6 (supplementary motor area (SMA)/pre-SMA) was stronger during LTM rehearsal than during WM maintenance. The gamma activity was sustained throughout the 3.4 s rehearsal period during which a fixation cross was presented. Importantly, the difference in gamma band activity correlated with memory performance over subjects. Further we observed a weak gamma power difference in left BA6 during the first half of the LTM rehearsal interval larger for successfully than unsuccessfully reproduced word triplets. In the beta band, we found a power decrease in left anterior regions during LTM rehearsal compared to WM maintenance. Also this suppression of beta power correlated with memory performance over subjects. Our findings show that an extended network of brain areas, characterized by oscillatory activity in different frequency bands, supports the encoding of word sequences in LTM. Gamma band activity in BA6 possibly reflects memory processes associated with language and timing, and suppression of beta activity at left frontal sensors is likely to reflect the release of inhibition directly associated with the engagement of language functions.     

A neural correlate of oculomotor sequences in supplementary eye field

Complex learned motor sequences can be composed of a combination of a small number of elementary actions. To investigate how the brain represents such sequences, we devised an oculomotor sequence task in which the monkey had to choose the target solely by the sequential context, not by the current stimulus combination. We found that many neurons in the supplementary eye field (SEF) became active with a specific target direction (D neuron) or a specific target/distractor combination (C neuron). Furthermore, such activity was often selective for one among several sequences that included the combination (S neuron). These results suggest that the SEF contributes to the generation of saccades in many learned sequences.