Inhibition of the anterior intraparietal area and the dorsal premotor cortex interfere with arbitrary visuo-motor mapping

ObjectiveThe contribution of the human anterior intraparietal area and the dorsal premotor cortex to arbitrary visuo-motor mapping during grasping were tested.MethodsTrained right-handed subjects reached for and pincer-grasped a cube with the right hand in the absence of visual feedback after the cube location had been displayed for 200 ms. During the reaching movements, the colour of the cube changed and visual feedback about the change of colour was provided for 100 ms at 500 ms after movement onset (at the time of peak grasp aperture). Depending on colour, subjects were instructed to either pincer-grasp the cube in a horizontal or vertical grasp position with the latter necessitating wrist rotation (experiment 1) or to pincer-grasp and transport the cube to either a left or right target position (experiment 2). Within two consecutive 200 ms time windows (TMS 1 and 2) starting 500 ms and 700 ms after movement onset, respectively, double pulses of supra-threshold transcranial magnetic stimulation (inter-stimulus interval: 100 ms) were delivered over (i) the left primary motor cortex (90° vertically angulated coil position, control stimulation), (ii) the left dorsal premotor cortex or (ii) the left anterior intraparietal area.ResultsCompared to control stimulation, stimulation of the anterior intraparietal area, but not of the dorsal premotor cortex, at TMS 1 delayed the times to wrist rotation (experiment 1) and hand transport (experiment 2). Compared to control stimulation, stimulation of the dorsal premotor cortex, but not of the anterior intraparietal area, at TMS 2 delayed both wrist rotation (experiment 1) and hand transport (experiment 2).ConclusionsWe contend that the anterior intraparietal area and the dorsal premotor cortex are both involved albeit at different phases during the mapping of arbitrary visual cues with goal directed grasp and transport movements.SignificanceThese data add to the current understanding of how human cortical areas work in concert during manual activities.     

Charting the excitability of premotor to motor connections while withholding or initiating a selected movement

In 19 healthy volunteers, we used transcranial magnetic stimulation (TMS) to probe the excitability in pathways linking the left dorsal premotor cortex and right primary motor cortex and those linking the left and right motor cortex during the response delay and the reaction time period while subjects performed a delayed response [symbol 1 (S1) - symbol 2 (S2)] Go-NoGo reaction time task with visual cues. Conditioning TMS pulses were applied to the left premotor or left motor cortex 8 ms before a test pulse was given to the right motor cortex at 300 or 1800 ms after S1 or 150 ms after S2. S1 coded for right-hand or left-hand movement, and S2 for release or stopping the prepared movement. Conditioning of the left premotor cortex led to interhemispheric inhibition at 300 ms post-S1, interhemispheric facilitation at 150 ms post-S2, and shorter reaction times in the move-left condition. Conditioning of the left motor cortex led to inhibition at 1800 ms post-S1 and 150 ms post-S2, and slower reaction times for move-right conditions, and inhibition at 300 and 1800 ms post-S1 for move-left conditions. Relative motor evoked potential amplitudes following premotor conditioning at 150 ms post-S2 were significantly smaller in 'NoGo' than in 'Go' trials for move-left instructions. We conclude that the excitability in left premotor/motor right motor pathways is context-dependent and affects motor behaviour. Thus, the left premotor cortex is engaged not only in action selection but also in withholding and releasing a preselected movement generated by the right motor cortex.     

Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study.

Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements.     

Motor aspects of cue-related neuronal activity in premotor cortex of the rhesus monkey

Neurons in the premotor cortex of rhesus monkeys were studied under two conditions: (1) visuospatial cues were given to guide the amplitude, direction, and onset time of forearm movements or (2) physically identical visual cues were given when reward was contingent on withholding movement. Neurons with sustained activity following the cues were preferentially active when the cues triggered a movement. Thus, activity of certain neurons in this cortical field is linked to motor set, i.e. intention to make a movement in response to the cue, rather than the visual cue per se.     

Activity in the Precentral Motor Areas After Presentation of Targets for Delayed Reaching Movements Varies with the Initial Arm Position

We studied single unit activity in the primary motor and premotor cortex during preparation for unrestrained arm movements that the monkey made to a right or left visual target. 'Set-related' activity occurring during an instructed delay period could not only vary with the target location, but also with the initial arm posture which was changed via a motor-driven forearm support between two positions. Modulation with arm displacement of some cells was contingent upon prior instruction, i.e. it occurred only if a target for the upcoming movement was presented, and for the majority of neurons it was different from the effects caused by the same passive arm shift when being applied before the visual instruction cue. Furthermore, responses to presentation of the same target were found to depend on the starting position of the hand. These findings suggest that both kinaesthetic and visual information interact in motor cortical cells in an appropriate manner for elaborating the movement trajectory.     

Decreased corticospinal excitability after subthreshold 1 Hz rTMS over lateral premotor cortex

OBJECTIVE: To study whether trains of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) over premotor, prefrontal, or parietal cortex can produce changes in excitability of motor cortex that outlast the application of the train. BACKGROUND: Prolonged 1 Hz rTMS over the motor cortex can suppress the amplitude of motor-evoked potentials (MEP) for several minutes after the end of the train. Because TMS can produce effects not only at the site of stimulation but also at distant sites to which it projects, the authors asked whether prolonged stimulation of sites distant but connected to motor cortex can also lead to lasting changes in MEP. METHODS: Eight subjects received 1500 magnetic stimuli given at 1 Hz over the left lateral frontal cortex, the left lateral premotor cortex, the hand area of the left motor cortex, and the left anterior parietal cortex on four separate days. Stimulus intensity was set at 90% active motor threshold. Corticospinal excitability was probed by measuring the amplitude of MEP evoked in the right first dorsal interosseous muscle by single suprathreshold stimuli over the left motor hand area before, during, and after the conditioning trains. RESULTS: rTMS over the left premotor cortex suppressed the amplitude of MEP in the right first dorsal interosseous muscle. The effect was maximized (approximately 50% suppression) after 900 pulses and outlasted the full train of 1500 stimuli for at least 15 minutes. Conditioning rTMS over the other sites did not modify the size of MEP. A control experiment showed that left premotor cortex conditioning had no effect on MEP evoked in the left first dorsal interosseous muscle. CONCLUSIONS: Subthreshold 1 Hz rTMS of the left premotor cortex induces a short-lasting inhibition of corticospinal excitability in the hand area of the ipsilateral motor cortex. This may provide a model for studying the functional interaction between premotor and motor cortex in healthy subjects and patients with movement disorders.     

Neural substrates of resisting craving during cigarette cue exposure.

BACKGROUND: In cigarette smokers, the most commonly reported areas of brain activation during visual cigarette cue exposure are the prefrontal, anterior cingulate, and visual cortices. We sought to determine changes in brain activity in response to cigarette cues when smokers actively resist craving. METHODS: Forty-two tobacco-dependent smokers underwent functional magnetic resonance imaging, during which they were presented with videotaped cues. Three cue presentation conditions were tested: cigarette cues with subjects allowing themselves to crave (cigarette cue crave), cigarette cues with the instruction to resist craving (cigarette cue resist), and matched neutral cues. RESULTS: Activation was found in the cigarette cue resist (compared with the cigarette cue crave) condition in the left dorsal anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and precuneus. Lower magnetic resonance signal for the cigarette cue resist condition was found in the cuneus bilaterally, left lateral occipital gyrus, and right postcentral gyrus. These relative activations and deactivations were more robust when the cigarette cue resist condition was compared with the neutral cue condition. CONCLUSIONS: Suppressing craving during cigarette cue exposure involves activation of limbic (and related) brain regions and deactivation of primary sensory and motor cortices.     

Premotor cortex and the retrieval of movement

It is argued that the premotor cortex plays a crucial role in the retrieval of movement. Monkeys with bilateral lesions in premotor cortex were found to be impaired at selecting between two movements on the basis of visual cues. This was true whether the visual cue was present at the time of response or was no longer visible. Yet other monkeys with bilateral lesions in dorsal premotor cortex had little difficulty in remembering a movement if they had just been forced to make it a few seconds earlier. It is suggested that the premotor cortex is involved in the process of translation from a visual or auditory cue to an associated movement.     

The Primate Striatum: Neuronal Activity in Relation to Spatial Attention Versus Motor Preparation

The primate basal ganglia are known to be involved in the initiation and control of visually guided movements. However, the precise role of these structures is not clear, partly because most neurophysiological studies have not dissociated neuronal activity related to visuomotor processing from that reflecting other aspects of behaviour, such as shifts of spatial attention. Moreover, the way the basal ganglia function together with the frontal cortex during movement initiation and execution is still a matter of debate. In an effort to clarify these issues, we recorded single neurons from the striatum (caudate nucleus and putamen) in two rhesus monkeys trained to perform a conditional visuomotor task, and compared their properties with those of the frontal cortex. The experimental paradigm was designed to distinguish neuronal activity associated with shifts of attention from that reflecting motor preparation. In a given trial, an identical visual stimulus could serve as a cue for the reorientation of spatial attention or as a cue for establishing a motor set depending on when it occurred during that trial. Additional aspects of the paradigm were designed to identify neurons whose activity differed when various stimulus configurations instructed the same action (stimulus effect), as well as neurons whose activity differed when two different actions were instructed by the same stimulus (movement effect). The majority of cells (60%) were preferentially active after instructional cues, 38% discharged preferentially after attentional cues, and the remaining 2% of cells discharged equally after both types of cue. Neurons active after instructional cues were further analysed for stimulus and movement effects. During movement preparation, the activity of the vast majority of striatal cells (putamen, 81%; caudate, 76%) varied significantly when different stimuli instructed the same action. Likewise, when different movements were instructed by the same stimulus, preparatory activity of a majority of cells (putamen, 92%; caudate, 82%) changed. Consequently, a substantial proportion of cells showed combined stimulus and movement effects. Comparison of these neuronal properties with those of the dorsal premotor cortex showed significantly higher proportions of cells in the striatum whose activity reflected sensory or sensorimotor processing. These results suggest that the basal ganglia are involved in shifting attentional set and in high-order processes of movement initiation, including the linking of sensory information with behavioural responses.     

Uncovering a context-specific connectional fingerprint of human dorsal premotor cortex

Primate electrophysiological and lesion studies indicate a prominent role of the left dorsal premotor cortex (PMd) in action selection based on learned sensorimotor associations. Here we applied transcranial magnetic stimulation (TMS) to human left PMd at low or high intensity while right-handed individuals performed externally paced sequential key presses with their left hand. Movements were cued by abstract visual stimuli, and subjects either freely selected a key press or responded according to a prelearned visuomotor mapping rule. Continuous arterial spin labeling was interleaved with TMS to directly assess how stimulation of left PMd modulates task-related brain activity depending on the mode of movement selection. Relative to passive viewing, both tasks activated a frontoparietal motor network. Compared with low-intensity TMS, high-intensity TMS of left PMd was associated with an increase in activity in medial and right premotor areas without affecting task performance. Critically, this increase in task-related activity was only present when movement selection relied on arbitrary visuomotor associations but not during freely selected movements. Psychophysiological interaction analysis revealed a context-specific increase in functional coupling between the stimulated left PMd and remote right-hemispheric and mesial motor regions that was only present during arbitrary visuomotor mapping. Our TMS perturbation approach yielded causal evidence that the left PMd is implicated in mapping external cues onto the appropriate movement in humans. Furthermore, the data suggest that the left PMd may transiently form a functional network together with right-hemispheric and mesial motor regions to sustain visuomotor mapping performed with the left nondominant hand.     

The involvement of monkey premotor cortex neurones in preparation of visually cued arm movements

Some neurones in macaque postarcuate premotor area modulate their firing frequency in relation to motor tasks which require visual information. We previously reported that a large proportion of these neurones modulate during execution of a detour reaching task in which the movement phase was separated in time from the phase in which the monkey received a visual cue for the movement required to retrieve a food reward. A large proportion of task-related neurones (75%) modulated during this 'visual' phase, in which no task-related movements were made. This modulation was related to the position of the food reward, which served as the visual cue. Most of these neurones were located in cortical area 6, close to the arcuate curvature and its spur, but also more caudally in area 4 and rostrally in area 8. In the present chronic recording experiments in monkeys, several variations of the original task were used in order to test whether the 'visual'-related neuronal modulation could be involved in preparation of the upcoming movement. This modulation is unlikely to be related to any eye or arm movements occurring during the visual phase or to changes in environmental illumination. Neither can it be related to the presence of the visual cue in a particular part of the visual field, since the pattern of neuronal modulation was similar when a cue with a fixed position was used. This modulation was, however, contingent upon the occurrence of food retrieval during the subsequent 'movement phase', since it was abolished or diminished during presentation of a 'food-reward' which the monkey did not retrieve. For several neurones, modulation pattern during the visual phase depended on whether the food reward was to be retrieved with a gross hand movement or with relatively independent finger movements. It is likely, therefore, that neurones in the postarcuate premotor cortex are involved in preparation for arm movements with the help of visual cues. The results are discussed in view of corticocortical pathways which might be involved in transmission of visual information from visual areas through parietal association areas and premotor cortex to the primary motor cortex.     

Paired pulse TMS over the right posterior parietal cortex modulates visuospatial perception

OBJECTIVE: We previously observed a relative contralateral neglect by right parietal single-pulse TMS given 150 ms after visual stimulus presentation. Here we investigated the effects of parietal paired TMS in normal subjects performing a visuospatial task. METHODS: Thirteen right-handed healthy subjects underwent a line-length judgement task during single-pulse and paired (1, 3, 5, 10 ms ISIs) TMS, delivered on the right parietal cortex 150 ms after visual stimulus. RESULTS: Single pulse TMS over the right parietal cortex induced a significant rightward bias compared to the baseline condition. At 1 and 3 ms ISIs, paired-pulse TMS did not show any effect in comparison with single pulse TMS. More importantly, 5 ms ISI was able to restore baseline levels, thus inducing a significant improvement of the performance compared to single-pulse TMS and 1-3 ms ISIs. CONCLUSIONS: Paired TMS seems able to modulate activity of the right posterior parietal cortex in healthy subjects performing a cognitive visuospatial task.     

The essential role of Broca's area in imitation

The posterior sector of Broca's area (Brodmann area 44), a brain region critical for language, may have evolved from neurons active during observation and execution of manual movements. Imaging studies showing increased Broca's activity during execution, imagination, imitation and observation of hand movements support this hypothesis. Increased Broca's activity in motor task, however, may simply be due to inner speech. To test whether Broca's area is essential to imitation, we used repetitive transcranial magnetic stimulation (rTMS), which is known to transiently disrupt functions in stimulated areas. Subjects imitated finger key presses (imitation) or executed finger key presses in response to spatial cues (control task). While performing the tasks, subjects received rTMS over the left and right pars opercularis of the inferior frontal gyrus (where Brodmann area 44 is probabilistically located) and over the occipital cortex. There was significant impairment in imitation, but not in the control task, during rTMS over left and right pars opercularis compared to rTMS over the occipital cortex. This suggests that Broca's area is a premotor region essential to finger movement imitation.     

Locating the human frontal eye fields with transcranial magnetic stimulation

The variability in the location and function of the human frontal eye fields (FEFs) was assessed using transcranial magnetic stimulation (TMS). Ten subjects performed a saccadic eye movement task previously shown to be influenced by TMS of the FEFs. A sequence of points over the prefrontal cortex was stimulated until an effective site of the TMS was found that induced contralateral saccade delays. In 7 out of the 10 subjects, we were able to localize a region in the prefrontal cortex that when stimulated produced delays in the execution of contralateral saccadic eye movements. The location of this functionally defined FEF region across these subjects was approximately 1.5 cm anterior to the motor hand area, although there was considerable variability in this measure. In the remaining 3 subjects, no site within our circumscribed probing was found that when disrupted with TMS produced delays in contralateral saccadic eye movements. The inter-individual differences in the location and function of the FEFs highlights the importance of using functional as well as anatomical landmarks when attempting to localize brain structures.     

Ipsilateral involvement of primary motor cortex during motor imagery

To investigate whether motor imagery involves ipsilateral cortical regions, we studied haemodynamic changes in portions of the motor cortex of 14 right-handed volunteers during actual motor performance (MP) and kinesthetic motor imagery (MI) of simple sequences of unilateral left or right finger movements, using functional magnetic resonance imaging (fMRI). Increases in mean normalized fMRI signal intensities over values obtained during the control (visual imagery) task were found during both MP and MI in the posterior part of the precentral gyrus and supplementary motor area, both on the contralateral and ipsilateral hemispheres. In the left lateral premotor cortex, fMRI signals were increased during imagery of either left or right finger movements. Ipsilateral cortical clusters displaying fMRI signal changes during both MP and MI were identified by correlation analyses in 10 out of 14 subjects; their extent was larger in the left hemisphere. A larger cortical population involved during both contralateral MP and MI was found in all subjects. The overall spatial extent of both the contralateral and the ipsilateral MP + MI clusters was approximately 90% of the whole cortical volume activated during MP. These results suggest that overlapping neural networks in motor and premotor cortex of the contralateral and ipsilateral hemispheres are involved during imagery and execution of simple motor tasks.     

Dissociating effector and movement direction selection during the preparation of manual reaching movements: evidence from lateralized ERP components.

OBJECTIVE: The present study investigated whether lateralized ERP components triggered during covert manual response preparation (ADAN, LDAP) reflect effector selection, the selection of movement direction, or both. METHODS: Event-related brain potentials were recorded during a response precueing paradigm where visual cues provided either partial (Experiment 1) or full (Experiment 2) information about the response hand and the direction for a subsequent reaching movement. RESULTS: ADAN and LDAP components were elicited even when only partial response information was available, demonstrating that they do not require the presence of a fully specified motor program. The ADAN was elicited in a similar fashion regardless of whether effector or movement direction information was provided, suggesting that the underlying mechanisms are equally sensitive to both types of response-related information. In contrast, the LDAP was larger in response to cues providing effector information, but was also reliably present when movement direction was available. CONCLUSIONS: ADAN and LDAP components reflect preparatory activity within anterior and posterior parts of the parieto-premotor sensorimotor network where different parameters for manual reaching movements are programmed independently. SIGNIFICANCE: These results support the claim of the premotor theory of attention that shared sensorimotor control mechanisms are involved in attention and motor programming.     

The effect of rTMS over left and right dorsolateral premotor cortex on movement timing of either hand

It has been suggested that the left dorsolateral premotor cortex (dPMC) controls timing abilities of either hand. To further clarify its functional significance for movement timing, low-frequency repetitive transcranial magnetic stimulation (rTMS) was applied over the left and right dPMC, respectively, while subjects performed an auditorily paced finger-tapping task with each hand. rTMS over the left dPMC decreased tapping accuracy of both hands, whereas no behavioural effects occurred following right dPMC stimulation. To elucidate the time window in which left dPMC TMS disturbs synchronization abilities, pairs of TMS pulses were applied over the left dPMC and the left anterior parietal cortex serving as control condition. TMS pulses were applied randomly at 40 ms, 80 ms, 120 ms, 160 ms, 200 ms and 240 ms before pacer onset, as taps precede the pacing signal for about 20–60 ms. Again, the analysis revealed that TMS over the left dPMC disturbed synchronization abilities of either hand; however, this effect was shown at different times suggesting that the left dPMC affects the right M1 via at least one additional relay station. The present data support the hypothesis that the left dPMC is crucial for accurate timing of either hand. Additionally, they reveal a piece of evidence that the left dPMC affects the left hand not via a direct left dPMC–right M1 connection.     

The role of V5 (hMT+) in visually guided hand movements: an fMRI study

Electrophysiological studies in animals suggest that visuomotor control of forelimb and eye movements involves reciprocal connections between several areas (striate, extrastriate, parietal, motor and premotor) related to movement performance and visuospatial coding of movement direction. The extrastriate area MT [V5 (hMT+) in humans] located in the "dorsal pathway" of the primate brain is specialized in the processing of visual motion information. The aim of our study was to investigate the functional role of V5 (hMT+) in the control of visually guided hand movements and to identify the corresponding cortex activation implicated in the visuomotor tasks using functional magnetic resonance imaging. Eight human subjects performed visually guided hand movements, either continuously tracking a horizontally moving target or performing ballistic tracking movements of a cursor to an eccentric stationary target while fixating a central fixation cross. The tracking movements were back-projected onto the screen using a cursor which was moved by an MRI-compatible joystick. Both conditions activated area V5 (hMT+), right more than left, particularly during continuous tracking. In addition, a large-scale sensorimotor circuit which included sensorimotor cortex, premotor cortex, striatum, thalamus and cerebellum as well as a number of cortical areas along the intraparietal sulcus in both hemispheres were activated. Because activity was increased in V5 (hMT+) during continuous tracking but not during ballistic tracking as compared to motion perception, it has a pivotal role during the visual control of forelimb movements as well.     

Preparation of visually cued arm movements in monkey. Involvement of inferior parietal cortex

Single-unit activity was recorded in monkey inferior parietal lobule (IPL) during performance of a visually cued limb motor task. Many neurons in the IPL modulated their activity just after the visual cue was presented, similar to the neuronal activity observed in the premotor cortex in a previous experiment. It is suggested that IPL neurons are involved in preparation of visually cued limb movement. The present results are discussed in view of a possible role for IPL and premotor cortex in processing visual information for use by the primary motor area.     

Functional MR imaging and traumatic paraplegia: preliminary report

PURPOSE: To evaluate residual activity in the sensorimotor cortex of the lower limbs in paraplegia. METHODS: 5 patients suffering from a complete paralysis after traumatic medullar lesion (ASIA=A). Clinical evaluation of motility and sensitivity. 1. Control functional MR study of the sensorimotor cortex during simultaneous movements of hands, imaginary motor task and passive hands stimulation. 2. Concerning the lower limbs, 3 fMRI conditions: 1-patient attempts to move his toes with flexion-extension, 2-mental imagery task of the same movement, 3-peripheral passive proprio-somesthesic stimulation (squeezing) of the big toes. RESULTS: Activations were observed in the primary sensorimotor cortex (M1), premotor regions and in the supplementary motor area (SMA) during movement and mental imaginary tasks in the control study and during attempt to move and mental imaginary tasks in the study concerning the lower limbs. Passive somesthesic stimulation generated activation posterior to the central sulcus for 2 patients. CONCLUSION: Activations in the sensorimotor cortex of the lower limbs can be generated either by attempting to move or mental evocation. In spite of a clinical evaluation of complete paraplegia, fMRI can show a persistence of sensitive anatomic conduction, confirmed by Somesthesic Evoked Potentials.