Preoperative localization of hand motor cortex by adaptive spatial filtering of magnetoencephalography data

OBJECT: The goal of this study was to examine the sensitivity and specificity in preoperative localization of hand motor cortex by imaging regional event-related desynchronization (ERD) of brainwaves in the beta frequency band (15-25 Hz) involved in self-paced movement. METHODS: Using magnetoencephalography (MEG), the authors measured ERD that occurred before self-paced unilateral index finger flexion in 66 patients with brain tumors, epilepsy, and arteriovenous malformations. RESULTS: The authors applied an adaptive spatial filtering algorithm to MEG data and found that peaks of the tomographic distribution of beta-band ERD sources reliably localized hand motor cortex compared with electrical cortical stimulation. They also observed high specificity in estimating contralateral hand motor cortical representations relative to somatosensory cortex. Neither presence nor location of tumor changed the qualitative or quantitative location of motor cortex relative to somatosensory cortex. CONCLUSIONS: An imaging protocol using ERD obtained by adaptive spatial filtering of MEG data can be used for extremely reliable preoperative localization of hand motor cortex.     

Activity-dependent modulation of synaptic transmission in the intact human motor cortex revealed with transcranial magnetic stimulation

Activity-dependent modulation of cortical synaptic transmission is a fundamental mechanism involved in learning and memory storage. This modulation has been widely studied in in vitro brain slices and in vivo animal models. More recently, transcranial magnetic stimulation has allowed detection of activity-dependent excitability modulation occurring in the intact human primary motor cortex (MI) after execution of different kinds of motor tasks. Both increased and decreased MI excitability have been described after exercise. While increased MI excitability is generally considered direct expression of cortical synaptic plasticity, a controversy still exists as to whether decreased MI excitability reflects fatigue of central nervous system (CNS) structures or cortical neuronal reorganization taking place after exercise. Here, we extend previous findings in order to provide further support for the latter hypothesis. Abduction- adduction movements of the thumb performed for 1 min at 2 Hz frequency rate produce a 55% decrease in MI excitability of mean 30 min duration. Similar decrements in amplitude and duration of motor evoked potentials (MEPs) are not reached if the same task is performed once again during the maximal inhibition phase (10 min post-exercise) produced by a previous activation. Moreover, the same task performed at a lower (1 Hz) frequency rate produces no significant MEP changes but can transiently reverse activity-dependent depression obtained after previous 2 Hz movements. Repeated execution of the same task (2 Hz), each being performed after recovery from a previously induced MEP depression, ceases to produce an MEP decrement, suggesting adaptation in MI excitability modulation. This adaptation is long lasting and task-specific, since a different motor task (1 min circular movement of the thumb) restores activity-dependent modulation. Overall, these findings suggest that the dynamic modulation of MEPs occurring after execution of different kinds of simple motor skills reflects some form of activity-dependent, plastic neuronal reorganization instead of CNS fatigue. Possible anatomo-functional mechanisms involved in this activity-dependent modulation of MI excitability are discussed.     

The role of parietal cortex in awareness of self-generated movements: a transcranial magnetic stimulation study

Awareness of self-generated movements arises from comparing motor plans, and the accompanying (hypothetical) efference copy, with the visual and proprioceptive consequences of movement. Here we used repetitive transcranial magnetic stimulation (rTMS) to investigate the role of a posterior region in the superior parietal lobule (SPL) in this process. Nine healthy volunteers performed a finger extension actively and passively while wearing a CyberGlove; the glove recorded these (actual) finger movements and used this information in real time to move a virtual hand displayed on a computer screen. To assess the participant's awareness of movement onset, we introduced a delay between the onset of the actual and virtual movement (60-270 ms, 30 ms increments); the task was to judge whether the virtual hand movements were delayed relative to the actual hand movements. Low-frequency rTMS (15 min, 0.6 Hz) was applied either over the left SPL or the left temporal cortex (control site) to decrease excitability of these regions and, in turn, test their role in the awareness of self-generated movement. Following the SPL stimulation, participants' assessments of asynchrony were impaired for active but not passive movements. No significant changes were observed after rTMS applied over the control site. We suggest that these findings are consistent with the role of the SPL in evaluating the temporal congruency of peripheral (visual) and central (efference copy) signals associated with self-generated movements. As such, this region may contribute to the sense of 'agency' and its disturbances in disorders such as apraxia and schizophrenia.     

Priming frequencies of transcranial magnetic stimulation over Wernicke's area modulate word detection

Priming stimulations have shown powerful effects on motor cortex behavior. However, the effects over language areas have not been explored. We assessed the effects of different priming frequencies of repetitive transcranial magnetic stimulation (rTMS), 1 Hz rTMS or 50 Hz bursts of rTMS (theta burst stimulation [TBS]), on temporoparietal language areas (i.e., Wernicke's area) localized with functional magnetic resonance imaging. Functional maps were acquired during an auditory word-detection task with native or foreign language sentences in 14 healthy men. Frameless stereotaxy was used to guide the transcranial magnetic stimulation coil position over Wernicke's area. Active and placebo randomized sessions of priming stimulations (1 Hz rTMS or TBS) were applied at rest, and response times (RTs) were recorded during the auditory word-detection task performed subsequently with 1 Hz rTMS. Individual anatomofunctional maps localized activation in Wernicke's area. Repeated-measure analysis of variance for RTs revealed that priming with 1 Hz rTMS facilitated the detection of native words, whereas priming with TBS facilitated the detection of foreign words. Consistent with motor cortex studies, these findings suggest that priming frequency plays a crucial role in word detection in the auditory stream.     

Motor control in basal ganglia circuits using fMRI and brain atlas approaches

In this study, we examined how the motor, premotor and associative basal ganglia territories process movement parameters such as the complexity and the frequency of movement. Twelve right-handed volunteers were studied using EPI BOLD contrast (3 T) while performing audio-paced finger tapping tasks designed to differentiate basal ganglia territories. Tasks varied movement complexity (repetitive index tapping, simple sequence of finger movements and complex sequence of 10 moves) and frequency (from 0.5 to 3 Hz). Activation maps were coregistered onto a 3-D brain atlas derived from post-mortem brains. Three main patterns of activation were observed. In the posterior putamen and the sensorimotor cortex, signal increased with movement frequency but not with movement complexity. In premotor areas, the anterior putamen and the ventral posterolateral thalamus, signal increased regularly with increasing movement frequency and complexity. In rostral frontal areas, the caudate nucleus, the subthalamic nucleus and the ventral anterior/ventrolateral thalamus, signal increased mainly during the complex task and the high frequency task (3 Hz). These data show the different roles of motor, premotor and associative basal ganglia circuits in the processing of motor-related operations and suggest that activation can be precisely located within the entire circuitry of the basal ganglia.     

Abnormal motor preparation in severe traumatic brain injury with good recovery

Movement-related cortical potentials (MRCPs) were examined in seven patients with severe traumatic brain injury (TBI) and 12 matched control subjects. All patients had clinically established good recovery by the time of testing. Flexion movements of the index finger of the left or right hand were recorded in two (alternating and repetitive) self-paced conditions and in one externally triggered condition. In control subjects, the bereitschaftspotential (BP) component of MRCP was detected approximately 2000 msec prior to movement onset in the self-paced conditions and was larger and earlier in the alternating compared to the repetitive condition. The BP component was absent in the externally triggered condition. In TBI patients, the BP was greatly reduced and no difference between the alternating-repetitive conditions was detected; in contrast, only small differences were present in the controls for the negative slope (NS) and MP components and no difference for the reafferent positivity (RAP) component. A dipole analysis indicated the supplementary motor area and the premotor area as the likely generators of BP and NS' components, respectively. Gradientrecalled echo magnetic resonance imaging allowed the detection of a number of small hypointense lesions primarily located in the frontal lobes, as in diffuse axonal injury. This pattern of results indicates a selective deficit in motor preparation and a relatively spared pattern of activation during and following movement in these patients. Imaging data appear generally consistent with the pattern of MRCPs observed in the patient group. Implications of these results for the problem of slowness in TBI patients are discussed.     

Repeatedly pairing vagus nerve stimulation with a movement reorganizes primary motor cortex

Although sensory and motor systems support different functions, both systems exhibit experience-dependent cortical plasticity under similar conditions. If mechanisms regulating cortical plasticity are common to sensory and motor cortices, then methods generating plasticity in sensory cortex should be effective in motor cortex. Repeatedly pairing a tone with a brief period of vagus nerve stimulation (VNS) increases the proportion of primary auditory cortex responding to the paired tone (Engineer ND, Riley JR, Seale JD, Vrana WA, Shetake J, Sudanagunta SP, Borland MS, Kilgard MP. 2011. Reversing pathological neural activity using targeted plasticity. Nature. 470:101-104). In this study, we predicted that repeatedly pairing VNS with a specific movement would result in an increased representation of that movement in primary motor cortex. To test this hypothesis, we paired VNS with movements of the distal or proximal forelimb in 2 groups of rats. After 5 days of VNS movement pairing, intracranial microstimulation was used to quantify the organization of primary motor cortex. Larger cortical areas were associated with movements paired with VNS. Rats receiving identical motor training without VNS pairing did not exhibit motor cortex map plasticity. These results suggest that pairing VNS with specific events may act as a general method for increasing cortical representations of those events. VNS movement pairing could provide a new approach for treating disorders associated with abnormal movement representations.     

The influence of hand posture on corticospinal excitability during motor imagery: a transcranial magnetic stimulation study

In order to study the interaction between proprioceptive information and motor imagery, we herein investigate how compatible and incompatible postural signals influence corticospinal excitability during the mental simulation of hand movements. Subjects were asked to imagine themselves joining the tips of the thumb and the little finger while they maintained one of the two following hand postures: posture A (PA, compatible), little finger, index and thumb extended, the remaining fingers flexed; or posture B (PB, incompatible), index and thumb extended, other fingers flexed. All subjects rated the imagined finger opposition movements as easier to perform when the hand was kept in PA than in PB (P < 0.01) and the correlation between the duration of motor imagery and movement execution was also higher for PA than PB (P < 0.01). For each posture, motor evoked potentials (MEPs) elicited by focal transcranial magnetic stimulation (TMS) of the left motor cortex were recorded from the right opponens pollicis muscle during both motor imagery (MI) and rest (R) conditions. MEP area varied according to the hand posture: PA induced a higher increase in corticospinal excitability, when compared with PB. These results indicate that the actual limb posture affects the process of motor imagery. The source of this postural modulation effect is discussed.     

Enhanced cortical activation in the contralesional hemisphere of chronic stroke patients in response to motor skill challenge

The brain processes involved in the restoration of motor skill after hemiparetic stroke are not fully understood. The current study compared cortical activity in chronic stroke patients who successfully recovered hand motor skill and normal control subjects during performance of kinematically matched unskilled and skilled hand movements using functional magnetic resonance imaging. We found that cortical activation during performance of the unskilled movement was increased in the patients relative to controls in the contralesional primary sensorimotor cortex. Performance of the skilled movement elicited increased activation in the patients relative to controls in the contralesional primary sensorimotor cortex, ventral premotor cortex, supplementary motor area/cingulate, and occipitoparietal cortex. Further, the activation change in the contralesional occipitoparietal cortex was greater in the patients relative to controls with the increase in motor skill challenge. Kinematic differences, mirror movements, and residual motor deficits did not account for the enhanced activation in the contralesional cortices in the patients. These results suggest that activation in the contralesional cortical network was enhanced as a function of motor skill challenge in stroke patients with good motor recovery. The findings of the current study suggest that successful recovery of motor skill after hemiparetic stroke involves participation of the contralesional cortical network.     

Motor cortex dynamics in visuomotor production of speech and non-speech mouth movements

We investigated timing and hemispheric balance of motor cortex activation when kinetically similar speech and non-speech mouth movements and sequences of such movements were triggered by visually presented letter- and symbol-strings. As an index of motor cortex activation, we used magnetoencephalographic recording of task-related change of precentral 20 Hz (16-24 Hz) activity. Suppression of the 20 Hz rhythm revealed pre-movement activation in the face representation areas that was tied to visual instruction, not movement onset. The 20 Hz rhythm remained suppressed throughout the preparation and execution of mouth movements and was followed by post-movement rebound. Left hemisphere preceded the right at the onset and offset of the suppression, similarly for isolated and sequential speech and non-speech movements. Pattern of task-related change in 20 Hz activity was otherwise symmetrical. In the face areas, the overall modulation of 20 Hz activity increased with sequence length and motor demands. Hand representation areas showed also weak reactivity, with systematically larger modulation of 20 Hz activity for non-speech than speech movements. Our results suggest an active role for the motor cortex in cognitive control of visually triggered mouth movements, not limited to movement execution.     

Long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic tinnitus.

OBJECTIVES: The pathophysiologic mechanisms of idiopathic tinnitus remain unclear. Recent studies demonstrated focal brain activation in the auditory cortex of patients with chronic tinnitus. Low-frequency repetitive transcranial magnetic stimulation (rTMS) is able to reduce cortical hyperexcitability. STUDY DESIGN: Fusing of the individual PET-scan with the structural MRI-scan (T1, MPRAGE) allowed us to identify exactly the area of increased metabolic activity in the auditory cortex of patients with chronic tinnitus. With the use of a neuronavigational system, this target area was exactly stimulated by the figure 8-shaped magnetic coil. In a prospective study, rTMS (110% motor threshold; 1 Hz; 2000 stimuli/day over 5 days) was performed using a placebo controlled cross-over design. Patients were blinded regarding the stimulus condition. For the sham stimulation a specific sham-coil system was used. Fourteen patients were followed for 6 months. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller). SETTING: Tertiary referral medical center. RESULTS: Increased metabolic activation in the auditory cortex was verified in all patients. After 5 days of verum rTMS, a highly significant improvement of the tinnitus score was found whereas the sham treatment did not show any significant changes. The treatment outcome after 6 months still demonstrated significant reduction of tinnitus score. CONCLUSION: These preliminary results demonstrate that neuronavigated rTMS offers new possibilities in the understanding and treatment of chronic tinnitus.     

Rapid cortical oscillations and early motor activity in premature human neonate

Delta-brush is the dominant pattern of rapid oscillatory activity (8-25 Hz) in the human cortex during the third trimester of gestation. Here, we studied the relationship between delta-brushes in the somatosensory cortex and spontaneous movements of premature human neonates of 29-31 weeks postconceptional age using a combination of scalp electroencephalography and monitoring of motor activity. We found that sporadic hand and foot movements heralded the appearance of delta-brushes in the corresponding areas of the cortex (lateral and medial regions of the contralateral central cortex, respectively). Direct hand and foot stimulation also reliably evoked delta-brushes in the same areas. These results suggest that sensory feedback from spontaneous fetal movements triggers delta-brush oscillations in the central cortex in a somatotopic manner. We propose that in the human fetus in utero, before the brain starts to receive elaborated sensory input from the external world, spontaneous fetal movements provide sensory stimulation and drive delta-brush oscillations in the developing somatosensory cortex contributing to the formation of cortical body maps.     

Suppressing versus releasing a habit: frequency-dependent effects of prefrontal transcranial magnetic stimulation

When subjects are required to generate a random sequence of numbers they typically produce too many forward and backward 'counts' (e.g. 5-6, 4-3). This counting bias is interpreted as the consequence of an interference by overlearned tendencies to arrange numbers according to their natural order. Inhibition of such well-learned routines is known to rely on frontal lobe functioning. We examined differential effects of slow (1 Hz) and fast (10 Hz) repetitive transcranial magnetic stimulation (rTMS) over the left or right dorsolateral prefrontal cortex (DLPFC) on random number generation (RNG) performance. Eighteen healthy men performed an RNG task. Those subjects stimulated over the left DLPFC showed a frequency-dependent rTMS effect: counting bias was significantly reduced after the 1 Hz stimulation compared with baseline, but significantly exaggerated after the 10 Hz stimulation compared with 1 Hz stimulation. In contrast, the sequences of the subjects stimulated over the right DLPFC showed the well-known excess of counting in all conditions (i.e. baseline, 1 Hz and 10 Hz). These findings confirm the functional importance of specifically the left DLPFC in sequential response production and show, for the first time, that rTMS affects cognitive processing in a frequency-dependent manner.     

What disconnection tells about motor imagery: evidence from paraplegic patients

Brain activation during motor imagery has been the subject of a large number of studies in healthy subjects, leading to divergent interpretations with respect to the role of descending pathways and kinesthetic feedback on the mental rehearsal of movements. We investigated patients with complete spinal cord injury (SCI) to find out how the complete disruption of motor efferents and sensory afferents influences brain activation during motor imagery of the disconnected feet. Eight SCI patients underwent behavioral assessment and functional magnetic resonance imaging. When compared to a healthy population, stronger activity was detected in primary and all non-primary motor cortical areas and subcortical regions. In paraplegic patients the primary motor cortex was consistently activated, even to the same degree as during movement execution in the controls. Motor imagery in SCI patients activated in parallel both the motor execution and motor imagery networks of healthy subjects. In paraplegics the extent of activation in the primary motor cortex and in mesial non-primary motor areas was significantly correlated with the vividness of movement imagery, as assessed by an interview. The present findings provide new insights on the neuroanatomy of motor imagery and the possible role of kinesthetic feedback in the suppression of cortical motor output required during covert movements.     

Whole-hand sensorimotor area: cortical stimulation localization and correlation with functional magnetic resonance imaging

OBJECT: The pli de passage moyen (PPM) is an omega-shaped cortical landmark bulging into the central sulcus. There has been considerable interest in the PPM given that hand motor and sensory tasks have been found on functional magnetic resonance (fMR) imaging to activate the structure. Note, however, that the cortical function subserved by the PPM is not completely understood. Finger and thumb function are somatotopically organized over the central area and encompass a larger cortical surface than the anatomical PPM. Therefore, a sensory or motor hand area within the PPM would be redundant with the somatotopically organized digit function in the primary sensorimotor cortex. In this study the authors aimed to clarify the function subserved by the PPM and further evaluate hand area function in the primary sensorimotor cortex. METHODS: To further elucidate the function subserved by the PPM, patients underwent cortical stimulation in the region of the PPM as well as fMR imaging-demonstrated activation of the hand area. Two separate analytical methods were used to correlate hand area functional imaging with whole-hand sensory and motor responses induced by cortical stimulation. RESULTS: A relationship of the anatomical PPM with cortical stimulation responses as well as hand fMR imaging activation was observed. CONCLUSIONS: A strong relationship was identified between the PPM, whole-hand sensory and motor stimulation responses, and fMR imaging hand activation. Whole-hand motor and whole-hand sensory cortical regions were identified in the primary sensorimotor cortex. It was localized to the PPM and exists in addition to the somatotopically organized finger and thumb sensory and motor areas.     

Comparison Between Monopolar and Bipolar Electrical Stimulation of the Motor Cortex

Intra-operative neurophysiological techniques allow reliable identification of the sensorimotor region and make their anatomical and functional preservation feasible. Monopolar cortical stimulation has recently been described as a new mapping technique. In the present study this method was compared to the "traditional" technique of bipolar stimulation. Functional mapping of the motor cortex was performed in 35 patients during surgery in the central region. The central sulcus (CS) was identified by somatosensory evoked potential (SEP) phase reversal. Cortical motor mapping was first performed by monopolar anodal stimulation with a train of 500 Hz (7-10 pulses) followed by bipolar stimulation (pulses at 60 Hz with max. 4 sec train duration). Surgery was performed under general anaesthesia without muscle relaxants. Of 280 motor responses elicited by bipolar cortical stimulation, 54.23% [152] were located in the primary motor cortex (PMC), 37.85% 106[ outside the motor strip in the secondary motor cortex (SMC), and 8% 22[ posterior to the CS. Of 175 motor responses elicited by monopolar cortical stimulation. 68.57% 120[ were located in the SMC, 23.42% 41[ in the SMC and 8% 14[ posterior to the CS. Contrary to the general clinical view, there is considerable overlapping of primary motor units over a cortical area much broader than the "classical" narrow motor strip along the CS. Bipolar cortical stimulation is more sensitive than monopolar for mapping motor function in the premotor frontal cortex. Both methods are equally sensitive for mapping the primary motor cortex.     

Alteration of cortical but not spinal inhibitory circuits in idiopathic scoliosis

Background: The pathogenesis of adolescent idiopathic scoliosis (AIS), including the role of brain and spinal inhibitory circuits, is still poorly elucidated. The aim of this study was to identify which central inhibitory mechanisms are involved in the pathogenesis of AIS.Design: A prospective neurophysiological study, using a battery of neurophysiological tests, such as cutaneous (CuSP) and cortical (CoSP) silent periods, motor evoked potentials (MEP) and paired-pulse transcranial magnetic stimulation (ppTMS).Settings: Neurophysiological laboratory.Participants: Sixteen patients with AIS (14 females, median age 14.4) and healthy controls.Outcome measures: MEPs were obtained after transcranial magnetic stimulation (TMS) and recorded from the abductor pollicis muscle (APB). ppTMS was obtained at interval ratios (ISI) of 1, 2, 3, 6, 10, 15 and 20 ms. The cortical silent period (CoSP) was recorded from the APB. The cutaneous silent period (CuSP) was measured after painful stimuli delivered to the thumb while the subjects maintained voluntary contraction of the intrinsic hand muscles. The data were analyzed and compared with those from healthy subjects.Results: The CoSP duration was significantly prolonged in AIS patients. A significantly higher amplitude of ppTMS for ISI was found in all AIS patients, without remarkable left-right side differences. No significant difference in MEP latency or amplitude nor in the CuSP duration was obtained.Conclusion: Our observation demonstrates evidence of central nervous system involvement in adolescent idiopathic scoliosis (AIS). Lower intracortical inhibition, higher motor cortex excitability, and preserved spinal inhibitory circuits are the main findings of this study. A possible explanation of these changes could be attributed to impaired sensorimotor integration predominantly at the cortical level.     

Memory formation in the motor cortex ipsilateral to a training hand

Cortical reorganization within the primary motor cortex (M1) contralateral to a practicing hand has been extensively investigated. The extent to which the ipsilateral M1 participates in these plastic changes is not known. Here, we evaluated the influence of unilateral hand practice on the organization of the M1 ipsilateral and contralateral to the practicing hand in healthy human subjects. Index finger movements elicited by single-pulse transcranial magnetic stimulation (TMS) delivered to each M1 were evaluated before and after practice of unilateral voluntary index finger abduction motions. Practice increased the proportion and acceleration of TMS-evoked movements in the trained direction and the amplitude of motor-evoked potentials (MEPs) in the abduction agonist first dorsal interosseous (FDI) muscle in the practicing hand and decreased the proportion and acceleration of TMS-evoked abduction movements and MEP amplitudes in the abduction agonist FDI in the opposite resting hand. Our findings indicate that unilateral hand practice specifically weakened the representation of the practiced movement in the ipsilateral M1 to an extent proportional to the strengthening effect in the contralateral M1, a result that varied with the practicing hand's position. These results suggest a more prominent involvement of interacting bilateral motor networks in motor memory formation and probably acquisition of unimanual motor skills than previously thought.     

A cortico-subcortical model for generation of spatially accurate sequential saccades.

This article provides a systems framework for the analysis of cortical and subcortical interactions in the control of saccadic eye movements, A major thesis of this model is that a topography of saccade direction and amplitude is preserved through multiple projections between brain regions until they are finally transformed into a temporal pattern of activity that drives the eyes to the target. The control of voluntary saccades to visual and remembered targets is modeled in terms of interactions between posterior parietal cortex, frontal eye fields, the basal ganglia (caudate and substantia nigra), superior colliculus, mediodorsal thalamus, and the saccade generator of the brainstem. Interactions include the modulation of eye movement motor error maps by topographic inhibitory projections, dynamic remapping of spatial target representations in saccade motor error maps, and sustained neural activity that embodies spatial memory. Models of these mechanisms implemented in our Neural Simulation Language simulate behavior and neural activity described in the literature, and suggest new experiments.     

The representation of blinking movement in cingulate motor areas: a functional magnetic resonance imaging study

Recent anatomical evidence from nonhuman primates indicates that cingulate motor areas (CMAs) play a substantial role in the cortical control of upper facial movement. Using event-related functional magnetic resonance imaging in 10 healthy subjects, we examined brain activity associated with volitional eye closure involving primarily the bilateral orbicularis oculi. The findings were compared with those from bimanual tapping, which should identify medial frontal areas nonsomatotopically or somatotopically related to bilateral movements. In a group-level analysis, the blinking task was associated with rostral cingulate activity more strongly than the bimanual tapping task. By contrast, the bimanual task activated the caudal cingulate zone plus supplementary motor areas. An individual-level analysis indicated that 2 foci of blinking-specific activity were situated in the cingulate or paracingulate sulcus: one close to the genu of the corpus callosum (anterior part of rostral cingulate zone) and the posterior part of rostral cingulate zone. The present data support the notion that direct cortical innervation of the facial subnuclei from the CMAs might control upper face movement in humans, as previously implied in nonhuman primates. The CMAs may contribute to the sparing of upper facial muscles after a stroke involving the lateral precentral motor regions.