Supplementary Motor Area Lesions Research Articles

Mapping of the supplementary motor area using repetitive navigated transcranial magnetic stimulation.

The supplementary motor area (SMA) is important for motor and language function. Damage to the SMA may harm these functions, yet tools for a preoperative assessment of the area are still sparse. The aim of this study was to validate a mapping protocol using repetitive navigated transcranial magnetic stimulation (rnTMS) and extend this protocol for both hemispheres and lower extremities. To this purpose, the SMA of both hemispheres were mapped based on a finger tapping task for 30 healthy subjects (35.97 ± 15.11, range 21-67 years; 14 females) using rnTMS at 20 Hz (120% resting motor threshold (RMT)) while controlling for primary motor cortex activation. Points with induced errors were marked on the corresponding MRI. Next, on the identified SMA hotspot a bimanual finger tapping task and the Nine-Hole Peg Test (NHPT) were performed. Further, the lower extremity was mapped at 20 Hz (140%RMT) using a toe tapping task. Mean finger tapping scores decreased significantly during stimulation (25.70taps) compared to baseline (30.48; p < 0.01). Bimanual finger tapping led to a significant increase in taps during stimulation (28.43taps) compared to unimanual tapping (p < 0.01). Compared to baseline, completion time for the NHPT increased significantly during stimulation (baseline: 13.6 s, stimulation: 16.4 s; p < 0.01). No differences between hemispheres were observed. The current study validated and extended a rnTMS based protocol for the mapping of the SMA regarding motor function of upper and lower extremity. This protocol could be beneficial to better understand functional SMA organisation and improve preoperative planning in patients with SMA lesions.

Perturbation of Macaque Supplementary Motor Area Produces Context-Independent Changes in the Probability of Movement Initiation

The contribution of the supplementary motor area (SMA) to movement initiation remains unclear. SMA exhibits premovement activity across a variety of contexts, including externally cued and self-initiated movements. Yet SMA lesions impair initiation primarily for self-initiated movements. Does SMA influence initiation across contexts or does it play a more specialized role, perhaps contributing only when initiation is less dependent on external cues? To address this question, we perturbed SMA activity via microstimulation at variable times before movement onset. Experiments used two adult male rhesus monkeys trained on a reaching task. We used three contexts that differed regarding how tightly movement initiation was linked to external cues. Movement kinematics were not altered by microstimulation. Instead, microstimulation induced a variety of changes in the timing of movement initiation, with different effects dominating for different contexts. Despite their diversity, these changes could be explained by a simple model where microstimulation has a stereotyped impact on the probability of initiation. Surprisingly, a unified model accounted for effects across all three contexts, regardless of whether initiation was determined more by external cues versus internal considerations. All effects were present for stimulation both contralateral and ipsilateral to the moving arm. Thus, the probability of initiating a pending movement is altered by perturbation of SMA activity. However, changes in initiation probability are independent of the balance of internal and external factors that establish the baseline initiation probability.SIGNIFICANCE STATEMENT The role of the supplementary motor area (SMA) in initiating movement remains unclear. Lesion experiments suggest that SMA makes a critical contribution only for self-initiated movements. Yet SMA is active before movements made under a range of contexts, suggesting a less-specialized role in movement initiation. Here, we use microstimulation to probe the role of SMA across a range of behavioral contexts that vary in the degree to which movement onset is influenced by external cues. We demonstrate that microstimulation produces a temporally stereotyped change in the probability of initiation that is independent of context. These results argue that SMA participates in the computations that lead to movement initiation and does so across a variety of contexts.

Working Memory Deficits After Lesions Involving the Supplementary Motor Area.

The Supplementary Motor Area (SMA)—located in the superior and medial aspects of the superior frontal gyrus—is a preferential site of certain brain tumors and arteriovenous malformations, which often provoke the so-called SMA syndrome. The bulk of the literature studying this syndrome has focused on two of its most apparent symptoms: contralateral motor and speech deficits. Surprisingly, little attention has been given to working memory (WM) even though neuroimaging studies have implicated the SMA in this cognitive process. Given its relevance for higher-order functions, our main goal was to examine whether WM is compromised in SMA lesions. We also asked whether WM deficits might be reducible to processing speed (PS) difficulties. Given the connectivity of the SMA with prefrontal regions related to executive control (EC), as a secondary goal we examined whether SMA lesions also hampered EC. To this end, we tested 12 patients with lesions involving the left (i.e., the dominant) SMA. We also tested 12 healthy controls matched with patients for socio-demographic variables. To ensure that the results of this study can be easily transferred and implemented in clinical practice, we used widely-known clinical neuropsychological tests: WM and PS were measured with their respective Wechsler Adult Intelligence Scale indexes, and EC was tested with phonemic and semantic verbal fluency tasks. Non-parametric statistical methods revealed that patients showed deficits in the executive component of WM: they were able to sustain information temporarily but not to mentally manipulate this information. Such WM deficits were not subject to patients' marginal PS impairment. Patients also showed reduced phonemic fluency, which disappeared after controlling for the influence of WM. This observation suggests that SMA damage does not seem to affect cognitive processes engaged by verbal fluency other than WM. In conclusion, WM impairment needs to be considered as part of the SMA syndrome. These findings represent the first evidence about the cognitive consequences (other than language) of damage to the SMA. Further research is needed to establish a more specific profile of WM impairment in SMA patients and determine the consequences of SMA damage for other cognitive functions.

Pre-operative fMRI localization of the supplementary motor area and its relationship with postoperative speech deficits.

Neurosurgery of the supplementary motor area (SMA) is associated with transient speech defects. We investigated whether SMA laterality correlates with postoperative speech defects. The authors reviewed 17 patients with SMA-area lesion resection and preoperative language fMRI. SMA laterality was calculated by comparison of voxel activation in paired SMAs by hand-drawn regions of interest (ROIs) (drawn by a neuroradiologist), and compared with qualitative assessment by two neuroradiologists. Postoperative speech defects before and after surgery were assessed by chart review. Six patients developed new speech defects that resolved within several months. Two of the patients had a pre-existing speech defect that had developed after prior SMA-area surgery. All these patients had left-sided lesions, while none of the four patients with a right-sided lesion developed a speech defect. Neuroradiologists' assessment of SMA laterality agreed with ROI calculation for the SMAs that were lateralized. However, for the SMAs in the "codominant" range by ROI, the neuroradiologists felt that all but one of the cases clearly lateralized, with the exception deemed indeterminate or codominant. No correlation between laterality of SMA and speech defect was identified. Twelve patients showed lateralization contralateral to the lesion. fMRI lateralization does not correlate with transient speech defects that developed from SMA-area surgery. Qualitative/visual assessment of SMA laterality was superior to ROI calculation because of the close proximity and possible overlap of signal from midline SMA. A majority of patients showed SMA lateralization contralateral to the SMA lesion.

Supplementary Motor Area Syndrome and Flexor Synergy of the Lower Extremities

Clinical presentation of supplementary motor area (SMA) syndrome includes complete akinesia of the contralateral side of the body and mutism, with secondary recovery of neurologic deficit. Multi-joint coordination is frequently impaired following the development of a brain lesion and is generally restricted by abnormal patterns of muscle activation within the hemiparetic limb, clinically termed muscle synergies. However, no work to date has confirmed this observation with the aid of objective methods, such as gait analysis, and the development of reflex pattern has not been suggested as a possible cause. We describe two unusual cases of flexor synergy after tumor resection of SMA lesions.

Support of the concept of interhemispheric rivalry by two consecutive strokes occurring in both hemispheres: a case study

Several lines of evidence indicate that the motor systems of both hemispheres are interconnected and influence each other. Unilateral pinch grips with very low force reduce the motor cortical excitability of a contralateral hand muscle [1]. Magnetic stimulation over both hemispheres with an appropriate interstimulus interval demonstrated the presence of an interhemispheric inhibition [2]. The concept of interhemispheric rivalry suggests that, after a stroke, the non-lesioned hemisphere could exert an inhibitory influence on the affected hemisphere [3] and that this dysbalance could impair restitution of functions. Here, we report the case of a patient who had developed a right-sided hemiparesis due to left-hemispheric intracerebral hemorrhage. This hemiparesis rapidly improved after suffering a right-hemispheric ischemic stroke. The 78-year-old right-handed gentleman suffered a spontaneous hemorrhage mainly affecting the left supplementary motor area (SMA) (Fig. 1a) while being treated with acetyl salicylic acid due to coronary heart disease. Three weeks after the incident, he presented with a rightsided hemiparesis that had persisted almost unchanged over time. Degrees of strength (Medical Research Council Scale) were between 3 and 4 for movements of the right upper limb. However, the patient did not use the arm spontaneously and seemed to be unable to generate voluntary movements if not forced to do so. He denied any sensory deficits for the right side. There was no clinical indication of spatial neglect. Somatosensory evoked potentials induced by median nerve stimulation had normal latencies and amplitudes. Motor potentials after transcranial magnetic stimulation were recorded from the first dorsal interosseous muscle and showed normal latencies and amplitudes for both sides. Twenty-four days after the hemorrhage, the patient developed a sudden spatial neglect to his left side. A magnetic resonance imaging of the brain showed an acute ischemic stroke mainly affecting the parietal cortex in the right hemisphere (Fig. 1b). Within the subsequent 3 days, the right-sided neurological symptoms disappeared almost completely. He started to employ his right upper extremity for activities of daily living. Clinical examination showed nothing but a slightly impaired dexterity. The left-sided spatial neglect resolved within 8 days after the ischemic stroke. In our opinion, the initial disuse of the right arm can be explained by the SMA lesion since the SMA is known to be relevant for generation of volitional movements [4]. We assume that, prior to the second stroke, the right parietal cortex exerted an inhibition on the left parietal cortex, similar to what has been described in neglect patients [5]. Using transcranial magnetic stimulation in healthy subjects, it has also been shown that the right (but not left) human posterior parietal cortex exerts a strong inhibitory activity over the contralateral homologous area [6]. After the ischemic lesion, this inhibition was reduced, allowing a parieto-frontal network in the left hemisphere to be activated and to compensate for the disturbed function of the SMA. Due to the rapid improvement after 3 weeks of symptom persistence, our observation cannot be explained by spontaneous recovery. Moreover, MRI at the time of the ischemic stroke showed an almost unchanged size of the hemorrhage. R. Sauerbrei J. Liepert (&) Department of Neurorehabilitation, Kliniken Schmieder, Bereich Neurorehabilitation, Zum Tafelholz 8, 78476 Allensbach, Germany e-mail: j.liepert@kliniken-schmieder.de

Clinical and MRI patterns of pericallosal artery infarctions: the significance of supplementary motor area lesions

Cerebral infarctions in the anterior cerebral artery (ACA) territory account for only up to 3-5% of strokes. Subject to the affected ACA branches, different clinical patterns can be defined. We report a case series of patients with isolated infarctions of the pericallosal (PC) artery territory. We analyzed 36 consecutive patients presenting over a 10-year period with isolated PC artery territory infarctions (15 left-sided, 19 right-sided, 2 bilateral) regarding clinical symptoms as well as MRI findings. Analysis of DWI lesion pattern showed complete PC artery infarctions in three patients. The majority of patients had partial infarctions predominantly involving either the superior frontal gyrus (n = 12), the corpus callosum (n = 1) or both (n = 20). Hemodynamic lesion patterns were found in 13 patients, while multiple cortical emboli occurred in six. Distal pathology of the ACA (n = 13) was the most frequent MRA finding. Core symptom was contralateral hemiparesis with lower limb predominance (n = 29), partly associated with early-onset spasticity. Interestingly, motor evoked potential recording was abnormal in only five patients. Further characteristic symptoms were psychomotor slowing (n = 9), often with speech disturbances such as decreased verbal fluency, and confusional state (n = 4). Visual or motor hemineglect (n = 5) as well as apraxia (n = 5) was confined to a few patients only. Pericallosal artery infarctions are a rare localization of stroke, mostly occurring as partial infarctions due to distal ACA pathology. Clinically, they are mainly characterized by hemiparesis predominately in the lower limb caused by involvement of supplementary motor cortex areas without affection of the corticospinal tract.

Lesions of the premotor and supplementary motor areas fail to prevent implicit learning in the operant serial implicit learning task

An implicit learning deficit in people with Huntington's or Parkinson's diseases has implicated the striatum as being of importance for non-declarative learning. We have sought to identify the neurological substrate of this function using a Serial Implicit Learning Task (SILT), an operant task that requires the animal to produce 2-phase (S1 and S2) sequential nose pokes to receive a reward in the nine-hole box apparatus. Differences in performance on the speed and accuracy of responding to stimuli occurring in predictable locations over those to unpredictable locations provide an index of implicit learning, within the context of generalised performance of a skilled motor habit. Previous studies with striatal lesions demonstrated clear functional deficits on the SILT that implicated a generalised impairment in the speed and accuracy of skilled motor performance, whereas the specific implicit learning component of the task remained intact. Since imaging studies in man have identified the premotor and supplementary motor area (SMA) of the cortex as being of importance in implicit learning, we here explore the effects of similar lesions in animals on performance of the SILT. Premotor and SMA lesions produced a generalised impairment in both the accuracy and reaction time measures of SILT performance, whereas – like striatal lesions – they remained able to utilise the benefit of predictable information. A similar profile of impairments was apparent both in animals pretrained on the task prior to lesion, and in animals trained under acquisition post-lesion. The presented results suggest that the premotor and SMA are not essential for implicit learning, but are important in the performance of sequenced motor tasks.

Encoding of speed and direction of movement in the human supplementary motor area

The supplementary motor area (SMA) plays an important role in planning, initiation, and execution of motor acts. Patients with SMA lesions are impaired in various kinematic parameters, such as velocity and duration of movement. However, the relationships between neuronal activity and these parameters in the human brain have not been fully characterized. This is a study of single-neuron activity during a continuous volitional motor task, with the goal of clarifying these relationships for SMA neurons and other frontal lobe regions in humans. The participants were 7 patients undergoing evaluation for epilepsy surgery requiring implantation of intracranial depth electrodes. Single-unit recordings were conducted while the patients played a computer game involving movement of a cursor in a simple maze. In the SMA proper, most of the recorded units exhibited a monotonic relationship between the unit firing rate and hand motion speed. The vast majority of SMA proper units with this property showed an inverse relation, that is, firing rate decrease with speed increase. In addition, most of the SMA proper units were selective to the direction of hand motion. These relationships were far less frequent in the pre-SMA, anterior cingulate gyrus, and orbitofrontal cortex. The findings suggest that the SMA proper takes part in the control of kinematic parameters of endeffector motion, and thus lend support to the idea of connecting neuroprosthetic devices to the human SMA.

Impaired control of an action after supplementary motor area lesion: a case study

The kinematics of the action formed by reaching–grasping an object and placing it on a second target was studied in a patient who suffered from an acute vascular left brain lesion, which affected the Supplementary Motor Area proper (SMA-proper) (Matelli M, Luppino G. Thalamic input to mesial and superior area 6 in the macaque monkey. Journal of Comparative Neurology 1996;372:59–87, Matelli M, Luppino G, Fogassi L, Rizzolatti G. Thalamic input to inferior area 6 and area 4 in the macaque monkey. Journal of Comparative Neurology 1989;280:468–488), and in five healthy control subjects. The reach kinematics of the controls was affected by the positions of both the reaching–grasping and the placing targets (Gentilucci M, Negrotti A, Gangitano M. Planning an action. Experimental Brain Research 1997;115:116–28). In contrast, the reach kinematics of the patient was affected only by the position of the reaching–grasping target. By comparing these results with those previously found in Parkinson’s disease patients executing the same action (Gentilucci M, Negrotti A. Planning and executing an action in Parkinson’s disease patients. Movement Disorders 1999;1:69–79, Gentilucci M, Negrotti A. The control of an action in Parkinson’s disease. Experimental Brain Research 1999;129:269–277), we suggest that the anatomical “motor” circuit formed by SMA-proper (see above), Basal Ganglia (BG) and Thalamus (Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends in the Neurosciences 1990;13:266–271, Hoover JE, Strick PL. Multiple output channels in the basal ganglia. Nature 1993;259:819–821) may be involved in the control of actions: SMA-proper assembles the sequence of the action, whereas BG updates its parameters and stores them.

Who tells one hand what the other is doing: the neurophysiology of bimanual movements.

Research into neural mechanisms of bimanual coordination sheds light on questions raised by psychophysics. While the results we review are merely suggestive, the overall structure of the neural mechanisms may be emerging slowly.Different mechanisms may serve the spatial and temporal coupling of bimanual movements. Temporal coupling depends on a lateralized pace-keeping mechanism possibly associated with spinal CPGs, is preferentially controlled by the dominant hemisphere, and does not depend directly on the corpus callosum. Spatial coupling, in contrast, arises through interhemispheric interaction. Individual neurons in each hemisphere reflect this interaction, as does interhemispheric synchronization. The interaction allows decoupling of the arms, as substantiated by the PV analysis. Furthermore, bimanual proximal arm movements and finger movements are controlled differently, as shown in differences in the patterns of neural activity in M1 and SMA.Taken as a whole, the research we review has not yet culminated in a conclusive model. However, by combining psychophysics and neurophysiology, we raise concrete, testable hypotheses that may help realize this goal.*To whom correspondence should be addressed (e-mail: eilon@hbf.huji.ac.il).

Combined deficits of saccades and visuo-spatial orientation after cortical lesions.

Functionally, saccadic eye movements are closely linked to visuo-spatial orientation. Anatomically, the network of cortical areas controlling saccades also seems to be involved in spatial attention and orientation. Consequently, lesions should cause deficits in both categories. We investigated this in 34 patients with focal unilateral lesions of the posterior parietal cortex (PPC), the frontal eye fields (FEF), the supplementary motor area (SMA), or the dorsolateral prefrontal cortex (PFC). Saccadic eye movements were recorded using infrared reflection oculography. Visual hemineglect or other visuo-spatial disorders were investigated by a series of standardized paper-pencil tests. Further, the internal spatial coordinates (subjective visual vertical and subjective straight ahead) were assessed psychophysically. Depending on the site of the lesion, different patterns of deficits were identified: lesions of the PPC impaired reflexive exploration of visual space in terms of delayed and hypometric visually triggered saccades into the contralesional hemifield, related to the severity of visual hemineglect. Further, PPC lesions specifically affected basic functions of the perceptual analysis of space, such as the internal spatial coordinates and spatial constancy across saccades. The latter was tested by applying visual double-step stimuli, where saccade-related extraretinal information had to be taken into account for achieving spatial accuracy. Frontal lesions left these functions intact. FEF lesions, however, impaired systematic intentional exploration of space, thus causing an exploratory-motor type of visual hemineglect. Prefrontal (PFC) lesions impaired the working memory for saccade-related spatial information, and SMA lesions affected temporal properties such as the timing of saccadic sequences, but did not cause specific visuo-spatial deficits. In conclusion, patients with frontal or parietal cortical lesions often exhibit combined saccadic and visuo-spatial disorders, most of which are topically specific.

Bilateral Anarchic Hand in a Single Case Report

The course of a patient affected by the phenomenon of "anarchic hand" (AH) is de scribed. The patient had an ischemic lesion involving the left frontomesial cortex and the corpus callosum with a transitory AH of the left hand and later a chronic right AH. The signs of callosal disconnection and the involvement of the supplementary motor area were reviewed, and various hypotheses as to the nature of the lesion that causes the AH phenomenon to appear and to last have been discussed. The hypoth esis that a callosal lesion is sufficient for the appearance of AH, but a supplementary motor area lesion contralateral to the involved hand causes the chronic AH syndrome. Key Words: Anarchic hand—Supplementary motor area—Corpus callosum—Cal— losal disconnection signs.

The role of the supplementary motor area in the control of voluntary movement

The contribution of the supplementary motor area (SMA) to the preparation of voluntary movement has been revealed by various experimental methods. These include studies of movement-related cortical potentials recorded from surface and subdural electrodes, extracellular recordings from SMA neurones in monkeys, studies of regional cerebral blood flow, clinical studies of movement deficits associated with SMA lesions and disruption of basal ganglia output to the SMA in Parkinson's disease. The SMA is found to be especially involved in self-paced, or well-learnt and predictable movements which can be internally-determined. In Parkinsonian subjects, however, the SMA is only involved in non-cued movements which must be internally-de-termined; this may reflect both the reliance on external cues, and the deficit in using internal predictive models to guide movement, which are associated with Parkinson's disease. SMA involvement is also more reliant upon timing than on spatial cues, indicating its role in the temporal organisation of sequential movements, rather than the programming of spatial movement parameters. These observations suggest an internal-cuing mechanism, involving interaction between the SMA and the basal ganglia to mediate the temporal organisation of voluntary and internally-determined sequential movement.

Treatment of Supplementary Motor Area Syndrome

Supplementary motor area syndrome is characterized by impaired initiation of volitional movement and commonly occurs following dominant or bilateral supplementary motor area (SMA) lesions. Initiation deficit is extremely disruptive to functional performance due to the pervasive nature of the impairment. We present a functional treatment approach, based on a Lurian model of neuropsychological intervention, involving the verbal regulation of movement. Using a single-case experimental design (i.e., extended ABAB), involving planned intermittent treatment withdrawal, we treated the severe initiation deficit of a 53-year-old male with supplementary motor area syndrome, secondary to a dominant SMA lesion. Significant gains were demonstrated in response latency, time to completion of multiple-step upper limb movements, activities of daily living (ADL), and mobility. Despite severely impaired initiation, the patient was able to learn and independently utilize a structured cuing sequence, which significantly incre...

Impairment of sequences of memory‐guided saccades after supplementary motor area lesions

Different paradigms of saccades were recorded electro-oculographically in 2 patients with infarction affecting the left supplementary motor area. Saccades made toward visual targets (visually-guided saccades) or away from them (antisaccades) were normal in both patients. Memory-guided saccades, made to the remembered position of a flash occurring 2 seconds before, were preserved in 1 patient and only slightly impaired in the other. However, sequences of two or three memory-guided saccades were severely impaired in both patients. It has previously been reported that the supplementary motor area plays an important role in programming sequential limb movements. Our data suggest that this area plays a similar role in the control of sequential eye movements.

Bereitschaftspotential in patients with unilateral lesions of the supplementary motor area.

In the present study, an attempt was made to examine the sensitivity of the Bereitschaftspotential (BP) preceding simple finger movement in revealing pathophysiological patterns of premovement cortical activity in patients with chronic unilateral lesions of the supplementary motor area (SMA). Usually, in healthy subjects, BP has a clear maximum in Cz with larger amplitudes than in Ccon (located over the motor cortex, contralateral to the performing hand). In the patients, amplitudes did not differ between Cz and Ccon. This effect of the lesion on BP topography, was found in movements of either side. However, intraindividual comparisons revealed that the reduction of the BP in Cz (relative to Ccon) was larger for movements contralateral to the SMA lesion than for those ipsilateral of it.

Modulation of the long-latency reflex to stretch by the supplementary motor area in humans

Surface-recorded, electromyographic responses to 200-ms ramp stretches were studied in the wrist flexor muscles from both arms of a patient with clinical and radiographic evidence of infarction in the right supplementary motor area (SMA). They were compared with those from 8 age-matched control subjects. The latencies of the spinal component of the stretch reflex were slightly longer than normal in both arms of the patient (normal subjects: 28.5±2.6 ms; patient: 35 ms, right arm and 32 ms left arm). However, the amplitude and duration of the short-latency response were identical in both arms. The onset of the long-latency response to stretch was symmetrical in both the patient's arms and was slightly later than normal (normal subjects 55.5±4.0 ms, patient: 72 ms right arm and 70 ms left arm); however, its duration was considerably prolonged in the arm contralateral to the SMA lesion (normal subjects: 44.8±6.0 ms; patient: 48 ms right arm, 105 ms left arm). These results are consistent with the hypothesis that the long-latency stretch reflex is mediated via a transcortical loop.

Lesions in supplementary motor area interfere with a monkey's performance of a bimanual coordination task

Unilateral lesions of the supplementary motor area (SMA) produce a deficit in bimanual coordination which is long-lasting. Both hands tend to be used in an identical manner instead of sharing the work load between them. This finding seems to be consistent with a role of SMA in the programming of movement through instruction of the primary motor area.

Neurological deficiencies following supplementary motor area lesions in Macaca mulatta.

Neurological deficiencies following supplementary motor area lesions in Macaca mulatta.