TMS evidence for smooth pursuit gain control by the frontal eye fields

Smooth pursuit eye movements are used to continuously track slowly moving visual objects. A peculiar property of the smooth pursuit system is the nonlinear increase in sensitivity to changes in target motion with increasing pursuit velocities. We investigated the role of the frontal eye fields (FEFs) in this dynamic gain control mechanism by application of transcranial magnetic stimulation. Subjects were required to pursue a slowly moving visual target whose motion consisted of 2 components: a constant velocity component at 4 different velocities (0, 8, 16, and 24 deg/s) and a superimposed high-frequency sinusoidal oscillation (4 Hz, +/-8 deg/s). Magnetic stimulation of the FEFs reduced not only the overall gain of the system, but also the efficacy of the dynamic gain control. We thus provide the first direct evidence that the FEF population is significantly involved in the nonlinear computation necessary for continuously adjusting the feedforward gain of the pursuit system. We discuss this with relation to current models of smooth pursuit.     

Eye-pursuit and reafferent head movement signals carried by pursuit neurons in the caudal part of the frontal eye fields during head-free pursuit

Eye and head movements are coordinated during head-free pursuit. To examine whether pursuit neurons in frontal eye fields (FEF) carry gaze-pursuit commands that drive both eye-pursuit and head-pursuit, monkeys whose heads were free to rotate about a vertical axis were trained to pursue a juice feeder with their head and a target with their eyes. Initially the feeder and target moved synchronously with the same visual angle. FEF neurons responding to this gaze-pursuit were tested for eye-pursuit of target motion while the feeder was stationary and for head-pursuit while the target was stationary. The majority of pursuit neurons exhibited modulation during head-pursuit, but their preferred directions during eye-pursuit and head-pursuit were different. Although peak modulation occurred during head movements, the onset of discharge usually was not aligned with the head movement onset. The minority of neurons whose discharge onset was so aligned discharged after the head movement onset. These results do not support the idea that the head-pursuit-related modulation reflects head-pursuit commands. Furthermore, modulation similar to that during head-pursuit was obtained by passive head rotation on stationary trunk. Our results suggest that FEF pursuit neurons issue gaze or eye movement commands during gaze-pursuit and that the head-pursuit-related modulation primarily reflects reafferent signals resulting from head movements.     

The location probability effects of saccade reaction times are modulated in the frontal eye fields but not in the supplementary eye field

The visual system constantly utilizes regularities that are embedded in the environment and by doing so reduces the computational burden of processing visual information. Recent findings have demonstrated that probabilistic information can override attentional effects, such as the cost of making an eye movement away from a visual target (antisaccade cost). The neural substrates of such probability effects have been associated with activity in the superior colliculus (SC). Given the immense reciprocal connections to SC, it is plausible that this modulation originates from higher oculomotor regions, such as the frontal eye field (FEF) and the supplementary eye field (SEF). To test this possibility, the present study employed theta burst transcranial magnetic stimulation (TMS) to selectively interfere with FEF and SEF activity. We found that TMS disrupted the effect of location probability when TMS was applied over FEF. This was not observed in the SEF TMS condition. Together, these 2 experiments suggest that the FEF plays a critical role not only in initiating saccades but also in modulating the effects of location probability on saccade production.     

Involvement of the cerebellar dorsal vermis in vergence eye movements in monkeys

Frontal-eyed primates use both smooth pursuit in frontoparallel planes (frontal pursuit) and pursuit-in-depth (vergence pursuit) to track objects moving slowly in 3-dimensional (3D) space. To understand how 3D-pursuit signals represented in frontal eye fields are processed further by downstream pathways, monkeys were trained to pursue a spot moving in 3D virtual space. We characterized pursuit signals in Purkinje (P) cells in the cerebellar dorsal vermis and their discharge during vergence pursuit. In 41% of pursuit P-cells, 3D-pursuit signals were observed. However, the majority of vermal-pursuit P-cells (59%) discharged either for vergence pursuit (43%) or for frontal pursuit (16%). Moreover, the majority (74%) of vergence-related P-cells carried convergence signals, displaying both vergence eye position and velocity sensitivity during sinusoidal and step vergence eye movements. Preferred frontal-pursuit directions of vergence + frontal-pursuit P-cells were distributed in all directions. Most pursuit P-cells (73%) discharged before the onset of vergence eye movements; the median lead time was 16 ms. Muscimol infusion into the sites where convergence P-cells were recorded resulted in a reduction of peak convergence eye velocity, of initial convergence eye acceleration, and of frontal-pursuit eye velocity. These results suggest involvement of the dorsal vermis in conversion of 3D-pursuit signals and in convergence eye movements.     

Midazolam for caudal analgesia in children: comparison with caudal bupivacaine

In a randomized, double-blind study we have examined the analgesic efficacy of caudal administration of midazolam, bupivacaine, or a mixture of both drugs in 45 children, undergoing inguinal herniotomy. They were allocated randomly into three groups (n = 15 in each) to receive a caudal injection of either 0.25% bupivacaine 1 ml · kg^?1 with or without midazolam 50 μg · kg^?1 or midazolam 50 μg · kg^?1 with normal saline 1 ml · kg^?1. There were no differences in quality of pain relief, postoperative behaviour or analgesic requirements between the midazolam group and the other two groups. Times to first analgesic administration (paracetamol suppositories) were longer (P < 0.001) in the bupivacaine-midazolam group than in the other two groups. Further, the bupivacaine-midazolam group received fewer (P < 0.05) doses of paracetamol than the bupivacaine group. Side effects such as motor weakness, respiratory depression or prolonged sedation were not observed in patients who received caudal epidural midazolam only. We conclude that caudal midazolam in a dose of 50 μg · kg^?1 provides equivalent analgesia to bupivacaine 0.25%, when administered postoperatively in a volume of 1 ml · kg^?1 for children following unilateral inguinal hemiotomy.

     

Segregation of visual selection and saccades in human frontal eye fields

The premotor theory of attention suggests that target processing and generation of a saccade to the target are interdependent. Temporally precise transcranial magnetic stimulation (TMS) was delivered over the human frontal eye fields, the area most frequently associated with the premotor theory in association with eye movements, while subjects performed a visually instructed pro-/antisaccade task. Visual analysis and saccade preparation were clearly separated in time, as indicated by 2 distinct time points of TMS delivery that resulted in elevated saccade latencies. These results show that visual analysis and saccade preparation, although frequently enacted together, are dissociable processes.     

An anatomical landmark for the supplementary eye fields in human revealed with functional magnetic resonance imaging.

Together with the frontal and parietal eye fields, the supplementary eye field (SEF) is involved in the performance and control of voluntary and reflexive saccades and of ocular pursuit. This region was first described in non-human primates and is rather well localized on the dorsal surface of the medial frontal cortex. In humans the site of the SEF is still ill-defined. Functional imaging techniques have allowed investigation of the location and function of the SEF. However, there is great variability with regard to the published standardized coordinates of this area. We used here the spatial precision of functional magnetic resonance imaging (fMRI) in order to better localize the SEF in individuals. We identified as the SEF a region on the medial wall that was significantly activated when subjects executed self-paced horizontal saccades in darkness as compared to rest. This region appeared to be predominantly activated in the left hemisphere. We found that, despite a discrepancy of >2 cm found in the standardized Talairach coordinates, the location of this SEF-region could be precisely and reliably described by referring to a sulcal landmark found in each individual: the upper part of the paracentral sulcus.     

Temporal evolution and strength of neural activity in parietal cortex during eye and hand movements

The role of area 7a in eye-hand movement was studied by recording from individual neurons while monkeys performed 7 different tasks, aimed at assessing the relative influence of retinal, eye, and hand information on neural activity. Parietal cell activity was modulated by visuospatial signals about target location, as well as by information concerning eye and/or hand movement, and position. The highest activity was elicited when the hand moved to the fixation point. The population activities across different memory tasks showed common temporal peaks when aligned to the visual instruction (visuospatial peak) or Go signal (motor peak) for eye, hand, and coordinated eye-hand movement. The motor peak was higher for coordinated eye-hand movement, and it was absent in a No-Go task. Two activation maxima were also observed during visual reaching. They had the same latency of the visuospatial and motor peaks seen in the memory tasks. Therefore, area 7a seems to operate through a common neural mechanism underlying eye, hand, or combined eye-hand movement. This mechanism is revealed by invariant temporal activity profiles and is independent from the effector selected and from the presence or absence of a visible target during movement. For comparative purposes, we have studied the temporal evolution of the population activity in the superior parietal lobule (SPL) during the same reaching tasks and during a saccade task. In SPL, the population activity was characterized by a single peak, time locked to the Go signal for eye, hand, or combined eye-hand movement. As in IPL, the time of occurrence of this peak was effector independent. The population activity remained unchanged when the position of the eye changed, suggesting that SPL is mostly devoted to the hand motor behavior.     

Activation of the supplementary motor area (SMA) during performance of visually guided movements

The supplementary motor area (SMA) has long been thought to have a special role in the internal generation of complex movements. Yet, a number of recent functional imaging studies indicate that the SMA is activated during the execution of simple movements guided by sensory cues. The extent of participation of the cingulate motor areas in visually guided movements also is unclear. To explore these issues we used the 2-deoxyglucose (2DG) technique to measure functional activation in the motor areas on the medial wall of the hemisphere in monkeys trained to perform visually guided reaching movements to randomly presented targets. This approach enabled us to make precise comparisons between sites of activation and the location of specific premotor areas on the medial wall of the hemisphere. We found that the SMA was strongly activated during reaching to different visual targets. Indeed, its activation was comparable to that of the primary motor cortex (M1). In contrast, none of the cingulate motor areas displayed significantly increased activation specifically related to arm movements. Our results provide further support for the involvement of the SMA in visually guided movements. Furthermore, our observations suggest that during externally guided reaching, SMA activation is tightly coupled to that of M1, but dissociated from that of the cingulate motor areas.     

Levobupivacaine caudal anesthesia in children: a randomized double-blind comparison with bupivacaine

BACKGROUND: Levobupivacaine is the pure S-enantiomer of bupivacaine. Despite obvious benefits in the event of accidental intravascular injection there has been no studies demonstrating a clinically significant benefit to levobupivacaine over racemic bupivacaine for pediatric regional anesthesia. Given the similar pharmacokinetic profiles of both drugs the studies to date have been underpowered to demonstrate what is likely to be a small difference in clinical effectiveness. Our aim was to determine if there are significant differences in the clinical effectiveness of levobupivacaine compared with racemic bupivacaine for caudal anesthesia in children having lower abdominal surgery. A secondary aim was to determine if there are differences in the incidence of postoperative motor blockade between these agents. METHODS: Three hundred and ten children ranging in age from 1 month to 10.75 years in age having lower abdominal surgery were enrolled. Patients were randomized in a double blind manner to receive a caudal block with either 0.25% bupivacaine (n = 152) or 0.25% levobupivacaine (n = 155) to a total volume of 1 ml x kg(-1). Motor blockade (modified Bromage scale) and postoperative pain or distress (FLACC behavioral scale for postoperative pain) were measured at predetermined time points during the subsequent 120 min. RESULTS: There were no significant adverse effects attributable to levobupivacaine. Success rates were defined as a lack of hemodynamic response to first surgical incision and low postoperative pain scores. At a mean duration of 5 min between block completion and first incision success for 1 ml x kg(-1) of 0.25% bupivacaine was 91% and 94% for 0.25% levobupivacaine. Satisfactory postoperative analgesia was present in 98% of patients after bupivacaine caudal anesthesia and 97.5% for levobupivacaine. At 30 min following caudal anesthesia the incidence of postoperative motor block with racemic bupivacaine was 84% and decreased to 7% at 120 min. For levobupivacaine motor block at 30 min postcaudal was present in 85% and decreased to 11% at 120 min. CONCLUSIONS: Levobupivacaine is an effective agent for caudal anesthesia in children at a recommended dose of 2.5 mg x kg(-1). The rapidity of onset was suitable for establishment of surgical anesthesia and postoperative analgesia was achieved in greater than 97.5% of patients. It appears to be of equivalent potency to racemic bupivacaine in children requiring lower abdominal surgery.     

累及补充运动区额上回胶质瘤的外科治疗

目的　探讨累及补充运动区额上回胶质瘤的外科治疗。方法　对 16例累及补充运动区的低级别星形细胞瘤患者的临床资料及随访结果进行分析。结果　手术切除范围距中央前沟 >1cm的病变 8例 ,其中 6例表现为补充运动区综合征 ,虽出现暂时的运动和语言功能障碍 ,但随访 12个月 ,均得到恢复 ;而手术切除范围距中央前沟 <1cm的 8例病变 ,术后均立即出现对侧肢体偏瘫 ,随访 12个月 ,仍有 5例遗留运动障碍。结论　对于累及补充运动区的额上回胶质瘤 ,当手术切除范围距中央前沟 <1cm时 ,很可能造成永久性的功能障碍     

Modulation of visual responses in macaque frontal eye field during covert tracking of invisible targets

The purpose of this study was to investigate the interaction between internal representations of invisible moving targets and visual responses of neurons in frontal eye fields (FEFs). Monkeys were trained to make saccades to the extrapolated position of a target that was temporarily rendered invisible for variable durations as if it had passed behind an occluder. Flashed, task-irrelevant visual probe stimuli were used to study the visual responsiveness of FEF neurons during this task. Probes were flashed at various times and locations during the occlusion interval. Net changes in neuronal activity were obtained by comparing the activity on trials with probes with randomly interleaved trials without any probe. Most neurons showed an increase in firing rate in response to the probe, but some showed a decrease. Both types of responses were enhanced when the invisible target moved toward the receptive field (RF) as compared with trials on which the target moved away from the RF. Some neurons showed a spatial shift in the visual response during the occlusion interval. For cells that were excited by the probe, the shift tended to be correlated with the direction of motion of the target, whereas for cells that were inhibited the shift tended to be in the opposite direction. These results suggest that the role of FEF in predicting invisible target motion includes a sensory/perceptual component.     

Localization of human frontal eye fields: anatomical and functional findings of functional magnetic resonance imaging and intracerebral electrical stimulation.

OBJECT: The goal of this study was to investigate the anatomical localization and functional role of human frontal eye fields (FEFs) by comparing findings from two independently conducted studies. METHODS: In the first study, 3-tesla functional magnetic resonance (fMR) imaging was performed in 14 healthy volunteers divided into two groups: the first group executed self-paced voluntary saccades in complete darkness and the second group repeated newly learned or familiar sequences of saccades. In the second study, intracerebral electrical stimulation (IES) was performed in 38 patients with epilepsy prior to surgery, and frontal regions where stimulation induced versive eye movements were identified. These studies showed that two distinct oculomotor areas (OMAs) could be individualized in the region classically corresponding to the FEFs. One OMA was consistently located at the intersection of the superior frontal sulcus with the fundus of the superior portion of the precentral sulcus, and was the OMA in which saccadic eye movements could be the most easily elicited by electrical stimulation. The second OMA was located more laterally, close to the surface of the precentral gyrus. The fMR imaging study and the IES study demonstrated anatomical and stereotactic agreement in the identification of these cortical areas. CONCLUSIONS: These findings indicate that infracentimetric localization of cortical areas can be achieved by measuring the vascular signal with the aid of 3-tesla fMR imaging and that neuroimaging and electrophysiological recording can be used together to obtain a better understanding of the human cortical functional anatomy.     

Preoperative mapping of the supplementary motor area in patients harboring tumors in the medial frontal lobe

OBJECT: Injury to the supplementary motor area (SMA) is thought to be responsible for transient motor and speech deficits following resection of tumors involving the medial frontal lobe. Because direct intraoperative localization of SMA is difficult, the authors hypothesized that functional magnetic resonance (fMR) imaging might be useful in predicting the risk of postoperative deficits in patients who undergo resection of tumors in this region. METHODS: Twelve patients who had undergone fMR imaging mapping while performing speech and motor tasks prior to excision of their tumor, that is, based on anatomical landmarks involving the SMA, were included in this study. The distance between the edge of the tumor and the center of SMA activation was measured and was correlated with the risk of incurring postoperative neurological deficits. In every patient, SMA activation was noted in the superior frontal gyrus on preoperative fMR imaging. Two speech and two motor deficits typical of SMA injury were observed in three of the 12 patients. The two speech deficits occurred in patients with tumors involving the dominant hemisphere, whereas one of the motor deficits occurred in a patient with a tumor in the nondominant hemisphere. The risk of developing a postoperative speech or motor deficit was 100% when the distance between the SMA and the tumor was 5 mm or less. When the distance between SMA activation and the lesion was greater than 5 mm, the risk of developing a motor or a speech deficit was 0% (p = 0.0007). CONCLUSIONS: Early data from this study indicated that fMR imaging might be useful in localizing the SMA and in determining the risk of postoperative deficits in patients who undergo resection of tumors located in the medial frontal lobe.     

Pre-emptive analgesia: comparison of preoperative with postoperative caudal block on postoperative pain in children

We have compared in 25 children the effect of preoperative withpostoperative caudal block on pain after circumcision in a double-blind,randomized study. After induction of anaesthesia, patients wereallocated randomly to receive a caudal block either before (n= 14) or immediately after (n = 11) surgery. Postoperative painwas rated on a paediatric pain scale. If pain occurred, childrenreceived paracetamol in a dose related to body weight. Usingthe Mann-Whitney U test (significance     

An additional motor-related field in the lateral frontal cortex of squirrel monkeys

Our earlier efforts to document the cortical connections of the ventral premotor cortex (PMv) revealed dense connections with a field rostral and lateral to PMv, an area we called the frontal rostral field (FR). Here, we present data collected in FR using electrophysiological and anatomical methods. Results show that FR contains an isolated motor representation of the forelimb that can be differentiated from PMv based on current thresholds and latencies to evoke electromyographic activity using intracortical microstimulation techniques. In addition, FR has a different pattern of cortical connections compared with PMv. Together, these data support that FR is an additional, previously undescribed motor-related area in squirrel monkeys.     

Electromyographic activity in the immobilized shoulder girdle musculature during contralateral upper limb movements

The purpose of this study was to quantify electromyographic (EMG) activity in the immobilized shoulder girdle musculature at rest and during a battery of contralateral upper limb activities. Six asymptomatic men, aged 22 to 33 years, volunteered to participate. Fine-wire (supraspinatus, infraspinatus) and surface (deltoids, trapezii, biceps, serratus anterior) electrodes recorded the mean peak normalized (percent maximal voluntary contraction [%MVC]) EMG activity from each immobilized muscle at rest and during slow, fast, and incrementally resisted contralateral upper limb motions (5, 15, and 25 lb). EMG activity in all muscles was low during quiet immobilized standing (<1.5% maximal voluntary contraction [MVC]). During slow contralateral upper limb motions, activity ranged from 0.7% to 51.6% MVC (highest in trapezii) and was less than 15% MVC in the supraspinatus, infraspinatus, and anterior deltoid. Bimanual jar opening increased biceps activity from 7.8% to 16.1% MVC. During fast contralateral upper limb motions, peak infraspinatus activity increased to 56.7% during a fast straightforward reach. Supraspinatus activity was relatively high during all resisted backward-pulling motions (25.2%-32.1% MVC), whereas resisted forward reaching produced relatively little activity in the anterior deltoid, supraspinatus, infraspinatus, or biceps. Several slow and fast motions produced high trapezius activity (>45% MVC) with low supraspinatus, biceps, and anterior deltoid activities (<10% MVC). Our findings suggest that (1) immobilized shoulder girdle muscle EMG activity during quiet standing is negligible in asymptomatic individuals; (2) contralateral upper limb motions at self-selected speeds are not likely to be harmful to healing tissues; (3) during early healing periods, patients with biceps-labral injury should minimize bimanual activities, those with supraspinatus injury should avoid backward-pulling motions, and those with infraspinatus injury should avoid fast straightforward reaches; and (4) cross-body, straightforward, or downward reaches at either a slow or fast speed may be appropriately prescribed as rehabilitative exercises that can be initiated while the shoulder remains immobilized.     

Effect of ilioinguinal nerve block on the catecholamine plasma levels in orchidopexy: comparison with caudal epidural block

BACKGROUND: Both caudal epidural and ilioinguinal/iliohypogastric nerve blocks have been used to provide effective intra- and postoperative analgesia. Stress response hormone levels can be used as an objective method to assess the analgesic efficacy of the anaesthetic techniques used in infraumbilical surgery in children. In this study, we compared catecholamine blood levels in children undergoing these two different supplementary analgesic/anaesthetic techniques. METHODS: Thirty male paediatric patients undergoing orchidopexy, ASA I, received inhalation general anaesthesia, and were randomly allocated to one of two groups: a caudal group (n = 15) and an ilioinguinal/iliohypogastric nerve block group (n = 15). Plasma epinephrine and norepinephrine concentrations were measured at the induction time, at the end of surgery, and in the postanaesthesia care unit. Postoperative pain score was also assessed in the postanaesthesia care unit. Results: In both groups, there was a substantial decrease in the catecholamine blood levels; however, there were significantly higher levels of epinephrine in the ilioinguinal group at the end of surgery (P = 0.008) and in the recovery room (P = 0.02) and a significant higher level of norpinephrine in the recovery room (P = 0.008). CONCLUSIONS: The result of this study revealed that caudal epidural block was more effective than ilioinguinal block in suppressing the stress response as reflected in epinephrine and norepinephrine blood levels in orchidopexy patients.     

Caudal morphine for postoperative analgesia in children: a comparison with caudal bupivacaine and intravenous morphine

We compared the efficacy, duration, and side effects of preservative-free morphine injected into the caudal space in children, with caudal bupivacaine and with intravenous morphine administration for relief of postoperative pain. Forty-six children, ages 1-16 yr, were randomly assigned to receive intravenous morphine (control group), caudal bupivacaine (0.25%, 1 ml/kg), or caudal morphine (0.5 mg/ml, 0.1 mg/kg). In half the patients given caudal morphine, the morphine was mixed with a dose of lidocaine adequate to produce sacral analgesia, to confirm correct caudal injection of the morphine. Caudal injections were performed at the end of surgery. Time until the first required postoperative intravenous morphine dose was recorded for each patient. The duration of analgesia was significantly greater with caudal morphine (median 12 hr, P less than 0.02) than with caudal bupivacaine (median 5 hr), and both were greater than with intravenous morphine in control patients (median 45 min). Urinary retention, pruritis, and nausea appeared with slightly greater frequency in the caudal morphine group, but no delayed respiratory depression occurred. Caudal morphine (0.5 mg/ml, 0.1 mg/kg) provided 8-24 hr of analgesia in children without a significantly greater incidence of side effects than caudal bupivacaine or intravenous morphine.