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Biomedical subjects

R M Müri

Publications and source records attributed to R M Müri.

At least 19 recordsLinked to original sources

Lateralized and frequency-dependent effects of prefrontal rTMS on regional cerebral blood flow.

Repetitive transcranial magnetic stimulation (rTMS) is a means to study the function and connectivity of brain areas. The present study addressed the question of hemispheric asymmetry of frontal regions and aimed to further understand the acute effects of high- and low-frequency rTMS on regional cerebral blood flow (rCBF). Sixteen healthy right-handed men were imaged using H(2)(15)O positron emission tomography (PET) immediately after stimulation. High (10 Hz)- and low (1 Hz)-frequency suprathreshold short-duration rTMS was applied over either the left or right dorsolateral prefrontal cortex (DLPFC). Slow and fast rTMS applied over the left DLPFC significantly increased CBF in the stimulated area. Compared to baseline, slow rTMS induced a significant increase in CBF contralateral to the stimulation site, in the right caudate body and in the anterior cingulum. Furthermore, slow rTMS decreased CBF in the orbitofrontal cortex (OFC, ipsilateral to stimulation side). Fast rTMS applied over the right DLPFC was associated with increased activity at the stimulation site, in the bilateral orbitofrontal cortex and in the left medial thalamus compared to 1-Hz rTMS. These results show that rCBF changes induced by prefrontal rTMS differ upon hemisphere stimulated and vary with stimulation frequency. These differential neurophysiological effects of short-train rTMS with respect to side and frequency suggest hemisphere-dependent functional circuits of frontal cortico-subcortical areas.

Adult↗

[A new method of visual exploration analysis].

The term visual field corresponds to the angular field of view that is seen by the eyes when they are fixed on a point straight-ahead. In neurological patients--e.g. stroke, trauma, or tumour patients--visual field function can be restricted, depending on lesion site and size. In contrast, the term "functional visual field" describes the area of visual field responsiveness under more ordinary viewing conditions. The visual exploration, i.e. the capacity to explore and analyze our visual world, is dependent on the integrity of the visual system and the oculomotor system which has to move the fovea from one object of interest to the next. In this paper, we present a new method to assess the functional visual field, conceptualized as the area that a patient actively scans with eye movements to detect predefined targets placed on everyday scenes. This method allows us to compare three levels of visual field function: (a) the spatial distribution of successful search (hits, i.e. which targets did the patient find?), (b) the spatial distribution of fixations (i.e. where did the patient preferentially search for targets?), and (c) the retinotopic level (i.e. the visual field assessed by perimetry). By integrating these three levels, one can evaluate functional outcomes of visual field disorders. Of particular importance is the question of how a patient compensates for a visual field loss with appropriate eye movements. A further clinical application of this method is the comparison of pre- with post-treatment data. Patients with visual field disorders usually undergo specific exploration trainings, aimed at enhancing the number and amplitude of saccades towards the region of the visual field deficit. The first experiences and clinical application with this method are presented here.

Eye Movements↗

[Intermittent diplopia after prolonged downward gaze to the right: what is the differential diagnosis?].

In general, intermittent diplopia evokes suspicion of ocular myasthenia gravis. However, other etiologies such as Brown syndrome or myokymia of the superior oblique may provoke intermittent diplopia. We present a case of intermittent diplopia due to a tumor in the cavernous sinus. A 59-year-old patient reported intermittent diplopia after prolonged downward gaze to the right. All other gaze directions failed to provoke symptoms. In 1992, the diagnosis of inactive macroadenoma of the pituitary gland was established and the patient underwent surgery and radiation therapy. At physical examination, prolonged downward gaze to the right of about 2 minutes provoked paresis of abduction, slight ptosis, and restriction of elevation on the left side, corresponding to sixth nerve palsy and palsy of the superior branch of the third nerve on the left side. MRI showed a relapse of the macroadenoma with infiltration of the cavernous sinus on the left side. The patient underwent surgery then focal radiation (gamma-knife). The clinical course was favourable and at the follow-up examination six months later, no diplopia was reported.

Abducens Nerve Diseases↗

[Persistent visual problems thirty years after severe head trauma].

INTRODUCTION: Visual disturbances are common after severe head trauma. Some authors report 50 percent of these patients having damage to the visual system, ocular motor nerve palsies, or central eye movement disturbances. Visual disturbances influence prognosis and outcome of neurological rehabilitation, and, in most cases, diagnosis and treatment require interdisciplinary care. CASE REPORT: We report here a 50-year-old patient who suffered from severe head trauma at age 20. After coming out of a 4-week coma, he suffered visual disturbances such as blurred vision and diplopia. Visual acuity was 1.0 and the visual fields were intact. The symptoms remained unexplained for a long time. One year after the trauma, right trochlear palsy was diagnosed and surgical treatment was performed. However, the symptoms persisted, and one year later, a second operation was performed without changing the symptoms. During many years, prisms or refractive corrections were used to improve the visual disturbances, and finally, a psychiatric treatment was started. At age 40, the patient became presbyopic and his visual problems increased, especially for reading. When he was examined for the first time in our consultation, corrected visual acuity was 1.0 with a small hyperphoria of the right eye. During careful examination of the eye downgaze, a conjugate pure torsional nystagmus was observed, which disappeared in primary gaze position. CONCLUSION: Pure torsional nystagmus is difficult to diagnose, especially when it is provoked only by one gaze direction such as in our patient. As a sequel of the severe head trauma with brainstem contusion, this type of nystagmus is a rare form of central vestibular nystagmus, and may by modified by head rotation or suppressed by convergence. The "treatment" of the patient's blurred vision when reading was easy by ordering goggles with a near part placed near the primary gaze position and a 6 base down prismatic correction. Reading was then possible without provoking torsional nystagmus.

Coma↗

The role of the human dorsolateral prefrontal cortex in ocular motor behavior.

The dorsolateral prefrontal cortex (DLPFC) is involved in the preparation of saccadic eye movements. Lesion studies and functional magnetic resonance imaging (fMRI) studies suggest that the human DLPFC is located in area 46 of Brodmann. The DLPFC has direct connections with the main cortical ocular motor areas, that is with the frontal eye field (FEF) and the supplementary eye field (SEF) in the frontal lobe; with several (associative, attentional, and motor) areas in the posterior parietal cortex (PPC), including the parietal eye field (PEF); with the cingulate eye field in the anterior cingulate cortex; and directly downstream with the superior colliculus in the brainstem. Lesion and fMRI studies using the antisaccade paradigm have shown that the DLPFC is involved in the inhibition of unwanted reflexive saccades (triggered toward the target by the PEF), whereas the triggering of correct intentional antisaccades (made in the direction opposite to the target) may depend mainly upon the FEF. The DLPFC also controls short-term spatial working memory involved in memory-guided saccades, as shown by lesion and transcranial magnetic stimulation (TMS) studies. By contrast, medium-term spatial memory (after 25 s) may be controlled by the medial temporal cortex (MTC). Recently, TMS studies have suggested that the transmission of memorized information from the integrative parietal areas (PPC) to the MTC is performed via both an indirect pathway comprising the DLPFC (i.e., transmission in series) and a direct pathway bypassing the DLPFC (i.e., transmission in parallel). Furthermore, the DLPFC is involved in the preparation of predictive saccades (i.e., saccades made before the appearance of an expected target) and saccade sequences, and, therefore, also controls some aspects of temporal working memory. Lastly, the involvement of the DLPFC has recently been reported in tasks comprising a target selection or a directional decision to make for the forthcoming saccade. These different functions suggest that the DLPFC plays a major role in the decisional processes governing ocular motor behavior.

Animals↗

Verbal instructions and top-down saccade control.

Few studies have addressed the interaction between instruction content and saccadic eye movement control. To assess the impact of instructions on top-down control, we instructed 20 healthy volunteers to deliberately delay saccade triggering, to make inaccurate saccades or to redirect saccades--i.e. to glimpse towards and then immediately opposite to the target. Regular pro- and antisaccade tasks were used for comparison. Bottom-up visual input remained unchanged and was a gap paradigm for all instructions. In the inaccuracy and delay tasks, both latencies and accuracies were detrimentally impaired by either type of instruction and the variability of latency and accuracy was increased. The intersaccadic interval (ISI) required to correct erroneous antisaccades was shorter than the ISI for instructed direction changes in the redirection task. The word-by-word instruction content interferes with top-down saccade control. Top-down control is a time consuming process, which may override bottom-up processing only during a limited time period. It is questionable whether parallel processing is possible in top-down control, since the long ISI for instructed direction changes suggests sequential planning.

Acoustic Stimulation↗

Visual exploration behaviour during clock reading in Alzheimer's disease.

Eye movement behaviour during visual exploration of 24 patients with probable Alzheimer's disease and 24 age-matched controls was compared in a clock reading task. Controls were found to focus exploration on distinct areas at the end of each clock hand. The sum of these two areas of highest fixation density was defined as the informative region of interest (ROI). In Alzheimer's disease patients, visual exploration was less focused, with fewer fixations inside the ROI, and the time until the first fixation was inside the ROI was significantly delayed. Changes of fixation distribution correlated significantly with the ability to read the clock correctly, but did not correlate with dementia severity. In Alzheimer's disease patients, fixations were longer and saccade amplitudes were smaller. The altered visual exploration in Alzheimer's disease might be related to parietal dysfunction or to an imbalance between a degraded occipito-parietal and relatively preserved occipito-temporal visual network.

Aged↗

Cortical control of ocular saccades in humans: a model for motricity.

Our knowledge of the cortical control of saccadic eye movements (saccades) in humans has recently progressed mainly thanks to lesion and transcranial magnetic stimulation (TMS) studies, but also to functional imaging. It is now well-known that the frontal eye field is involved in the triggering of intentional saccades, the parietal eye field in that of reflexive saccades, the supplementary eye field (SEF) in the initiation of motor programs comprising saccades, the pre-SEF in learning of these programs, and the dorsolateral prefrontal cortex (DLPFC) in saccade inhibition, prediction and spatial working memory. Saccades may also be used as a convenient model of motricity to study general cognitive processes preparing movements, such as attention, spatial memory and motivation. Visuo-spatial attention appears to be controlled by a bilateral parieto-frontal network comprising different parts of the posterior parietal cortex and the frontal areas involved in saccade control, suggesting that visual attentional shifts and saccades are closely linked. Recently, our understanding of the cortical control of spatial memory has noticeably progressed by using the simple visuo-oculomotor model represented by the memory-guided saccade paradigm, in which a single saccade is made to the remembered position of a unique visual item presented a while before. TMS studies have determined that, after a brief stage of spatial integration in the posterior parietal cortex (inferior to 300 ms), short-term spatial memory (i.e. up to 15-20 s) is controlled by the DLPFC. Behavioral and lesion studies have shown that medium-term spatial memory (between 15-20 s and a few minutes) is specifically controlled by the parahippocampal cortex, before long-term memorization (i.e. after a few minutes) in the hippocampal formation. Lastly, it has been shown that the posterior part of the anterior cingulate cortex, called the cingulate eye field, is involved in motivation and the preparation of all intentional saccades, but not in reflexive saccades. These different but complementary study methods used in humans have thus contributed to a better understanding of both eye movement physiology and general cognitive processes preparing motricity as whole.

Cerebral Cortex↗

Decisional role of the dorsolateral prefrontal cortex in ocular motor behaviour.

Three patients with a unilateral cortical lesion affecting the dorsolateral prefrontal cortex (DLPFC), i.e. Brodmann area 46, were tested using different paradigms of reflexive saccades (gap and overlap tasks), intentional saccades (antisaccades, memory-guided and predictive saccades) and smooth pursuit movements. Visually guided saccades with gap and overlap, latency of correct antisaccades and memory-guided saccades and the gain of smooth pursuit were normal, compared with controls. These results confirm our anatomical data showing that the adjacent frontal eye field (FEF) was unimpaired in these patients. The specific pattern of abnormalities after a unilateral DLPFC lesion, compared with that of the FEF lesions previously reported, consists mainly of: (i) a bilateral increase in the percentage of errors in the antisaccade task (misdirected reflexive saccades); (ii) a bilateral increase in the variable error in amplitude, without significant decrease in the gain, in the memory-guided saccade task; and (iii) a bilateral decrease in the percentage of anticipatory saccades in the predictive task. Taken together, these results suggest that the DLPFC plays a crucial role in the decisional processes, preparing saccades by inhibiting unwanted reflexive saccades (inhibition), maintaining memorized information for ongoing intentional saccades (short-term spatial memory) or facilitating anticipatory saccades (prediction), depending upon current external environmental and internal circumstances.

Adult↗

Hemispheric asymmetry in visuospatial attention assessed with transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) was used to study visuospatial attention processing in ten healthy volunteers. In a forced choice recognition task the subjects were confronted with two symbols simultaneously presented during 120 ms at random positions, one in the left and the other in the right visual field. The subject had to identify the presented pattern out of four possible combinations and to press the corresponding response key within 2 s. Double-pulse TMS (dTMS) with a 100-ms interstimulus interval (ISI) and an intensity of 80% of the stimulator output (corresponding to 110-120% of the motor threshold) was applied by a non-focal coil over the right or left posterior parietal cortex (PPC, corresponding to P3/P4 of the international 10-20 system) at different time intervals after onset of the visual stimulus (starting at 120 ms, 270 ms and 520 ms). Double-pulse TMS over the right PPC starting at 270 ms led to a significant increase in percentage of errors in the contralateral, left visual field (median: 23% with TMS vs 13% without TMS, P=0.0025). TMS applied earlier or later showed no effect. Furthermore, no significant increase in contra- or ipsilateral percentage of errors was found when the left parietal cortex was stimulated with the same timing. These data indicate that: (1) parietal influence on visuospatial attention is mainly controlled by the right lobe since the same stimulation over the left parietal cortex had no significant effect, and (2) there is a vulnerable time window to disturb this cortical process, since dTMS had a significant effect on the percentage of errors in the contralateral visual hemifield only when applied 270 ms after visual stimulus presentation.

Adult↗

Effects of transcranial magnetic stimulation of the posterior parietal cortex on saccades and vergence.

Previous studies showed that transcranial magnetic stimulation (TMS) of the posterior parietal cortex (PPC) prolongs the latency of intentional saccades. We examined whether a similar effect exists for reflexive saccades and vergence. To elicit reflexive movements, a gap paradigm was used; lateral saccades and vergence along the median plane were interleaved. TMS was applied on the right PPC 80 ms after target onset. Blocks without TMS were performed and a control experiment with TMS over the primary motor cortex. The latter had no effect on the latency of any type of movements. In contrast, stimulation of the PPC increased the latency of both saccades and vergence, suggesting that the PPC is involved in the triggering of reflexive movements both in direction and in depth.

Adult↗

Functional organisation of the saccadic reference system processing extraretinal signals in humans.

In order to investigate the neuronal network involved in processing extraretinal signals, functional magnetic resonance imaging (fMRI) was applied to subjects performing the double step saccade paradigm. There, the calculation of the amplitude of the second saccade must rely on extraretinal signals of the first. When compared to a task where both saccades could be performed by means of retinal signals alone, a parieto-frontal cortical network was activated, including lateral intraparietal area, precuneus, insula, inferior frontal gyrus and anterior cingulum.

Adult↗

Double-pulse transcranial magnetic stimulation over the frontal eye field facilitates triggering of memory-guided saccades.

The study investigated the influence of double-pulse transcranial magnetic stimulation (dTMS) on memory-guided saccade triggering. Double pulses with interstimulus intervals (ISIs) of 35, 50, 65 or 80 ms were applied over the right frontal eye field (FEF) and as control over the occipital cortex. A significant dTMS effect was found exclusively for contralateral saccades; latency of memory-guided saccades was reduced after FEF stimulation with an ISI of 50 ms compared to latency without stimulation. This effect proved to be specific for the ISI of 50 ms over the FEF because control stimulation with the same ISI over the occipital cortex had no significant effect on latency of memory-guided saccades. The results of our study showed that, by using an appropriate ISI, dTMS is able to facilitate contralateral saccade triggering by stimulating the FEF. This suggests that TMS interferes specifically with saccade triggering mechanisms, probably by acting on presaccadic neurons of the FEF.

Adult↗

Beyond re-membering: phantom sensations of congenitally absent limbs.

Phantom limbs are traditionally conceptualized as the phenomenal persistence of a body part after deafferentation. Previous clinical observations of subjects with phantoms of congenitally absent limbs are not compatible with this view, but, in the absence of experimental work, the neural basis of such "aplasic phantoms" has remained enigmatic. In this paper, we report a series of behavioral, imaging, and neurophysiological experiments with a university-educated woman born without forearms and legs, who experiences vivid phantom sensations of all four limbs. Visuokinesthetic integration of tachistoscopically presented drawings of hands and feet indicated an intact somatic representation of these body parts. Functional magnetic resonance imaging of phantom hand movements showed no activation of primary sensorimotor areas, but of premotor and parietal cortex bilaterally. Movements of the existing upper arms produced activation expanding into the hand territories deprived of afferences and efferences. Transcranial magnetic stimulation of the sensorimotor cortex consistently elicited phantom sensations in the contralateral fingers and hand. In addition, premotor and parietal stimulation evoked similar phantom sensations, albeit in the absence of motor evoked potentials in the stump. These data indicate that body parts that have never been physically developed can be represented in sensory and motor cortical areas. Both genetic and epigenetic factors, such as the habitual observation of other people moving their limbs, may contribute to the conscious experience of aplasic phantoms.

Adult↗

Hemispheric asymmetry in cortical control of memory-guided saccades. A transcranial magnetic stimulation study.

To study the temporal organisation of memory-guided saccade control we used single-pulse transcranial magnetic stimulation (TMS) over the left posterior parietal (PPC) and prefrontal cortex (PFC) in eight healthy subjects. TMS was applied either following presentation of a visual target, i.e. 160, 260, and 360 ms after the flashed point, or during the period of memorisation, i.e. between 700 and 1500 ms, or finally 100 ms after extinguishing of the central fixation point (i.e. 2100 ms after the target presentation). Latency of memory-guided saccades and the percentage of error in amplitude (PEA) was measured and compared with results without stimulation.TMS over the left PPC 100 ms after the extinguishing of the central fixation point significantly increased memory-guided saccade latency bilaterally. Furthermore, stimulation over the left PFC had a significant effect on the PEA of contralateral memory-guided saccades when applied during the period of memorisation, i.e. between 700 and 1500 ms.In a previous study using identical methodology [13: Müri RM, Vermersch SI, Rivaud S, Gaymard B, Pierrot-Deseilligny C. Effects of single-pulse transcranial magnetic stimulation over the prefrontal and posterior parietal cortices during memory-guided saccades in humans. Journal of Neurophysiology 1996;76:2102-2106], we found that TMS over the right PPC increased the contralateral PEA when applied 260 ms after the flash, the effects on saccade latency after right PPC stimulation or on the PEA after right PFC stimulation being similar to those observed here. Taken together, these results show that (1) a hemispheric asymmetry in the preparation of memory-guided saccade amplitude during the early phase of sensorimotor integration exists, (2) memory-guided saccade triggering is controlled by PPC on both sides, and (3) PFC on both sides are involved in spatial working memory performance.

Adult↗

Saccadic eye movement disturbances in whiplash patients with persistent complaints.

In order to analyse the possible basis of subjective complaints following whiplash injury, horizontal eye movements were examined in subjects with persistent complaints ('symptomatic group') and subjects who had completely recovered ('recovered group'). The results for the symptomatic and recovered groups were compared with those for age-matched, healthy volunteers (control group). A battery of different saccade paradigms was employed: two were reflexive saccade tasks including a gap and an overlap task, and two were intentional saccade tasks consisting of an antisaccade and a memory-guided saccade task. In addition, the symptomatic and recovered groups also underwent psychiatric evaluation in a structured clinical interview, and all groups were assessed for emotional functioning using the Beck Depression Inventory (BDI). The recovered group did not differ significantly from the control group in saccade performance and emotional functioning. The symptomatic group showed dissociation of their performances of reflexive and intentional saccade tasks: performance in reflexive saccade tasks was normal, but in intentional saccade tasks the symptomatic group showed significantly impaired inhibition of unwanted reflexive saccades, impaired saccade triggering (i.e. increased latency) and a higher percentage error in amplitude in memory-guided saccades. Based on clinical interviews, no signs of major depression or dysthymia were found in any of the groups. Compared with the other two groups, the symptomatic group had significantly higher overall BDI scores, but these resulted from BDI dimensions that were non-specific to depression, viz. 'physiological manifestations' (e.g. fatigue, sleep disturbance) or 'performance difficulty' (e.g. work inhibition). In summary, in the symptomatic group the pattern of eye movement disturbances together with normal performance in reflexive saccade tasks and impaired performance in the intentional saccade tasks, especially impaired inhibitory function, suggests dysfunction of prefrontal and frontal cortical structures.

Adult↗

Eye-hand coordination in uni- and bimanual goal-oriented tasks.

Two different drawer tasks were investigated with the aim of assessing the role of eye movements in well-coordinated hand movements. In an unimanual step-tracking task, which had a predictive and an unpredictive movement, a two-way repeated-measures ANOVA showed a significant effect of prediction on the onset of grip-force (GF) rate (300+/-39 ms for the predictive condition versus 394+/-53 ms for the non-predictive condition, P<0.0001). Correlation coefficients, computed from the eye and the hand movements were low for the right and the left hand. The saccade was more coupled with the visual step change than with the action of the hand per se. In a second bimanual pull-and-pick task, the instruction was to pull a drawer with the left hand from a closed position to a LED-cued open position and then to grasp and reinsert a small peg in the drawer with the right hand. Correlation coefficients, computed from the latencies of saccades and of the leading left hand or of the right hand, were significant in four of five subjects. Intermanual correlations were significant in all five subjects. In conclusion, we found that the initial saccade in the unimanual task was best related with the visual step change, but was poorly correlated with the pulling/pushing hand. In the bimanual task, a moderate, but significant temporal coupling between the eyes and hand events was observed. This coupling was, however, less tight than that between both hands.

Acoustic Stimulation↗

Role of the prefrontal cortex in the control of express saccades. A transcranial magnetic stimulation study.

Single pulse transcranial magnet stimulation (TMS) was applied in five subjects during a saccadic gap task, i.e. with a temporal gap of 200 ms between the extinguishing of the central fixation point and the appearance of the lateral target. In all subjects, a significant increase of contralateral express saccades was found when TMS was applied over the dorsolateral prefrontal cortex (DPFC) at the end of the gap of 200 ms. Earlier stimulation over the DPFC during the gap had no significant effect. Furthermore, stimulation over the posterior parietal cortex with the same time intervals, and stimulation during a no gap task had no significant influence on express saccades. These results suggest that TMS is capable of interfering specifically with the functioning of the DPFC, probably by inhibition of this region. Possibly such stimulation of the DPFC reduces the inhibition by this region onto the superior colliculus, which results in a facilitation of express saccades.

Adult↗