The diagnostic value of the neurological examination in coma of unknown etiology.

BACKGROUND: Identifying the cause of non-traumatic coma in the emergency department is challenging. The clinical neurological examination is the most readily available tool to detect focal neurological deficits as indicators for cerebral causes of coma. Previously proposed clinical pathways have granted the interpretation of clinical findings a pivotal role in the diagnostic work-up. We aimed to identify the actual diagnostic reliability of the neurological examination with regard to identifying acute brain damage. METHODS: Eight hundred and fifty-three patients with coma of unknown etiology (CUE) were examined neurologically in the emergency department following a predefined routine. Coma-explaining pathologies were identified retrospectively and grouped into primary brain pathology with proof of acute brain damage and other causes without proof of acute structural pathology. Sensitivity, specificity and percentage of correct predictions of different examination protocols were calculated using contingency tables and binary logistic regression models. RESULTS: The full neurological examination was 74% sensitive and 60% specific to detect acute structural brain damage underlying CUE. Sensitivity and specificity were higher in non-sedated patients (87/61%) compared to sedated patients (64%/59%). A shortened four-item examination protocol focusing on pupils, gaze and pyramidal tract signs was only slightly less sensitive (67%) and more specific (65%). CONCLUSIONS: Due to limited diagnostic reliability of the physical examination, the absence of focal neurological signs in acutely comatose patients should not defer from a complete work-up including brain imaging. In an emergency, a concise neurological examination should thus serve as one part of a multimodal diagnostic approach to CUE.

[Coma in the emergency room]. / Koma in der Notaufnahme.

Coma of unknown origin (CUO) is a frequent unspecific emergency symptom associated with a high mortality. A fast diagnostic work-up is essential given the wide spectrum of underlying diagnoses that are made up of approximately 50% primary central nervous system (CNS) pathologies and approximately 50% extracerebral, almost exclusively internal medical causes. Despite the high mortality associated with this symptom, there are currently no generally accepted management guidelines for adult patients presenting with CUO. We propose an interdisciplinary standard operating procedure (SOP) for patients with acute CUO as has been established in our maximum care hospital. The SOP is triggered by simple triage criteria that are sufficient to identify CUO patients before arrival in hospital. The in-hospital response team is led by a neurologist. Collaboration with nursing staff, internal medicine, anesthesiology, neurosurgery and trauma surgery is organized along structured pathways that include standardized laboratory tests, including cerebrospinal fluid (CSF), toxicology, computed tomography (CT) and CT angiography imaging (CTA). Our data suggest that neurologists and internists need to be placed at the beginning of the diagnostic work-up. Imaging should not just be carried out depending on the clinical syndrome because sensitivity, specificity and inter-rater reliability of the latter are not sufficient and because in many cases, multiple pathologies can be detected that could each explain CUO alone. Clinical examination, imaging and laboratory testing should be regarded as components of an integrative diagnostic approach and the final aetiological classification should only be made after the diagnostic work-up is complete.

Imaging of autoimmune encephalitis--Relevance for clinical practice and hippocampal function.

The field of autoimmune encephalitides associated with antibodies targeting cell-surface antigens is rapidly expanding and new antibodies are discovered frequently. Typical clinical presentations include cognitive deficits, psychiatric symptoms, movement disorders and seizures and the majority of patients respond well to immunotherapy. Pathophysiological mechanisms and clinical features are increasingly recognized and indicate hippocampal dysfunction in most of these syndromes. Here, we review the neuroimaging characteristics of autoimmune encephalitides, including N-methyl-d-aspartate (NMDA) receptor, leucine-rich glioma inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2) encephalitis as well as more recently discovered and less frequent forms such as dipeptidyl-peptidase-like protein 6 (DPPX) or glycine receptor encephalitis. We summarize findings of routine magnetic resonance imaging (MRI) investigations as well as (18)F-fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography (PET) and single photon emission tomography (SPECT) imaging and relate these observations to clinical features and disease outcome. We furthermore review results of advanced imaging analyses such as diffusion tensor imaging, volumetric analyses and resting-state functional MRI. Finally, we discuss contributions of these neuroimaging observations to the understanding of the pathophysiology of autoimmune encephalitides.

Impairment of saccade adaptation in a patient with a focal thalamic lesion.

The frequent jumps of the eyeballs-called saccades-imply the need for a constant correction of motor errors. If systematic errors are detected in saccade landing, the saccade amplitude adapts to compensate for the error. In the laboratory, saccade adaptation can be studied by displacing the saccade target. Functional selectivity of adaptation for different saccade types suggests that adaptation occurs at multiple sites in the oculomotor system. Saccade motor learning might be the result of a comparison between a prediction of the saccade landing position and its actual postsaccadic location. To investigate whether a thalamic feedback pathway might carry such a prediction signal, we studied a patient with a lesion in the posterior ventrolateral thalamic nucleus. Saccade adaptation was tested for reactive saccades, which are performed to suddenly appearing targets, and for scanning saccades, which are performed to stationary targets. For reactive saccades, we found a clear impairment in adaptation retention ipsilateral to the lesioned side and a larger-than-normal adaptation on the contralesional side. For scanning saccades, adaptation was intact on both sides and not different from the control group. Our results provide the first lesion evidence that adaptation of reactive and scanning saccades relies on distinct feedback pathways from cerebellum to cortex. They further demonstrate that saccade adaptation in humans is not restricted to the cerebellum but also involves cortical areas. The paradoxically strong adaptation for outward target steps can be explained by stronger reliance on visual targeting errors when prediction error signaling is impaired.

Altered basal ganglia functional connectivity in multiple sclerosis patients with fatigue.

BACKGROUND: Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis, but its pathophysiological mechanisms are poorly understood. It is in particular unclear whether and how fatigue relates to structural and functional brain changes. OBJECTIVE: We aimed to analyse the association of fatigue severity with basal ganglia functional connectivity, basal ganglia volumes, white matter integrity and grey matter density. METHODS: In 44 patients with relapsing-remitting multiple sclerosis and 20 age- and gender-matched healthy controls, resting-state fMRI, diffusion tensor imaging and voxel-based morphometry was performed. RESULTS: In comparison with healthy controls, patients showed alteration of grey matter density, white matter integrity, basal ganglia volumes and basal ganglia functional connectivity. No association of fatigue severity with grey matter density, white matter integrity and basal ganglia volumes was observed within patients. In contrast, fatigue severity was negatively correlated with functional connectivity of basal ganglia nuclei with medial prefrontal cortex, precuneus and posterior cingulate cortex in patients. Furthermore, fatigue severity was positively correlated with functional connectivity between caudate nucleus and motor cortex. CONCLUSION: Fatigue is associated with distinct alterations of basal ganglia functional connectivity independent of overall disability. The pattern of connectivity changes suggests that disruption of motor and non-motor basal ganglia functions, including motivation and reward processing, contributes to fatigue pathophysiology in multiple sclerosis.

Outcome prediction in patients after cardiac arrest: a simplified method for determination of gray-white matter ratio in cranial computed tomography.

PURPOSE: Out-of-hospital cardiac arrest is a frequent cause of death in Europe. Hypoxic ischemic encephalopathy (HIE) often develops in initial survivors, and the question of treatment limitation arises in severely affected patients. To establish a poor prognosis with a high level of certainty, the use of a combination of prognostic parameters such as neurological examination, somatosensory evoked potentials, and neuron-specific enolase is common practice. A few recent studies suggest that gray-white matter ratio (GWR) determined from cranial computed tomography (CT) scans is an additional reliable predictor of poor prognosis. The standard GWR determination method involves measurements of 16 different regions of interest (ROIs). We tested whether a simplified method to obtain GWR has equivalent reliability for poor outcome prediction. MATERIALS AND METHODS: We retrospectively analyzed 98 patients after cardiac arrest who had been treated with hypothermia. CT scans were obtained within the first 7 days after cardiac arrest. Neurological outcome was determined at intensive care unit discharge. Four different methods to obtain GWR were compared in a receiver-operating characteristic curve analysis with respect to their prognostic value for poor outcome prediction. RESULTS: The simplest method using only four ROIs (putamen and internal capsule bilaterally) had the same prognostic value compared with the standard method using 16 ROIs. The simplified GWR predicted poor outcome with a sensitivity of 44 % at 100 % specificity. CONCLUSION: Our results indicate that for poor outcome prediction in survivors of cardiac arrest, a simplified GWR determination is feasible and has the same reliability as the complex standard procedure.

Regional cerebral oxygen saturation after cardiac arrest in 60 patients--a prospective outcome study.

INTRODUCTION: Non-invasive near-infrared spectroscopy (NIRS) offers the possibility to determine regional cerebral oxygen saturation (rSO2) in patients with cardiac arrest. Limited data from recent studies indicate a potential for early prediction of neurological outcome. METHODS: Sixty cardiac arrest patients were prospectively enrolled, 22 in-hospital cardiac arrest (IHCA) and 38 out-of-hospital cardiac arrest (OHCA) patients respectively. NIRS of frontal brain was started after return of spontaneous circulation (ROSC) during admission to ICU and was continued until normothermia. Outcome was determined at ICU discharge by the Pittsburgh Cerebral Performance Category (CPC) and 6 months after cardiac arrest. RESULTS: A good outcome (CPC 1-2) was achieved in 23 (38%) patients, while 37 (62%) had a poor outcome (CPC 3-5). Patients with good outcome had significantly higher rSO2 levels (CPC 1-2: rSO2 68%; CPC 3-5: rSO2 58%; p<0.01). For good and poor outcome median rSO2 within the first 24h period was 66% and 59% respectively and for the following 16h period 68% and 59% (p<0.01). Outcome prediction by area of rSO2 below a critical threshold of rsO2=50% within the first 40h yielded 70% specificity and 86% sensitivity for poor outcome. CONCLUSION: On average, rSO2 within the first 40h after ROSC is significantly lower in patients with poor outcome, but rSO2 ranges largely overlap between outcome groups. Our data indicate limited potential for prediction of poor outcome by frontal brain rSO2 measurements.

[Neurological chief complaints in an emergency room]. / Neurologische Leitsymptome in einer Notaufnahme.

Neurological chief complaints often lead patients into the emergency room. In order to establish standard emergency workups it is important to know the frequency of neurological chief complaints. Therefore, we performed a retrospective study on 4,132 consecutive neurological patients in the emergency room over a 1-year period. The most frequent chief complaint was headache (20%) followed by motor deficit (13%), vertigo (12%) and epileptic seizure (11%). In conclusion, the neurological workup in the emergency room can be optimized by establishing clinical decision-making rules for the four most frequent chief complaints.

[Fragile X-associated tremor/ataxia syndrome]. / Fragiles X-assoziiertes Tremor-/Ataxie-Syndrom.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently characterized adult onset neurodegenerative disorder affecting both male and female (male>female) carriers of premutation CGG repeat expansions of the FMR1 gene. Onset typically occurs after the age of 50 years with a lifetime risk of FXTAS in males of about 1 in 3,000-6,000. Core features include progressive gait ataxia and cerebellar tremor with associated features of cognitive deficits, peripheral neuropathy and dysautonomia. The diagnosis of FXTAS is established based on clinical presentation, cerebral imaging and genetic testing. Due to the still low level of awareness of FXTAS and its variable clinical picture FXTAS is substantially underdiagnosed. However, confirming the diagnosis is essential for genetic counseling of the patients as the offspring are at risk for fragile X syndrome, premature ovarian insufficiency (POI) or FXTAS. Furthermore, many features of FXTAS can be treated symptomatically.

Inhibition of orienting during a memory-guided saccade task shows a Mexican-hat distribution.

Recent behavioral studies in monkeys and humans have shown that holding an item in spatial working memory may lead to sustained and spatially selective prolongation of reaction times (RTs) to visual stimuli presented during the memory delay. In order to resolve the seeming contradiction between these findings and current theories on the interaction of working memory and attentional orienting, it has been hypothesized that memory-dependent modulation of orienting may be the net effect of superposed facilitatory and inhibitory mechanisms. Their relative strength during the memory delay may determine whether RTs to visual stimuli presented during the memory delay are shortened or prolonged. Here, we expand on this hypothesis by investigating the spatial distribution of memory-dependent inhibition with behavioral data from normal human subjects. The experiment consisted of a combination of an oculomotor spatial working memory task (memory-guided saccade task, 6-s delay) and a visual discrimination task (performed 1500, 2500, or 3500 ms after presentation of the memory cue). RTs to discrimination stimuli were analyzed as a function of memory-guided saccade amplitude. By fitting polynomial approximations to our data we show that the spatial distribution of memory-dependent inhibition of orienting significantly differs from a monotonic gradient across the visual field. Instead, we demonstrate the existence of a central inhibitory peak surrounded by a facilitatory annulus, forming a transient "inverted Mexican hat" profile, which mirror-images findings from recent studies on the spatial distribution of attention. These findings are consistent with the hypothesis of a highly flexible modulation of orienting in which both the signs and spatial distribution of memory-dependent bias signals are adapted to behavioral demands.

Perisaccadic mislocalization without saccadic eye movements.

Despite frequent saccadic gaze shifts we perceive the surrounding visual world as stable. It has been proposed that the brain uses extraretinal eye position signals to cancel out saccade-induced retinal image motion. Nevertheless, stimuli flashed briefly around the onset of a saccade are grossly mislocalized, resulting in a shift and, under certain conditions, an additional compression of visual space. Perisaccadic mislocalization has been related to a spatio-temporal misalignment of an extraretinal eye position signal with the corresponding saccade. Here, we investigated perceptual mislocalization of human observers both in saccade and fixation conditions. In the latter conditions, the retinal stimulation during saccadic eye movements was simulated by a fast saccade-like shift of the stimulus display. We show that the spatio-temporal pattern of both the shift and compression components of perceptual mislocalization can be surprisingly similar before real and simulated saccades. Our findings suggest that the full pattern of perisaccadic mislocalization can also occur in conditions which are unlikely to involve changes of an extraretinal eye position signal. Instead, we suggest that, under the conditions of our experiments, the arising difficulty to establish a stable percept of a briefly flashed stimulus within a given visual reference frame yields mislocalizations before fast retinal image motion. The availability of visual references appears to exert a major influence on the relative contributions of shift and compression components to mislocalization across the visual field.

Neural substrate of antisaccades: role of subcortical structures.

BACKGROUND: Experimental and clinical studies suggest that the dorsolateral prefrontal cortex (DLPFC) and the superior colliculus (SC) are crucial for the cancellation of reflexive eye movements toward distracting stimuli. However, the contribution of subcortical structures remains unknown. The basal ganglia provide serial tonic inhibitory connections between the DLPFC and the SC, and could therefore be involved in preventing the triggering of unnecessary saccades. The DLPFC could also exert its inhibitory effect on the SC through direct prefronto-tectal pathways that travel in the internal capsule (IC). Since thalamic dysfunction may be responsible for reduced DLPFC activation, it may be hypothesized that the thalamus could also participate in saccadic inhibition. METHODS: The authors recorded reflexive saccade triggering (prosaccade task) and inhibition (antisaccade task) in 29 patients with a single lesion affecting the striatum, the thalamus, or the IC, and compared these results to control subjects. RESULTS: A normal error rate in the antisaccade task was found in patients with 1) a basal ganglia lesion, 2) a thalamic lesion, or 3) a lesion restricted to the posterior half of the posterior limb of the IC. An increased error rate in the antisaccade task was found in patients with a lesion affecting the anterior limb, the genu, or the anterior half of the posterior limb of the IC. CONCLUSION: These results suggest that neither the basal ganglia nor the thalamus plays a major role in reflexive saccade suppression, but support the hypothesis of a direct DLPFC inhibitory control of saccade triggering on the SC.

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.

The parieto-collicular pathway: anatomical location and contribution to saccade generation.

The monkey lateral intraparietal area (LIP), involved in reflexive shifts of visual attention, has two main oculomotor outputs: towards frontal oculomotor areas and towards the superior colliculus. Recent studies suggest that these two outputs do not carry similar information. Direct LIP-collicular neurons would convey visual signals providing the oculomotor system with on-line visuo-spatial information. Parietal visuo-spatial information regarding internal stimuli would access the brainstem oculomotor circuitry through a parieto-frontal network. Consequently, an interruption of parieto-tectal neurons should affect reflexive saccades towards unpredictable targets and have little or no effect on saccades towards predictable or memorised stimuli. In order to test this hypothesis in humans, we have determined in rhesus monkeys the location of LIP-tectal fibres in the region of the internal capsule, and found that these neurons travel in the most posterior region of the posterior limb of the internal capsule. We have then tested, in seven patients with a small lesion involving this region, several oculomotor paradigms designed to determine the influence of spatial predictability on saccade accuracy and the ability to withhold reflexive saccades. In all patients, saccade accuracy was affected in unpredictable conditions but was normal when target location could be predicted or memorised. Reflexive saccade inhibition was affected only in the three patients in whom the capsular lesion had the most anterior extent. These results therefore support in humans the hypothesis that parieto-tectal neurons (i) transmit an on-line signal that is used by the oculomotor system for reflexive saccade triggering, (ii) are not crucial for the computation of internally guided saccades and (iii) are not crucial for reflexive saccade inhibition.

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.

Eyelid tremor in a patient with a unilateral paramedian thalamic lesion.

A patient with a circumscribed infarction of the right paramedian thalamus developed a tremor of both eyelids on voluntary eye closure. Co-registration of the magnetic resonance image to a stereotactic atlas of the human thalamus revealed that the lesion was confined to a small subgroup of paramedian nuclei, including the parvocellular part of the mediodorsal nucleus. It is concluded that this region provides inhibitory input to cortical and/or subcortical regions controlling eyelid movements. Voluntary eye closure may involve direct cortico-nuclear connections and indirect pathways through the paramedian thalamus, most probably through the mediodorsal nucleus.

Effects of cortical lesions on saccadic: eye movements in humans.

Our knowledge of the cortical control of saccadic eye movements (saccades) in humans has recently progressed mainly because of lesion and transcranial magnetic stimulation (TMS) studies, but also because of functional imaging. It is now well known that the frontal eye field is involved in the control 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 the 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 such as motivation and spatial memory. Thus, 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. Recently, our understanding of the cortical control of spatial memory has noticeably progressed by using the simple visuo-oculomotor model represented by the memory-guide saccade paradigm, in which a single saccade is made to the remembered position of a unique visual item presented a while before. Transcranial magnetic stimulation 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 seconds) is controlled by the DLPFC. Behavioral and lesion studies have shown that medium-term spatial memory (between 15 and 20 seconds 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. 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.

Involvement of the cerebellar thalamus in human saccade adaptation.

Saccade adaptation can be experimentally induced by systematically displacing a visual cue during a targeting saccade. Non-human primate studies have highlighted the crucial role of the cerebellum for saccade adaptation, but its neural substrates in humans are poorly understood. Recent physiological experiments suggest that, in addition to cerebellar structures, cortical areas may be involved as well. We have therefore hypothesized that saccade adaptation may rely on a cerebello-cerebral network, in which the cerebellar thalamus may link cerebellar and cerebral structures. To test this hypothesis, we studied saccade adaptation in a group of four patients with a thalamic lesion, with (n = 2) or without (n = 2) involvement of the cerebellar thalamus. Compared to healthy subjects, saccade adaptation was reduced in patients with associated cerebellar syndrome, but normal in patients without cerebellar syndrome. These results are consistent with the hypothesis that cerebello-thalamic pathways contribute to saccade adaptation in humans and suggest that the thalamus relays adaptation-related information from the cerebellum to cerebral cortical oculomotor areas.

In vivo assessment of human visual system connectivity with transcranial electrical stimulation during functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) was used to investigate local and distant cerebral activation induced by transcranial electrical stimulation in order to noninvasively map functional connectivity in the human visual system. Stimulation with lateromedially directed currents and the anode 4.5 cm dorsally to the inion over the right visual cortex induced phosphenes extending into the contralateral lower quadrant of the visual field. fMRI showed a focal hemodynamic response underneath the anode in extrastriate cortex and distant coactivation in subcortical (lateral geniculate nucleus), cortical visual (striate and extrastriate), and visuomotor areas (frontal and supplementary eye fields). This pattern of activation resembles a network of presumably interconnected visual and visuomotor areas. Analysis of activation sites supplies new information about cerebral correlates of phosphenes and shows that the cortical region underneath the cranial stimulation site is not necessarily the origin of behavioral and/or perceptual effects of transcranial stimulation. We conclude that combining transcranial electrical stimulation of neural tissue with simultaneous fMRI offers the possibility to study noninvasively cerebral connectivity in the human brain.

Behavioural relevance modulates access to spatial working memory in humans.

Neurophysiological studies in monkeys suggest selective representation of behaviourally relevant information in working memory. So far, no behavioural evidence for this has been reported for humans. Here, we investigated the role of behavioural relevance for access to human visuospatial working memory by using delayed oculomotor response tasks. Subjects were presented two successive visual cues in different and unpredictable locations while fixating on a central fixation point. After a delay, an unpredictable auditory signal (one beep or two beeps) sounded and the central fixation point was turned off, initiating the oculomotor response (i.e. memory-guided saccade) phase. Two groups of 10 subjects each were studied in two conditions: in the 'relevant' condition, subjects were instructed to memorize both visual cues and to move the eyes to the remembered position of the first cue (one beep) or the second cue (two beeps). The same stimuli were used in the 'irrelevant' condition, but subjects were instructed to memorize and move the eyes to the position of the first cue only, regardless of the second cue and the auditory signal. In the 'relevant' condition, we found a significant increase in errors of memory-guided saccades to the first cue, when the second cue was located between central fixation point and first cue. This spatially selective interference effect disappeared in the 'irrelevant' condition, despite identical stimuli. On a behavioural level, these results show for the first time the significance of behavioural relevance for access to human spatial working memory. These findings complement recent single-neuron studies in monkeys, showing that the neuronal substrates of working memory selectively represent behaviourally relevant perceptual information.