A frontoparietal network for volitional control of gaze following.

Gaze following is a major element of non-verbal communication and important for successful social interactions. Human gaze following is a fast and almost reflex-like behaviour, yet it can be volitionally controlled and suppressed to some extent if inappropriate or unnecessary, given the social context. In order to identify the neural basis of the cognitive control of gaze following, we carried out an event-related fMRI experiment, in which human subjects' eye movements were tracked while they were exposed to gaze cues in two distinct contexts: A baseline gaze following condition in which subjects were instructed to use gaze cues to shift their attention to a gazed-at spatial target and a control condition in which the subjects were required to ignore the gaze cue and instead to shift their attention to a distinct spatial target to be selected based on a colour mapping rule, requiring the suppression of gaze following. We could identify a suppression-related blood-oxygen-level-dependent (BOLD) response in a frontoparietal network comprising dorsolateral prefrontal cortex (dlPFC), orbitofrontal cortex (OFC), the anterior insula, precuneus, and posterior parietal cortex (PPC). These findings suggest that overexcitation of frontoparietal circuits in turn suppressing the gaze following patch might be a potential cause of gaze following deficits in clinical populations.

Frontal, Parietal, and Temporal Brain Areas Are Differentially Activated When Disambiguating Potential Objects of Joint Attention.

Humans establish joint attention with others by following the other's gaze. Previous work has suggested that a cortical patch (gaze-following patch, GFP) close to the posterior superior temporal sulcus (pSTS) may serve as a link between the extraction of the other's gaze direction and the resulting shifts of attention, mediated by human lateral intraparietal area (hLIP). However, it is not clear how the brain copes with situations in which information on gaze direction alone is insufficient to identify the target object because more than one may lie along the gaze vector. In this fMRI study, we tested human subjects on a paradigm that allowed the identification of a target object based on the integration of the other's gaze direction and information provided by an auditory cue on the relevant object category. Whereas the GFP activity turned out to be fully determined by the use of gaze direction, activity in hLIP reflected the total information needed to pinpoint the target. Moreover, in an exploratory analysis, we found that a region in the inferior frontal junction (IFJ) was sensitive to the total information on the target. An examination of the BOLD time courses in the three identified areas suggests functionally complementary roles. Although the GFP seems to primarily process directional information stemming from the other's gaze, the IFJ may help to analyze the scene when gaze direction and auditory information are not sufficient to pinpoint the target. Finally, hLIP integrates both streams of information to shift attention to distinct spatial locations.

Eye position information is used to compensate the consequences of ocular torsion on V1 receptive fields.

It is commonly held that the receptive fields (RFs) of neurons in primary visual cortex (V1) are fixed relative to the retina. Hence, V1 should be unable to distinguish between retinal image shifts due to object motion and image shifts resulting from ego motion. Here we show that, in contrast to this belief, a particular class of neurons in V1 of non-human primates have RFs that are actually head centred, despite intervening eye movements. They use eye position information to shift their RFs location and to change their orientation tuning on the retina so as to fully compensate for the retinal consequences of a particular type of reflexive eye movements, ocular counter-roll, an eye rotation around the line of sight partially counterpoising head tilt. In other words, V1 uses eye position information to resolve the ambiguity if retinal image tilt is the result of the tilting of an object or of the ocular counter-roll.

Parietal blood oxygenation level-dependent response evoked by covert visual search reflects set-size effect in monkeys.

Distinguishing a target from distractors during visual search is crucial for goal-directed behaviour. The more distractors that are presented with the target, the larger is the subject's error rate. This observation defines the set-size effect in visual search. Neurons in areas related to attention and eye movements, like the lateral intraparietal area (LIP) and frontal eye field (FEF), diminish their firing rates when the number of distractors increases, in line with the behavioural set-size effect. Furthermore, human imaging studies that have tried to delineate cortical areas modulating their blood oxygenation level-dependent (BOLD) response with set size have yielded contradictory results. In order to test whether BOLD imaging of the rhesus monkey cortex yields results consistent with the electrophysiological findings and, moreover, to clarify if additional other cortical regions beyond the two hitherto implicated are involved in this process, we studied monkeys while performing a covert visual search task. When varying the number of distractors in the search task, we observed a monotonic increase in error rates when search time was kept constant as was expected if monkeys resorted to a serial search strategy. Visual search consistently evoked robust BOLD activity in the monkey FEF and a region in the intraparietal sulcus in its lateral and middle part, probably involving area LIP. Whereas the BOLD response in the FEF did not depend on set size, the LIP signal increased in parallel with set size. These results demonstrate the virtue of BOLD imaging in monkeys when trying to delineate cortical areas underlying a cognitive process like visual search. However, they also demonstrate the caution needed when inferring neural activity from BOLD activity.

The dependencies of fronto-parietal BOLD responses evoked by covert visual search suggest eye-centred coding.

Visual scenes explored covertly are initially represented in a retinal frame of reference (FOR). On the other hand, 'later' stages of the cortical network allocating spatial attention most probably use non-retinal or non-eye-centred representations as they may ease the integration of different sensory modalities for the formation of supramodal representations of space. We tested if the cortical areas involved in shifting covert attention are based on eye-centred or non-eye-centred coding by using functional magnetic resonance imaging. Subjects were scanned while detecting a target item (a regularly oriented 'L') amidst a set of distractors (rotated 'L's). The array was centred either 5° right or left of the fixation point, independent of eye-gaze orientation, the latter varied in three steps: straight relative to the head, 10° left or 10° right. A quantitative comparison of the blood-oxygen-level-dependent (BOLD) responses for the three eye-gaze orientations revealed stronger BOLD responses in the right intraparietal sulcus (IPS) and the right frontal eye field (FEF) for search in the contralateral (i.e. left) eye-centred space, independent of whether the array was located in the right or left head-centred hemispace. The left IPS showed the reverse pattern, i.e. an activation by search in the right eye-centred hemispace. In other words, the IPS and the right FEF, members of the cortical network underlying covert search, operate in an eye-centred FOR.

Non-human primates exhibit disconjugate ocular counterroll to head roll tilts.

To investigate the effect of head roll tilt on the binocular coordination of ocular counterroll in non-human primates, we measured binocular ocular counterroll in two rhesus monkeys fixating a straight ahead target, while adopting different head roll tilt positions. We used two infrared cameras to take snapshots of the left and the right eye in order to measure the resulting ocular counterroll responses. The horizontal and vertical components of the position of one of the two eyes where measured using an implanted 2D-search coil in one monkey and video-based eye tracking in the second one. We consistently observed disconjugate ocular counterroll responses to static head roll in both monkeys. Invariably, the eye positioned further away from ground level by roll tilting the head always exhibited larger ocular counterroll than the other eye. The pattern of disconjugacy of the ocular counterroll responses exhibited by rhesus monkey parallels the one described for humans. The correspondence between the two species suggests that monkeys may serve as useful models in studies of the neuronal underpinnings of tilt-induced ocular counterroll and the perceptual compensation of uncompensated retinal image tilt.

Normal spatial attention but impaired saccades and visual motion perception after lesions of the monkey cerebellum.

Lesions of the cerebellum produce deficits in movement and motor learning. Saccadic dysmetria, for example, is caused by lesions of the posterior cerebellar vermis. Monkeys and patients with such lesions are unable to modify the amplitude of saccades. Some have suggested that the effects on eye movements might reflect a more global cognitive deficit caused by the cerebellar lesion. We tested that idea by studying the effects of vermis lesions on attention as well as saccadic eye movements, visual motion perception, and luminance change detection. Lesions in posterior vermis of four monkeys caused the known deficits in saccadic control. Attention tested by examination of acuity threshold changes induced by prior cueing of the location of the targets remained normal after vermis lesions. Luminance change detection was also unaffected by the lesions. In one case, after a lesion restricted to lobulus VIII, the animal had impaired visual motion perception.

Transient change in GABA(A) receptor subunit mRNA expression in Lurcher cerebellar nuclei during Purkinje cell degeneration.

BACKGROUND: Lurcher mice suffer from a complete Purkinje cell (PC) loss in the first four postnatal weeks. Parallel to this degeneration, GABAergic synapses in the deep cerebellar nuclei (DCN), the major recipient of the inhibitory PC projection, increase synaptic conductance. Here, we further investigated this phenomenon, using real-time RT-PCR to assess GABAA receptor subunit gene expression during PC degeneration. RESULTS: We observed a specific reduction in gamma2 subunit gene expression, while alpha1-5, beta1-2, gamma1,3 and delta subunits were unaffected. We made two further specific findings. First, the difference in gene expression was shown in tissue from DCN only. Neither the hippocampus nor coronal sections through the forebrain showed such effects. Furthermore, the involvement of different levels of corticosterone, a possible humeral trigger for differences in gene expression, could be excluded. Second, like the known potentiation of GABAergic synapses, the gamma2 down-regulation was present only after the onset of degeneration at p14. The difference in gamma2 mRNA expression, however, appeared transient, since it was no longer detectable in adult Lurcher mice. CONCLUSION: In conclusion, the down-regulation of gamma2 subunits may be related to differences in synaptic efficacy and, as such, may reflect the initial phase of adaptive responses of DCN tissue to massive GABAergic deafferentation. Its transient course, however, does not support the idea that modulations in GABAergic transmission are at the basis of the well-known DCN-based functional benefit of Lurcher mice present throughout their life.

Lurcher mice exhibit potentiation of GABA(A)-receptor-mediated conductance in cerebellar nuclei neurons in close temporal relationship to Purkinje cell death.

In heterozygous Lurcher mice (Lc/+), the Purkinje cells (PCs) degenerate almost totally during postnatal development. On the other hand, their projection target, the deep cerebellar nuclei (DCN), shows few signs of degeneration and seems to play an important role in maintaining a residual cerebellar function in Lc/+. We asked whether the DCN in Lc/+ develop cellular adaptations allowing them to cope with the loss of GABAergic PC input. Using whole-cell patch-clamp recordings, we measured inhibitory postsynaptic currents from DCN of Lc/+ and wild-type mice (WT). In experiments on phenotypically striking Lc/+ studied well after the onset of the PC degeneration, we found enlarged average synaptic conductances (g(syn)) compared with WT. We next investigated postnatal mice before and after the onset of PC death. In younger animals

Optimizing visual motion perception during eye movements.

We usually perceive a stationary, stable world and we are able to correctly estimate the direction of heading from optic flow despite coherent visual motion induced by eye movements. This astonishing example of perceptual invariance results from a comparison of visual information with internal reference signals predicting the visual consequences of an eye movement. Here we demonstrate that the reference signal predicting the consequences of smooth-pursuit eye movements is continuously calibrated on the basis of direction-selective interactions between the pursuit motor command and the rotational flow induced by the eye movement, thereby minimizing imperfections of the reference signal and guaranteeing an ecologically optimal interpretation of visual motion.

Neuronal responses from beyond the classic receptive field in V1 of alert monkeys.

Responses of primary visual cortex (V1) neurons to stimuli inside the classic receptive field (CRF) can be modulated by stimuli outside the CRF. We recently reported that responses of most V1 neurons to a line in the CRF center are inhibited by large surround-stimuli and that this modulation is stimulus selective. Here we report that a significant proportion of V1 neurons in alert monkeys respond directly to stimuli outside the CRF with very long latency and much reduced selectivity. When surround stimuli are presented alone, three response patterns can be distinguished in 153 single- or multiunits tested: (1) 31.4% have no significant response; (2) 50.3% show excitatory responses that are significantly higher than spontaneous activity. The average latency of these responses is about 145 ms, 2-3 times longer than center responses; (3) 18.3% show suppressed spontaneous activity after stimulus onset. The direct surround responses are found to be only weakly selective for the orientation of contextual lines, and not selective for other contextual patterns tested. While the outburst of responses to stimuli within the CRF is not affected by reducing stimulus duration from 500 ms to 50 ms, late excitatory surround responses are virtually eliminated. We propose that the late excitatory surround responses to extra-CRF stimulation alone are the reflection of feedback from higher cortical areas and may contribute to reduced contextual inhibition of cells in V1. This could play a role in figure-ground segregation.

Two types of neurons in the rat cerebellar nuclei as distinguished by membrane potentials and intracellular fillings.

Classically, three classes of neurons in the cerebellar nuclei (CN), defined by different projection targets and content of transmitters, have been distinguished. However, evidence for different types of neurons based on different intrinsic properties is lacking. The present study reports two types of neurons defined mainly by their intrinsic properties, as determined by whole-cell patch recordings. The majority of cells (type I, n = 63) showed cyclic burst firing whereas a small subset (type II, n = 7) did not. Burst firing was used to distinguish the two types of neurons because, as it turned out, pharmacological interference could not be used to convert the non-bursting cells to bursting ones. Some of the membrane potentials exclusively present in type I neurons, such as sodium and calcium plateau potentials, low-threshold calcium spikes, and a slow calcium-dependent afterhyperpolarization, were found to contribute to the generation of burst firing. Other membrane potentials of type I neurons were not obviously related to the generation of bursts. These were 1) the lower amplitude and width of the action potential during spontaneous activity, 2) a sequence of afterhyperpolarization-afterdepolarization-afterhyperpolarization following each spike, and 3) the high spontaneous firing rate. In contrast, type II neurons lacked slow plateau potentials and low threshold spikes. Their action potentials showed higher amplitude and width and were followed by a single deep afterhyperpolarization. Furthermore, they showed a lower firing rate at rest. In both types of neurons, a delayed inward rectification was present. Neurons filled with neurobiotin revealed that the sizes of the somata and dendritic fields of type I neurons comprised the whole range known from Golgi studies, whereas those of the few type II neurons recovered were found to be in the lowest range. In view of their size and scarcity, we propose that type II neurons may correspond to CN interneurons.

Cortical substrates of perceptual stability during eye movements.

We are usually unaware of retinal image motion resulting from our own movement. For instance, during slow-tracking eye movements, the world around us remains perceptually stable despite the retinal image slip induced by the eye movement. This example of perceptual invariance is achieved by subtracting an internal reference signal, reflecting the eye movement, from the retinal motion signal. If the two cancel each other, visual structures, which do not move, will also be perceived as nonmoving. If, however, the reference signal is too small or too large, a false eye-movement-induced motion of the external world will be perceived. We have exploited our ability to manipulate the size of the reference signal in an attempt to reveal the structures in visual cortex, encoding the perception of self-induced visual motion rather than the retinal motion signal. Using EEG and lately also MEG recordings in human subjects and single-unit recordings in monkeys, we have been able to show that our ability to perceive the world as stationary despite eye-movement-induced retinal image slip is based on "late" parts of the cortical hierarchy of motion processing, sparing the early stages up to cortical area MT and, among others, involving cortex at the junction between the parietal and temporal lobes close to the parieto-insular-vestibular cortex. Lesions of this network in humans render the visual system unable to compensate for the visual consequences of eye movements, giving rise to severe dizziness, whenever the eyes move smoothly.

Body experience and mental representation of body image in patients with haematological malignancies and cancer as assessed with the Body Grid.

The domain of body image plays a central role in the quality of life of patients with haematological malignancies and metastasized cancer, since the disease itself as well as the enrolled therapies interfere with psychological and bodily well-being. We approached this highly subjective field by using the repertory grid technique and hypothesized that patients would display a restricted body image, focusing on functional aspects of the body. In all, 55 in-patients (27 men, 28 women, M age = 45.7 yrs, N = 46 with haematological malignancies, N = 9 with metastasized cancer), at the time of initial diagnosis, were included in the study and assessed with the Body Grid, an instrument specifically designed by us for the exploration of body image. The data were analysed by principal component analysis (PCA) and construct categorization. Further, 42 chronic tinnitus sufferers (20 male, 22 female, M age = 46.5 yrs) served as a comparison group. Based on the constructs elicited, six construct categories were formulated in the sense of a first attempt of a hierarchical model (emotion, control, activity, strength, function, appearance). The central constructs (373 construct pairs) were assigned to these categories by three inter-raters. The categories appeared in the following order of frequency: function (27.1%), emotion (20.4%), strength (20.1%), activity (15%), control (10.2%) and appearance (7.2%). PCA indicated that the patients mainly demonstrated a restricted view of their body. In the tinnitus group, the most frequent category proved to be activity (21.3%), closely followed by function (21.1%) and control (20.9%). The body image was also restricted (PCA). The restriction of body image, together with the specific construct choice, seen in the haematology and cancer patients reflects the existential threat of the disease and may serve as a coping strategy. The high percentage of emotional constructs may mirror the patients' need for further support. The distinct distribution of construct categories in the two different patient samples supports the applicability of the proposed preliminary model.

[Narcissism inventory-90 (NI-90). Empirically-based reduction and identification of items sensitive for change--a questionnaire particularly suited for measuring self-regulatory parameters]. / Narzissmusinventar-90 (NI-90). Empiriegeleitete Itemreduktion und Identifikation veränderungssensitiver Items des Narzissmusinventars zur Messung selbstregulativer Parameter.

By analysing Narcissism Inventories [1] gathered by the admission from 639 consecutive in-patients, as well as a related sample of inventories gathered from 397 consecutive patients (7/93-7/96) by admission and discharge, we examined the possibility of reducing the number of items of the Narcissism Inventory without losing significant information. This examination shows that reducing the inventory to a total of 5 items per scale is reasonable, without a relevant loss of metric quality in the item-reduced scales. In addition, items particularly sensitive to change could be identified and pointedly kept in the new, reduced scales. Through the deliberate selection of these items, it was possible to produce an empirically-guided short-version of the Narcissism Inventory, suited particularly for the examination of clinical process and regulatory parameters. With persistence of the original 18 scales proposed by the authors of the original test, a reduction to a total of 90 items results. The name "Narcissism Inventory-90 (NI-90)" is, therefore, suggested for this new version.

Encoding of movement time by populations of cerebellar Purkinje cells.

One of the earliest computational principles attributed to the cerebellum was the measurement of time. This idea was originally suggested on anatomical grounds, and was taken up again to explain some of the deficits in cerebellar patients. The contribution of the cerebellum to eye movements, in contrast, has traditionally been discussed in the context of motor learning. This view has received support from the loss of saccade adaptation, one of the key examples of motor learning, following lesions of the posterior cerebellar vermis. However, the relationship between the properties of saccade-related vermal Purkinje cells and the behavioural deficits that follow lesions is unclear. Here we report results from single-unit recording experiments on monkeys that reconcile the seemingly unrelated concepts of timing and motor learning. We report that, unlike individual Purkinje cells, the population response of larger groups of Purkinje cells gives a precise temporal signature of saccade onset and offset. Thus a vermal population response may help to determine saccade duration. Modifying the time course of the population response by changing the weights of the contributing individual Purkinje cells, discharging at different times relative to the saccade, would directly translate into changes in saccade amplitude.

Contextual influence on orientation discrimination of humans and responses of neurons in V1 of alert monkeys.

We studied the effects of various patterns as contextual stimuli on human orientation discrimination, and on responses of neurons in V1 of alert monkeys. When a target line is presented along with various contextual stimuli (masks), human orientation discrimination is impaired. For most V1 neurons, responses elicited by a line in the receptive field (RF) center are suppressed by these contextual patterns. Orientation discrimination thresholds of human observers are elevated slightly when the target line is surrounded by orthogonal lines. For randomly oriented lines, thresholds are elevated further and even more so for lines parallel to the target. Correspondingly, responses of most V1 neurons to a line are suppressed. Although contextual lines inhibit the amplitude of orientation tuning functions of most V1 neurons, they do not systematically alter the tuning width. Elevation of human orientation discrimination thresholds decreases with increasing curvature of masking lines, so does the inhibition of V1 neuronal responses. A mask made of straight lines yields the strongest interference with human orientation discrimination and produces the strongest suppression of neuronal responses. Elevation of human orientation discrimination thresholds is highest when a mask covers only the immediate vicinity of the target line. Increasing the masking area results in less interference. On the contrary, suppression of neuronal responses in V1 increases with increasing mask size. Our data imply that contextual interference observed in human orientation discrimination is in part directly related to contextual inhibition of neuronal activity in V1. However, the finding that interference with orientation discrimination is weaker for larger masks suggests a figure-ground segregation process that is not located in V1.

Saccadic dysmetria and adaptation after lesions of the cerebellar cortex.

We studied the effects of small lesions of the oculomotor vermis of the cerebellar cortex on the ability of monkeys to execute and adapt saccadic eye movements. For saccades in one horizontal direction, the lesions led to an initial gross hypometria and a permanent abolition of the capacity for rapid adaptation. Mean saccade amplitude recovered from the initial hypometria, although variability remained high. A series of hundreds of repetitive saccades in the same direction resulted in gradual decrement of amplitude. Saccades in other directions were less strongly affected by the lesions. We suggest the following. (1) The cerebellar cortex is constantly recalibrating the saccadic system, thus compensating for rapid biomechanical changes such as might be caused by muscle fatigue. (2) A mechanism capable of slow recovery from dysmetria is revealed despite the permanent absence of rapid adaptation.