Disconnection in a left-hemispheric temporo-parietal network impairs multiplication fact retrieval.

Arithmetic fact retrieval has been suggested to recruit a left-lateralized network comprising perisylvian language areas, parietal areas such as the angular gyrus (AG), and non-neocortical structures such as the hippocampus. However, the underlying white matter connectivity of these areas has not been evaluated systematically so far. Using simple multiplication problems, we evaluated how disconnections in parietal brain areas affected arithmetic fact retrieval following stroke. We derived disconnectivity measures by jointly considering data from n = 73 patients with acute unilateral lesions in either hemisphere and a white-matter tractography atlas (HCP-842) using the Lesion Quantification Toolbox (LQT). Whole-brain voxel-based analysis indicated a left-hemispheric cluster of white matter fibers connecting the AG and superior temporal areas to be associated with a fact retrieval deficit. Subsequent analyses of direct gray-to-gray matter disconnections revealed that disconnections of additional left-hemispheric areas (e.g., between the superior temporal gyrus and parietal areas) were significantly associated with the observed fact retrieval deficit. Results imply that disconnections of parietal areas (i.e., the AG) with language-related areas (i.e., superior and middle temporal gyri) seem specifically detrimental to arithmetic fact retrieval. This suggests that arithmetic fact retrieval recruits a widespread left-hemispheric network and emphasizes the relevance of white matter connectivity for number processing.

Training of vertical versus horizontal reading in patients with hemianopia - a randomized and controlled study.

HYPOTHESIS: Patients with hemianopic field defects (HFD) might benefit from reading text in vertical orientation if they place the text in the seeing hemifield along the vertical midline. METHODS: We assigned 21 patients with HFD randomly to either vertical or horizontal reading training. They trained reading single lines of texts from a computer screen at home for 2 × 30 min/day, 5 days/week, for 4 weeks. The main outcome variable was reading speed (RS) during reading standardized paragraphs of printed text (IReST) aloud. RS was assessed before training (T1), directly after training (T2) and 4 weeks later (T3). Quality of life (QoL) was assessed by Impact of Visual Impairment (IVI) questionnaire. RESULTS: Vertical training improved RS in the vertical direction significantly. Only patients with right HFD benefited. Horizontal training improved RS in horizontal diection significantly, but much more in patients with left than in those with right HFD. Both effects remained stable at T3. RS during training at the computer improved highly significantly and correlated strongly with RS of printed text (Pearson r= > 0.9). QoL: Vertical training showed a statistically significant improvement in the complete IVI-score, patients with right HFD in the emotional IVI-score. CONCLUSIONS: The improvements of RS were specific for the training. The stable effect indicates that the patients can apply the newly learned strategies to everyday life. The side of the HFD plays an essential role: Left-HFD patients benefitted from horizontal training, right-HFD patients from vertical training. However, the vertical RS did not reach the level of horizontal RS. The study was registered in the German Clinical Trials register (DRKS-ID: DRKS00018843).

Assessing body image in anorexia nervosa using biometric self-avatars in virtual reality: Attitudinal components rather than visual body size estimation are distorted.

BACKGROUND: Body image disturbance (BID) is a core symptom of anorexia nervosa (AN), but as yet distinctive features of BID are unknown. The present study aimed at disentangling perceptual and attitudinal components of BID in AN. METHODS: We investigated n = 24 women with AN and n = 24 controls. Based on a three-dimensional (3D) body scan, we created realistic virtual 3D bodies (avatars) for each participant that were varied through a range of ±20% of the participants' weights. Avatars were presented in a virtual reality mirror scenario. Using different psychophysical tasks, participants identified and adjusted their actual and their desired body weight. To test for general perceptual biases in estimating body weight, a second experiment investigated perception of weight and shape matched avatars with another identity. RESULTS: Women with AN and controls underestimated their weight, with a trend that women with AN underestimated more. The average desired body of controls had normal weight while the average desired weight of women with AN corresponded to extreme AN (DSM-5). Correlation analyses revealed that desired body weight, but not accuracy of weight estimation, was associated with eating disorder symptoms. In the second experiment, both groups estimated accurately while the most attractive body was similar to Experiment 1. CONCLUSIONS: Our results contradict the widespread assumption that patients with AN overestimate their body weight due to visual distortions. Rather, they illustrate that BID might be driven by distorted attitudes with regard to the desired body. Clinical interventions should aim at helping patients with AN to change their desired weight.

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 line bisection bias as a deficit of proportional reasoning - evidence from number line estimation in neglect.

This study aimed to investigate whether neurological patients presenting with a bias in line bisection show specific problems in bisecting a line into two equal parts or their line bisection bias rather reflects a special case of a deficit in proportional reasoning more generally. In the latter case, the bias should also be observed for segmentations into thirds or quarters. To address this question, six neglect patients with a line bisection bias were administered additional tasks involving horizontal lines (e.g., segmentation into thirds and quarters, number line estimation, etc.). Their performance was compared to five neglect patients without a line bisection bias, 10 patients with right hemispheric lesions without neglect, and 32 healthy controls. Most interestingly, results indicated that neglect patients with a line bisection bias also overestimated segments on the left of the line (e.g., one third, one quarter) when dissecting lines into parts smaller than halves. In contrast, such segmentation biases were more nuanced when the required line segmentation was framed as a number line estimation task with either fractions or whole numbers. Taken together, this suggests a generalization of line bisection bias towards a segmentation or proportional processing bias, which is congruent with attentional weighting accounts of line bisection/neglect. As such, patients with a line bisection bias do not seem to have specific problems bisecting a line, but seem to suffer from a more general deficit processing proportions.

Vertical and horizontal reading training in patients with hemianopia and its effect on reading eye movements.

Vertical reading training (VRTr) increases reading speed (RS) significantly in patients with hemianopic field defects (HFD). We ask, how eye movements (EM) contribute to this improvement and whether EM-behavior is affected by the side of HFD. Twenty-one patients, randomly assigned to VRTr or horizontal RTr, trained reading single lines from a screen at home, for 4 weeks. In the clinic, we recorded EM while reading short sentences aloud from a screen before training (T1), directly (T2) and 4 weeks afterwards (T3). RS-screen was correlated with RS during reading printed paragraphs (RS-print) to assess the transfer to everyday life. RS-screen and RS-print correlated positively (horizontal: r > 0.8, vertical: r > 0.9) at all times. Vertical RS did not exceed horizontal RS. We found significant negative correlations of EM-variables and RS-print: in right-HFD with the number of forward saccades (T1: r = - 0.79, T2: r = - 0.94), in left-HFD with the steps during return sweeps (T1: r = - 0.83, T2: r = - 0.56). Training effects remained stable at T3. EM-improvement was specific for the RTr and the side of the HFD: in right-HFD fewer forward saccades after VRTr, in left-HFD fewer steps during return sweeps after HRTr. RTr on a screen transfers to reading printed text in real-life situations.Trial registration: The study was retrospectively registered in the German Clinical Trials register: DRKS-ID: DRKS00018843, March 13th, 2020.

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.

Abnormally speeded saccades to ipsilesional targets in patients with spatial neglect.

We mapped the distribution of saccadic reaction times (SRTs) in the visual field of patients with spatial neglect in order to characterise the topography of the bias in spatial orientation peculiar to this disorder. LED-generated stimuli were lit randomly in one of four positions (+/-5 degrees , +/-10 degrees , +/-20 degrees , +/-30 degrees ) along the horizontal meridian in blocks of either ipsilesional or contralesional presentations. Patients were asked to move the gaze as quickly as possible from central fixation to target upon its appearance. Unlike control subjects, patients with neglect showed an asymmetric distribution of visuo-motor performance in the two hemifields with an increasing impairment in target detection and saccadic reaction at increasing eccentricities in the contralesional field. In contrast, in the ipsilesional field they showed abnormally speeded SRTs at 5 degrees and 10 degrees , outperforming even healthy subjects. Latency of saccades increased again at more peripheral ipsilesional locations (20 degrees and 30 degrees ) where there was also a tendency for a higher omission rate as compared to control groups. These results indicate that in neglect patients the spatial orientation bias, as witnessed by saccadic performance, specifically affects an off-centred sector of the ipsilesional space, and this is in keeping with evidence from a previous study using a manual RT paradigm. The generality of this phenomenon across different types of motor response suggests that it depends upon abnormal mechanisms of spatial coding interfering with perceptual processing and orienting behaviour.

A general deficit of the 'automatic pilot' with posterior parietal cortex lesions?

Lesions of the parieto-occipital junction (POJ) in humans cause gross deviations of reaching movements and impaired grip formation if the targets are located in the subjects' peripheral visual field. Movements to central targets are typically less impaired. This disorder has been termed "optic ataxia". It has been suggested that a general deficit of online corrections under central as well as peripheral viewing conditions might be sufficient to explain this discrepancy. According to this hypothesis, patients with optic ataxia should demonstrate an impaired online correction of grip aperture under central viewing conditions if the target object changes its size during the grasping movement. We investigated this prediction in a patient with optic ataxia (I.G.) in a virtual visuo-haptic grasping task. We imposed an isolated need for online corrections of the hand aperture independently of positional changes of the target object. While we found some general inaccuracies of her grasping movements, the patient did not show a specific impairment of online adjustment of grip aperture. On the contrary, I.G. smoothly adjusted her grip aperture comparable to healthy subjects. A general deficit of fast movement correction affecting targets in peripheral as well as central visual fields thus does not appear to account for the overt visuomotor deficits in optic ataxia. Rather, it seems more likely that an anatomical dissociation between visuomotor pathways related to actions in the central and in the peripheral visual field underlies the dissociation of visuomotor performance depending on the retinotopic target position in optic ataxia.

Deviation of eyes and head in acute cerebral stroke.

BACKGROUND: It is a well-known phenomenon that some patients with acute left or right hemisphere stroke show a deviation of the eyes (Prévost's sign) and head to one side. Here we investigated whether both right- and left-sided brain lesions may cause this deviation. Moreover, we studied the relationship between this phenomenon and spatial neglect. In contrast to previous studies, we determined not only the discrete presence or absence of eye deviation with the naked eye through clinical inspection, but actually measured the extent of horizontal eye-in-head and head-on-trunk deviation. In further contrast, measurements were performed early after stroke onset (1.5 days on average). METHODS: Eye-in-head and head-on-trunk positions were measured at the bedside in 33 patients with acute unilateral left or right cerebral stroke consecutively admitted to our stroke unit. RESULTS: Each single patient with spatial neglect and right hemisphere lesion showed a marked deviation of the eyes and the head to the ipsilesional, right side. The average spontaneous gaze position in this group was 46 degrees right, while it was close to the saggital body midline (0 degrees ) in the groups with acute left- or right-sided stroke but no spatial neglect as well as in healthy subjects. CONCLUSION: A marked horizontal eye and head deviation observed approximately 1.5 days post-stroke is not a symptom associated with acute cerebral lesions per se, nor is a general symptom of right hemisphere lesions, but rather is specific for stroke patients with spatial neglect. The evaluation of the patient's horizontal eye and head position thus could serve as a brief and easy way helping to diagnose spatial neglect, in addition to the traditional paper-and-pencil tests.

Impaired implicit learning and feedback processing after stroke.

The ability to learn is assumed to support successful recovery and rehabilitation therapy after stroke. Hence, learning impairments may reduce the recovery potential. Here, the hypothesis is tested that stroke survivors have deficits in feedback-driven implicit learning. Stroke survivors (n=30) and healthy age-matched control subjects (n=21) learned a probabilistic classification task with brain activation measured using functional magnetic resonance imaging in a subset of these individuals (17 stroke and 10 controls). Stroke subjects learned slower than controls to classify cues. After being rewarded with a smiley face, they were less likely to give the same response when the cue was repeated. Stroke subjects showed reduced brain activation in putamen, pallidum, thalamus, frontal and prefrontal cortices and cerebellum when compared with controls. Lesion analysis identified those stroke survivors as learning-impaired who had lesions in frontal areas, putamen, thalamus, caudate and insula. Lesion laterality had no effect on learning efficacy or brain activation. These findings suggest that stroke survivors have deficits in reinforcement learning that may be related to dysfunctional processing of feedback-based decision-making, reward signals and working memory.

Exploratory saccades show no direction-specific deficit in neglect.

In patients with spatial neglect, contralesional reflexive saccades toward suddenly appearing targets show direction-specific deficits. We examined whether these deficits also occur during free exploration of space. Neglect patients' voluntary eye movements showed reduced amplitudes for saccades in all directions but no direction-specific deficit. The results argue against an interpretation of spatial neglect as a general deficit to disengage attention or to program saccades in contralesional direction.

The origin of contraversive pushing: evidence for a second graviceptive system in humans.

BACKGROUND: Stroke patients may exhibit the peculiar behavior of actively pushing away from the nonhemiparetic side, leading to lateral postural imbalance and a tendency to fall toward the paralyzed side. This phenomenon has been called the "pusher syndrome." OBJECTIVE: The current study analyzes the mechanism leading to contraversive pushing. METHODS: The subjective postural vertical (SPV) and subjective visual vertical (SVV) were determined in five consecutively admitted patients with severe contraversive pushing and in controls. Whereas adjustment of the SPV reflects the perceived upright orientation of the body, the SVV provides a sensitive and direction-specific measurement of peripheral and central vestibular dysfunction. RESULTS: The deficit leading to contraversive pushing is an altered perception of the body's orientation in relation to gravity. Pusher patients experience their body as oriented "upright" when it is tilted 18 degrees to the nonhemiparetic, ipsilesional side. In contrast, perception of the SVV was undisturbed. CONCLUSIONS: A separate pathway seems to be present in humans for sensing the orientation of gravity apart from the one for orientation perception of the visual world. This second graviceptive system decisively contributes to humans' control of upright body posture. Contraversive pushing occurring after stroke lesions may represent the behavioral correlate of a disturbed neural representation of this system.

Deficits of attention in acute and recovered visual hemi-neglect.

Three patients with right-sided lesions and, in two cases, clinically manifest neglect had to compare and to name stimuli presented tachistoscopically either bilateral-simultaneously or unilaterally in the LVF and/or RVF. Whereas there was no difference between unilateral LVF and RVF presentation, "extinction" of the LVF on bilateral stimulation occurred in both the acute and recovered stages. This deficit could be compensated by reducing information analysis in the RVF, thereby provoking covert shifting of attention to the LVF. The results suggest a common mechanism underlying visual neglect and "extinction" with three components--two affecting the directionally specific covert orienting and shifting of attention and one affecting the directionally non-specific processing of information by sequential analysis. The course of recovery is determined by improvement in the directionally specific shifting of attention.

Ocular space exploration in the dark and its relation to subjective and objective body orientation in neglect patients with parietal lesions.

Eye movements of neglect patients with right parietal lesions were recorded during ocular searching for a (non-existent) target in complete darkness. With respect to the objective orientation of the sagittal midplane, ocular exploration was biased toward the ipsilesional side. However, in relation to the patients' subjective localization of the sagittal midplane in space, exploratory eye movements were symmetrically distributed to the subjective "left" and "right" as observed in non-brain-damaged controls. The present results further support the hypothesis that the essential aspect leading to spatial neglect is a disturbance of those cortical structures that are crucial for computing egocentric, body-centred coordinates that allow use to determine our body position in space and that are necessary for visuomotor coordination and exploration of space. In neglect patients the central coordinate transformation seems to work with a systematic error resulting in a deviation of the spatial reference frame to the ipsilesional side. Consequences of this deviation are a displacement of subjective localization of body orientation and--to the same degree--of the spatial area in which motor behavior (here exploratory eye movements) is executed.

Abnormal eye movement behaviour during text reading in neglect syndrome: a case study.

The eye movement behaviour of a patient suffering from a right basal ganglia infarction with a left-sided hemineglect but without any visual field defects was investigated during reading. The eye movements were registered by means of an i.r. light technique (pupil-corneal reflection method). The main findings were abnormal return sweeps. Whereas in normal readers the end of one line of text is linked to the beginning of the new line by a long leftward saccade, the return sweeps of the hemineglect patient stereotypically ended in the middle of the next line. They were followed by sequences of short saccades indicating silent backward reading until a linguistically plausible continuation of sentences from the previous line was found, irrespective of the actual beginning of text. The shortened return sweeps could not be attributed to a general oculomotor disturbance. The spatial border for the occurrence of the patient's abnormal scanning pattern (left half of texts) clearly did not depend on a retinal coordinate frame of reference but rather has to be attributed to a different body-centred reference system.

Inflexibility of mental planning: a characteristic disorder with prefrontal lobe lesions?

Inflexibility of mental planning processes has repeatedly been discussed to represent a specific disorder resulting from human frontal lobe lesions. Patient groups suffering from acute or chronic unilateral frontal (medial, lateral) or retrorolandic (temporal, parietal) lesions and nonbrain-damaged controls were requested to mirror and to reverse mentally a maze structure that had been learned by the covered maze presentation technique (KARNATH et al., Neuropsychologia 29, 271-290, 1991). The patients with acute frontal lesions were impaired to adapt the acquired mental plan to the new (but related) problem and made more errors than those with acute temporal or parietal lesions and controls. However, no impaired plan modification was detected in patients with chronic frontal brain lesions. The difference of task performance in the acute and chronic (recovered) stage of frontal brain damage is discussed.

Is space representation distorted in neglect?

It has been argued that neglect of contralateral stimuli following brain damage might be associated with either a compressed or an anisometric neural representation of space along the earth-horizontal axis. Two different models have been put forward. One model proposes a uniform compression of subjective space, while the other envisages an expansion on one side of space and a compression on the other. We tested these models by determining neglect patients' perception of spatial distances in the horizontal plane. The models differ concerning the expected degree of under- vs overestimation of distances in the left and right hemispace. In the first experiment, patients were asked to position ten red LEDs equidistantly along a semicircle, which was located horizontally in front of them at eye level. A second experiment compared the patients' subjective perception of short, medium and long distances extending into left and right hemispace. We found no evidence for any compression or expansion, nor for anisometry along the earth-horizontal axis. These findings argue against a distortion of subjective space along the horizontal axis in patients with neglect which could account for their failure to orient towards and to explore the contralesional parts of space.

Mental planning and anticipatory processes with acute and chronic frontal lobe lesions: a comparison of maze performance in routine and non-routine situations.

A series of computerized mazes were masked during presentation allowing only partial view of their structure. Patients suffering from acute or chronic unilateral frontal (medial, lateral) or retrorolandic (temporal, parietal) lesions and non-brain-damaged controls were required to pass through the mazes repeatedly, until they solved them without reaching a dead end. Because the mazes could not be viewed in their entirety at any one time, the subjects were forced to mentally generate and apply a plan of the maze. The first ("non-routine" situation), the second and the last ("routine" situation) trials of the mazes were analysed separately. The prefrontal cortex is supposed to subserve important functions in the planning of behaviour in unfamiliar, non-routine situations. Shallice (Phil. Trans. R. Soc. Lond. B298, 199-209, 1982; From Neuropsychology to Mental Structure, Cambridge University Press, Cambridge, 1988) therefore postulated that the behaviour of patients with frontal lobe lesions should not be disturbed in routine situations, but rather these patients should exhibit difficulties in dealing with new and unfamiliar situations. In the present investigation, patients with acute and chronic frontomedial lesions exhibited deficits in generating mental plans. Patients with acute frontomedial lesions made a larger number of errors in their second trials and subsequently required more trials to reach task criterium. Patients with chronic frontomedial lesions showed more frequent rule-breaking behaviour in their second trials. The analysis of maze performance in the first trial and that trial in which task criterion was achieved, showed that frontal lobe patients were impaired in neither routine nor non-routine situations. The observed results suggest a modification concerning Shallice's assumptions. Patients with frontomedial lesions are not generally incapable of dealing with non-routine situations. But they seem to be slower than patients with retrorolandic lesions and controls in profiting from experiences made in an unfamiliar, non-routine situation represented by the first explorations of new maze problems. This deficit can possibly be explained by the observation that anticipatory processes or the formation of expectations about possibly correct decisions in non-routine situations were altered in acute and chronic frontomedial patients. When these patients reached a maze intersection for the first time and therefore had no information about the continuation of the correct path, they showed significantly different intuitive directional decisions when compared to controls.

Kinematics of goal-directed arm movements in neglect: control of hand in space.

The present study investigated unrestrained, three-dimensional arm movements during goal-directed pointing in five patients with clinically manifest neglect to targets positioned either in the center or the left and right hemispace. Five patients with unilateral right hemispheric lesions without neglect and six healthy subjects served as controls. All subjects were able to point to these targets. Terminal accuracy of pointing did not differ between the three groups along the horizontal, vertical and anterior-posterior axis. Subjects' hand trajectories did not reveal direction-specific deviations from a straightline hand path. Our data show that deviations in the trajectories toward the ipsilesional side are not characteristic for patients with spatial neglect. We argue that exploratory and goal-directed motor behavior might not share the same egocentric, body-centered reference frame. A spatial reference frame for exploratory behavior is disturbed in patients with neglect resulting in a failure to explore the contralesional part of space by eye or limb movements. Its failure does not induce a spatial bias in hand trajectory formation during goal-directed arm movements in peripersonal space. Such deviations of reaching or pointing rather seem to be characteristic for patients with optic ataxia.