Anarchic-hand syndrome: ERP reflections of lost control over the right hemisphere.

In patients with the callosal type of anarchic-hand syndrome, the left hand often does not act as intended and counteracts the right hand. Reports are scarce about the underlying neurophysiological mechanisms. We report the case G.H. who developed the syndrome after infarction of the left arteria pericallosa. It has been suggested that the syndrome arises out of lacking inhibition from the dominant left hemisphere on the right hemisphere. Yet, in tests of spatial intelligence G.H. performed much better with his "anarchic" left hand than with his dominant right hand, similar to observations commonly reported in split-brain patients. Left-right manual choice responses and event-related EEG potentials to laterally presented stimuli were measured. Asymmetries were evident in G.H.'s behavior and EEG potentials, different from age-matched healthy participants (n=11). His right-hand responses were fast and unaffected by incompatibility with stimulus location, whereas his left-hand responses were variable and accompanied by a large negative central-midline EEG potential, probably reflecting efforts in initiating the response. G.H.'s visual N1 component peaked earlier and was larger at the right than the left side of the scalp, and the P3 component was distinctly reduced at the right side. Both features occurred independent of side of stimulus presentation and side of responding hand. The effort indicated by the midline negativity and the asymmetrically reduced P3 might directly reflect G.H.'s lack of control on his right hemisphere's processing. The faster visual processing of the right hemisphere suggested by the N1 asymmetry might contribute to "anarchic" processing, making the right hemisphere process stimuli before control impulses exert their effect. These neurophysiological results tend to support the split-brain account which assumes that the syndrome arises by the lack of communication between hemispheres that act according to their respective competences.

Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations.

We report the clinical features of the original Chilean family with Kufor-Rakeb syndrome (KRS) that led to the discovery of the ATP13A2 gene at the PARK9 locus. KRS is a rare juvenile-onset autosomal recessive disease characterized by progressive Parkinsonism, pyramidal signs, and cognitive decline in addition to vertical gaze palsy and facial-faucial-finger minimyoclonus. Neurological and neuropsychological examination during a 10-year period, videotaping, neuroimaging, and measurement of DNA methylation of the ATP13A2 promoter region were performed. The youngest 5 of 17 children of nonconsanguineous parents, carrying compound-heterozygous ATP13A2 mutations, had normal development until ages ∼10 to 12 years, when school performance deteriorated and slowness, rigidity, and frequent falls developed. Examination revealed bradykinesia, subtle postural/action tremor, cogwheel rigidity, spasticity, upward gaze palsy, smooth pursuit with saccadic intrusions, and dementia. Additional signs included facial-faucial-finger minimyoclonus, absent postural reflexes, visual/auditory hallucinations, and insomnia. Levodopa response could not be fully judged in this family. T2* magnetic resonance imaging sequences revealed marked diffuse hypointensity of the caudate (head and body) and lenticular nucleus bilaterally. Disease progression was slow including epilepsy, cachexia, and anarthria. Four affected members died after 28.5 ± 5.5 (mean ± SD) years of disease. Two heterozygous carriers, the mother and eldest sibling, showed jerky perioral muscle contractions and clumsiness of hand movements. There was no significant correlation between DNA methylation of the ATP13A2 promoter region and disease progression. The marked caudate and lenticular nucleus T2*-hypointensity suggests that KRS might belong to the family of neurodegenerative diseases associated with brain iron accumulation.

Visual search disorders in acute and chronic homonymous hemianopia: lesion effects and adaptive strategies.

Patients with homonymous hemianopia due to occipital brain lesions show disorders of visual search. In everyday life this leads to difficulties in reading and spatial orientation. It is a matter of debate whether these disorders are due to the brain lesion or rather reflect compensatory eye movement strategies developing over time. For the first time, eye movements of acute hemianopic patients (n= 9) were recorded during the first days following stroke while they performed an exploratory visual-search task. Compared to age-matched control subjects their search duration was prolonged due to increased fixations and refixations, that is, repeated scanning of previously searched locations. Saccadic amplitudes were smaller in patients. Right hemianopic patients were more impaired than left hemianopic patients. The number of fixations and refixations did not differ significantly between both hemifields in the patients. Follow-up of one patient revealed changes of visual search over 18 months. By using more structured scanpaths with fewer saccades his search duration decreased. Furthermore, he developed a more efficient eye-movement strategy by making larger but less frequent saccades toward his blind side. In summary, visual-search behavior of acute hemianopic patients differs from healthy control subjects and from chronic hemianopic patients. We conclude that abnormal visual search in acute hemianopic patients is related to the brain lesion. We provide some evidence for adaptive eye-movement strategies developed over time. These adaptive strategies make the visual search more efficient and may help to compensate for the persisting visual-field loss.

Visual search disorders beyond pure sensory failure in patients with acute homonymous visual field defects.

Patients with homonymous visual field defects (HVFD) are often crucially disabled during self-guided visual exploration of their natural environment. Abnormal visual search may be related to the sensory deficit, deficient spatial orientation or compensatory eye movements. We tested the hypothesis that visual search in HVFD is purely determined by the visual-sensory deficit by comparing nine patients with HVFD due to occipital stroke in an acute stage to nine healthy subjects with technically simulated "virtual" homonymous visual field defects (vHVFD) and to nine controls with normal visual fields. The simulated gaze-contingent visual field defects in vHVFD subjects were individually matched to the patients' HVFD with respect to their size and side. Eye movements were recorded while subjects searched for targets among distractors and indicated target detection by clicks. All patients, in particular those with lesions involving the inferior occipito-temporal (fusiform) gyrus, but also those with small lesions restricted to the visual cortex, showed longer search durations than vHVFD subjects. This was tightly related to the higher number of fixations and particularly "re-fixations" (repeated scanning of fixated items). Working memory across saccades during the search was intact (no increased "re-clicks"). Scanpath strategies were similar in patients and vHVFD subjects. For both groups amplitude and frequency of saccades did not differ between the hemifields. In HVFD patients with acute occipital brain lesions, visual input failure does not fully account for abnormal visual search. It might either result from disconnections of the primary visual cortex to associated occipital and temporal brain areas or reflect an early stage of compensatory eye movements which differ from chronic HVFD patients.

Long-term eye movement recordings with a scleral search coil-eyelid protection device allows new applications.

The search coil technique is regarded as the gold standard in eye movement recordings. The manufacturers of scleral search coils (SSC) do not recommend using them longer than 30 min. The temporal limitations result from potential cornea damage and from irritations of the lid margins and palpebral conjunctiva which subjects perceive as unpleasant. Here we introduce a new coil-eyelid protection device (CEPD) which allows recording intervals up to 2 h with considerably reduced discomfort. Ophthalmic examinations and saccade recordings were used for comparison with the conventional SSC recording technique. In three experiments subjects were examined using SSCs with a commercially available cornea bandage lens on top of the search coil up to 120 min recording time. Ophthalmic testing revealed no apparent harmful effects on eyes or lid surface. Saccade parameters (main sequence) remained unchanged comparing SSC and CEPD recordings. Subjects rated less discomfort by using the CEPD. For the first time we show that SSC recordings can be extended over about 120 min without hazard to the eye, when using an eyelid protection lens. This advanced method allows new applications like eye movement recordings during sleep (rapid eye movements) or perceptional or motor learning tasks, e.g. saccade adaptation paradigms.

Eye-hand coordination in essential tremor.

Patients with essential tremor (ET) or with cerebellar lesions have in common oculomotor abnormalities, with the exception of saccadic eye movements, which do not seem to be involved in ET. Since grasping is prolonged in ET and might be related to saccadic dysmetria, we tested whether simultaneous hand pointing could unmask it. Twelve ET patients and 14 controls performed saccades with and without simultaneous pointing movements to the same targets, and with and without a gap between the disappearance of the fixation point and the appearance of the target. Eye movements were recorded with the magnetic search-coil method, hand movements with an ultrasound-emitting probe. ET patients did not have saccadic dysmetria, and contrary to normal subjects their saccadic latency did not decrease during combined eye-hand movements compared with saccades performed in isolation. Hand movements had a longer duration in ET patients, with decreased peak acceleration, an increased latency of the peak velocity, and peak deceleration. In conclusion, this first study on eye-hand coordination in ET revealed abnormal kinematic changes in the early phase of pointing movements. These changes might be related to cerebellar disease but they are independent of the intention tremor component and saccade performance.

Parametric modulation of cortical activation during smooth pursuit with and without target blanking. an fMRI study.

Smooth pursuit eye movements (SPEM) are performed to track slowly moving visual targets and are accompanied by saccades whenever foveal representation is lost. In the present study, we correlated the cerebral activation as assessed by functional magnetic resonance imaging with parameters of eye movement performance in order to determine the cortical areas involved in the retinal and extraretinal processing of maintaining smooth pursuit velocity (SPV) and generating saccades in 16 healthy males. The stimulus consisted of a target moving at a constant velocity of 10 degrees/s with and without target blanking. During constant target presentation, SPV was positively correlated with the BOLD signal in the right V5 complex and negatively correlated with the BOLD response in the left dorsolateral prefrontal cortex (DLPFC). In the condition with target blanking, additional negative correlations with SPV were found in the left frontal eye field (FEF), the left parietoinsular vestibular cortex (PIVC) and the left angular gyrus. Saccadic frequency was negatively correlated with activations of the right mesial intraparietal sulcus (IPS) during both conditions and the right premotor area during continuous target presentation. We conclude that V5 is directly related to the maintenance of an optimal smooth pursuit velocity during visual feedback, whereas the FEF, PFC, angular gyrus and PIVC are involved in reconstitution and prediction whenever SPV decreases, especially during maintenance of smooth pursuit in the absence of a visual target. Furthermore, we suggest that parietal areas are related to the suppression of saccades during smooth pursuit.

Cerebellar infarction affects visual search.

Recent studies have discussed the role of the cerebellum in not only motor but also cognitive functions, and in particular, fronto-executive operations. Similar to a previous study on hemineglect patients, we recorded eye movements during a visual search task to investigate patients with isolated infarction of the cerebellum compared with controls. Patients showed longer search durations, associated with mild saccadic dysmetria, longer single fixation durations and a higher number of repeated fixations of items. Systematic search strategies were preserved, but less frequent in patients. In conclusion, though basic mechanisms of visual search including spatial memory were not affected by cerebellar lesions, patients' search behaviour was slower and less efficient, indicating a mild deficit of visual attention and motor planning.

Activation of cerebellar hemispheres in spatial memorization of saccadic eye movements: an fMRI study.

What mechanisms allow us to direct a precise saccade to a remembered target position in space? The cerebellum has been proposed to be involved not only in motor and oculomotor control, but also in perceptual and cognitive functions. We used functional MRI (Echoplanar imaging at 1.5 T) to investigate the role of the cerebellum in the control of externally triggered and internally generated saccadic eye movements of high and low memory impact, in six healthy volunteers. Memory-guided saccades to remembered locations of 3 targets (triple-step saccades) in contrast to either central fixation or to visually guided saccades activated the cerebellar hemispheres predominantly within lobuli VI-crus I. The same areas were activated when an analogous visuospatial working memory task was contrasted to the triple-step saccades. Visually guided saccades activated the posterior vermis and the triple-step saccades, contrasted to the working memory task, activated predominantly the posterior vermis and paravermal regions. Our data confirm the primary involvement of the posterior vermis for visually-triggered saccadic eye movements and present novel evidence for a role of the cerebellar hemispheres in the mnemonic and visuospatial control of memory-guided saccades.

Control of hand movements after striatocapsular stroke: high-resolution temporal analysis of the function of ipsilateral activation.

OBJECTIVE: Hemiparesis due to infarction of the middle cerebral artery has become an increasingly important focus of research on cortical plasticity. Positron emission tomography and functional magnetic resonance imaging studies in such patients found involvement of the hemisphere ipsilateral to the affected hand related to movements of this hand. To understand the function of this ipsilateral activation, the present study investigated movement-related electroencephalogram (EEG) potentials in patients and healthy control subjects to measure timing of ipsi- and contralateral activation relative to movement onset. METHODS: Thirteen patients were investigated in their chronic stage. Their pyramidal tracts were affected by infarctions of the middle cerebral artery at striatocapsular level. EEG potentials were recorded from 26 scalp electrodes while patients were pressing a key with their right or left index finger within a warned choice-response task. RESULTS: Beginning 200 ms before responses of the affected hand, there was normal contralateral preponderance of EEG negativity. Briefly after response onset, however, the other unaffected hemisphere, ipsilateral to the responding hand, became additionally active. This pattern did not occur with responses made by the unaffected hand nor in healthy participants. CONCLUSIONS: The timing of the onset of ipsilateral activity precludes its role in response initiation. Rather, this activity may indicate reflex-like activation of the unaffected motor system to compensate for possible failure of the affected hand.

Effects of stimulus-induced saccades on manual response times in healthy elderly and in patients with right-parietal lesions.

Response delays of hemi-neglect patients to invalidly cued left targets in Posner's visual cueing task have been interpreted as reflecting disorders of covert attention, although shifts of overt attention have so far not been systematically measured in patients performing this task. Therefore, we measured saccades (i.e., fast goal-directed eye movements) induced by cues and targets in this task in ten patients with lesions of the right posterior parietal cortex and in age-matched healthy subjects. Participants were not aware that their saccades were studied. Of greatest interest was whether the presence or absence of saccades would modify the patients' response delay with invalidly cued left targets. In both groups, saccades occurred in many trials, key-press responses were slower in saccade trials than in no-saccade trials, and the delay by invalid cues was larger in saccade trials. The patients' responses were in particular delayed if preceded by saccades to the left. Their delay to invalidly cued left targets almost doubled (144 ms vs 76 ms) when only saccade trials were analyzed compared to when only no-saccade trials were analyzed. Thus, overt shifts (saccades) have a similar but larger effect on manual responses than covert shifts of attention. In particular, overt shifts make a considerable contribution to the patients' pathological delay of responses to invalidly cued left targets.