Rebekka Lencer

Neurophysiology and neuroanatomy of smooth pursuit in humans.

Smooth pursuit eye movements enable us to focus our eyes on moving objects by utilizing well-established mechanisms of visual motion processing, sensorimotor transformation and cognition. Novel smooth pursuit tasks and quantitative measurement techniques can help unravel the different smooth pursuit components and complex neural systems involved in its control. The maintenance of smooth pursuit is driven by a combination of the prediction of target velocity and visual feedback about performance quality, thus a combination of retinal and extraretinal information that has to be integrated in various networks. Different models of smooth pursuit with specific in- and output parameters have been developed for a better understanding of the underlying neurophysiological mechanisms and to make quantitative predictions that can be tested in experiments. Functional brain imaging and neurophysiological studies have defined motion sensitive visual area V5, frontal (FEF) and supplementary (SEF) eye fields as core cortical smooth pursuit regions. In addition, a dense neural network is involved in the adjustment of an optimal smooth pursuit response by integrating also extraretinal information. These networks facilitate interaction of the smooth pursuit system with multiple other visual and non-visual sensorimotor systems on the cortical and subcortical level. Future studies with fMRI advanced techniques (e.g., event-related fMRI) promise to provide an insight into how smooth pursuit eye movements are linked to specific brain activation. Applying this approach to neurological and also mental illness can reveal distinct disturbances within neural networks being present in these disorders and also the impact of medication on this circuitry.

Cortical mechanisms of smooth pursuit eye movements with target blanking. An fMRI study.

Smooth pursuit eye movements are evoked by retinal image motion of visible moving objects and can also be driven by the internal representation of a target due to extraretinal mechanisms (e.g. efference copy). To delineate the corresponding neuronal correlates, functional magnetic resonance imaging at 1.5 T was applied during smooth pursuit at 10 °/s with continuous target presentation and target blanking for 1 s to 16 right‐handed healthy males. Eye movements were assessed during scanning sessions by infra‐red reflection oculography. Smooth pursuit performance was optimal when the target was visible but decreased to a residual velocity of about 30% of the velocity observed during continuous target presentation. Random effects analysis of the imaging data yielded an activation pattern for smooth pursuit in the absence of a visual target (in contrast to continuous target presentation) which included a number of cortical areas in which extraretinal information is available such as the frontal eye field, the superior parietal lobe, the anterior and the posterior intraparietal sulcus and the premotor cortex, and also the supplementary and the presupplementary eye field, the supramarginal gyrus, the dorsolateral prefrontal cortex, cerebellar areas and the basal ganglia. We suggest that cortical mechanisms such as prediction, visuo‐spatial attention and transformation, multimodal visuomotor control and working memory are of special importance for maintaining smooth pursuit eye movements in the absence of a visible target.

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.

Primary focal dystonia: evidence for distinct neuropsychiatric and personality profiles

Background: Primary focal dystonia (PFD) is characterised by motor symptoms. Frequent co-occurrence of abnormal mental conditions has been mentioned for decades but is less well defined. In this study, prevalence rates of psychiatric disorders, personality disorders and traits in a large cohort of patients with PFD were evaluated. Methods: Prevalence rates of clinical psychiatric diagnoses in 86 PFD patients were compared with a population based sample (n = 3943) using a multiple regression approach. Furthermore, participants were evaluated for personality traits with the 5 Factor Personality Inventory. Results: Lifetime prevalence for any psychiatric or personality disorder was 70.9%. More specifically, axis I disorders occurred at a 4.5-fold increased chance. Highest odds ratios were found for social phobia (OR 21.6), agoraphobia (OR 16.7) and panic disorder (OR 11.5). Furthermore, an increased prevalence rate of 32.6% for anxious personality disorders comprising obsessive–compulsive (22.1%) and avoidant personality disorders (16.3%) were found. Except for social phobia, psychiatric disorders manifested prior to the occurrence of dystonia symptoms. In the self-rating of personality traits, PFD patients demonstrated pronounced agreeableness, conscientiousness and reduced openness. Conclusions: Patients with PFD show distinct neuropsychiatric and personality profiles of the anxiety spectrum. PFD should therefore be viewed as a neuropsychiatric disorder rather than a pure movement disorder.

Eye movements and psychiatric disease.

Purpose of reviewDuring the past year a number of studies have been published on eye movement dysfunction in patients with psychiatric disease. According to the mainstream of modern neuropsychiatric research, these studies cover either genetic aspects or the results of pharmacological manipulation. Recent findingsA few studies addressed impaired smooth pursuit eye movements (eye tracking dysfunction) in unaffected relatives of psychiatric patients, and were important in excluding non-specific effects (e.g. medication) and isolating genetic predisposition to the disease. This predisposition could be demonstrated in families of schizophrenic patients irrespective of whether the index case was sporadic or familial. One large study demonstrated pathological distributions of various parameters of smooth pursuit eye movement performance in groups of schizophrenic patients and their relatives. However, another study challenged the specificity of eye tracking dysfunction as a trait marker for schizophrenia by showing that its prevalence was identical among relatives of patients with affective disorder and schizophrenia. Eye tracking dysfunction was associated with two gene polymorphisms that interfere with dopamine metabolism and are thus reasonable candidate genes for the predisposition to schizophrenia. The influence of nicotine and neuroleptic drugs on eye movement performance was studied in schizophrenic patients. Nicotine improved smooth pursuit performance in three studies, one of which attributed this finding to enhanced attention. Two groups of schizophrenic patients treated with two different atypical neuroleptic drugs, risperidone and olanzapine, did not differ in a battery of saccadic tasks. SummaryEye movements provide an important tool to measure pharmacological effects in patients and unravel genetic traits in psychiatric disease.

Reduced neuronal activity in the V5 complex underlies smooth-pursuit deficit in schizophrenia: evidence from an fMRI study

Smooth-pursuit eye movements are the essential tool for a clear and stable visual perception of our environment by matching eye velocity to the velocity of moving objects. However, in about 50% of schizophrenic patients, this ability is disturbed. To reveal the cortical mechanisms that underlie this deficit, eye velocity-related neuronal activity was analyzed by functional magnetic resonance imaging (fMRI). Blocks of constant velocity ramps (10 degrees/s) were presented to 17 patients with schizophrenia and 16 matched controls while assessing smooth-pursuit velocity (SPV) during scanning sessions. Using random-effects analysis, the parametric modulation of brain hemodynamic responses related to SPV was compared between both groups. In schizophrenic patients, reduced SPV was significantly correlated with a focal decrease of the hemodynamic response in the V5 complex (t = 4.21, P(FWE-corrected) = 0.005). Our results provide direct evidence for reduced neuronal activity in V5 as one major factor underlying abnormal SPV in schizophrenia and suggest impaired motion perception. They confirm hypotheses about a V5 deficit derived from psychophysiological studies with schizophrenic patients in which deficient motion perception (especially velocity discrimination) was associated with impaired smooth-pursuit performance.

Cortical mechanisms of retinal and extraretinal smooth pursuit eye movements to different target velocities

Smooth pursuit eye movements (SPEM) are used to maintain focus upon moving targets. The generation of SPEM velocity is controlled by retinal information and extraretinal signals. Although there is a wealth of studies investigating retinal and extraretinal SPEM control, the main questions regarding the cortical mechanisms involved in the processing of SPEM to different stimulus velocities are still unresolved. We applied an innovative event-related fMRI-design by presenting target ramps at different velocities (5, 10, 15, 20 degrees/s) with both continuous target presentation and intervals of target blanking. The stimulus parameters were integrated into the statistical model and eye movements were registered to confirm SPEM performance. Our results clearly demonstrate that in humans the oculomotor network (V5, frontal and supplementary eye fields, lateral intraparietal area) is engaged in the processing of retinal and extraretinal SPEM velocity. Within this network neural activity increases with increasing target velocity. During extraretinal SPEM, additional engagement of the dorsolateral prefrontal cortex, angular gyrus, parahippocampal gyrus and superior temporal gyrus occurs. These regions encode cognitive functions such as memory, attention and monitoring. The activation of the inferior parietal cortex seems to be related to the interaction between velocity and blanking thereby underlining its relevance for task switching and sensorimotor transformation.

Different extraretinal neuronal mechanisms of smooth pursuit eye movements in schizophrenia: An fMRI study.

Smooth pursuit eye movements (SPEM) are necessary to follow slowly moving targets while maintaining foveal fixation. In about 50% of schizophrenic patients SPEM velocity is reduced. In this study we were interested in identifying the cortical mechanisms associated with extraretinal processing of SPEM in schizophrenic patients. During condition A, patients and healthy subjects had to pursue a constantly visible target (10 degrees /s). During condition B the target was blanked out for 1000 ms while subjects were instructed to continue SPEM. Eye movement data were assessed during scanning sessions by a limbus tracker. During condition A, reduced SPEM velocity in patients was associated with reduced activation of the right ventral premotor cortex and increased activation of the left dorsolateral prefrontal cortex, the right thalamus and the Crus II of the left cerebellar hemisphere. During condition B, SPEM velocity was reduced to a similar extent in both groups. While in patients a decrease in activation was observed in the right cerebellar area VIIIA, the activation of the right anterior cingulate, the right superior temporal cortex, and the bilateral frontal eye fields was increased. The results implicate that schizophrenic patients employ different strategies during SPEM both with and without target blanking than healthy subjects. These strategies predominantly involve extraretinal mechanisms.

Limbic and Frontal Cortical Degeneration Is Associated with Psychiatric Symptoms in PINK1 Mutation Carriers

BACKGROUND Mutations in the PINK1 gene can cause Parkinsons disease and are frequently associated with psychiatric symptoms that might even precede motor signs. METHODS To determine whether specific gray matter degeneration of limbic and frontal structures might be liable to different psychiatric symptoms in PINK1 mutation carriers, observer-independent voxel-based morphometry was applied to high-resolution magnetic resonance images of 14 PINK1 mutation carriers from a large German family and 14 age- and gender-matched healthy control subjects. RESULTS Psychiatric diagnoses in PINK1 mutation carriers comprised major depression without psychotic symptoms and schizophrenia-spectrum, panic, adjustment, and obsessive-compulsive personality disorders. As hypothesized, the categorical comparison between all PINK1 mutation carriers and control subjects demonstrated atrophy of limbic structures, especially the hippocampus and parahippocampus. More specifically, multiple regression analysis considering all psychiatric subscores simultaneously displayed different frontal (prefrontal, dorsolateral, and premotor cortex) and limbic (parahippocampus and cingulate) degeneration patterns. The duration of the psychiatric disease was also correlated with the extent of limbic and frontal gray matter volume decrease. CONCLUSIONS Our results support the hypothesis that limbic and frontal gray matter alterations could explain various psychiatric symptoms observed in PINK1 mutation carriers. Factors determining individual susceptibility to degeneration of certain brain areas remain to be elucidated in future studies.

Evidence from increased anticipation of predictive saccades for a dysfunction of fronto-striatal circuits in obsessive-compulsive disorder.

In obsessive-compulsive disorder (OCD), a dysfunction of neuronal circuits involving prefrontal areas and the basal ganglia is discussed that implies specific oculomotor deficits. Performance during reflexive and predictive saccades, antisaccades and predictive smooth pursuit was compared between patients with OCD (n=22), patients with schizophrenia (n=21) and healthy subjects (n=24). Eye movements were recorded by infrared reflection oculography. In both patient groups, higher frequencies of anticipatory saccades with reduced amplitudes in the predictive saccade task were observed. Additionally, reduced smooth pursuit eye velocity and increased frequencies of saccadic intrusions during smooth pursuit as well as increased error rates in the antisaccade task were demonstrated for patients suffering from schizophrenia. Patients with OCD and schizophrenia revealed different patterns of oculomotor impairment: whereas increased anticipation of predictive saccades provides evidence for a dysfunction of the circuit between the frontal eye field and the basal ganglia in both groups, results from the antisaccade task imply additional deficits involving the dorsolateral prefrontal cortex in schizophrenic patients. Furthermore, the cortical network for smooth pursuit (especially the frontal eye field) is also assumed to be disturbed in schizophrenia.