Prominent Eye Movements Research Articles

Septin-5 and -7-IgGs: Neurologic, Serologic, and Pathophysiologic Characteristics.

We sought to determine clinical significance of neuronal septin autoimmunity and evaluate for potential IgG effects. Septin-IgGs were detected by indirect immunofluorescence assays (IFAs; mouse tissue and cell based) or Western blot. IgG binding to (and internalization of) extracellular septin epitopes were evaluated for by live rat hippocampal neuron assay. The impact of purified patient IgGs on murine cortical neuron function was determined by recording extracellular field potentials in a multielectrode array platform. Septin-IgGs were identified in 23 patients. All 8 patients with septin-5-IgG detected had cerebellar ataxia, and 7 had prominent eye movement disorders. One of 2 patients with co-existing septin-7-IgG had additional psychiatric phenotype (apathy, emotional blunting, and poor insight). Fifteen patients had septin-7 autoimmunity, without septin-5-IgG detected. Disorders included encephalopathy (11; 2 patients with accompanying myelopathy, and 2 were relapsing), myelopathy (3), and episodic ataxia (1). Psychiatric symptoms (≥1 of agitation, apathy, catatonia, disorganized thinking, and paranoia) were prominent in 6 of 11 patients with encephalopathic symptoms. Eight of 10 patients with data available (from 23 total) improved after immunotherapy, and a further 2 patients improved spontaneously. Staining of plasma membranes of live hippocampal neurons produced by patient IgGs (subclasses 1 and 2) colocalized with pre- and post-synaptic markers. Decreased spiking and bursting behavior in mixed cultures of murine glutamatergic and GABAergic cortical neurons produced by patient IgGs were attributable to neither antigenic crosslinking and internalization nor complement activation. Septin-IgGs are predictive of distinct treatment-responsive autoimmune central nervous system (CNS) disorders. Live neuron binding and induced electrophysiologic effects by patient IgGs may support septin-specific pathophysiology. ANN NEUROL 2022;92:1090-1101.

Elements of exogenous attentional cueing preserved during optokinetic motion of the visual scene.

Navigating through our environment raises challenges for perception by generating salient background visual motion and eliciting prominent eye movements to stabilise the retinal image. It remains unclear if exogenous spatial attentional orienting is possible during background motion and the eye movements it causes and whether this compromises the underlying neural processing. To test this, we combined exogenous orienting, visual scene motion, and electroencephalography (EEG). A total of 26 participants viewed a background of moving black and grey bars (optokinetic stimulation). We tested for effects of non-spatially predictive peripheral cueing on visual motion discrimination of a target dot, presented either at the same (valid) or opposite (invalid) location as the preceding cue. Valid cueing decreased reaction times not only when participants kept their gaze fixed on a central point (fixation blocks) but also even when there was no fixation point, so that participants performed intensive, repetitive tracking eye movements (eye movement blocks). Overall, manual response reaction times were slower during eye movements. Cueing also produced reliable effects on neural activity on either block, including within the first 120 ms of neural processing of the target. The key pattern with larger event-related potential (ERP) amplitudes on invalid versus valid trials showed that the neural substrate of exogenous cueing was highly similar during eye movements or fixation. Exogenous peripheral cueing and its neural correlates are robust against distraction from the moving visual scene, important for perceptual cognition during navigation.

Central nystagmus in progressive supranuclear palsy: A neglected clinical feature?

BackgroundProgressive supranuclear palsy (PSP) features parkinsonism characterized by early postural instability, falls and prominent eye movement abnormalities that consist of saccadic slowing, followed by gaze limitation. Nystagmus is not considered typical for PSP, being more commonly associated with multiple system atrophy. ObjectivesTo describe the prevalence and phenomenology of nystagmus in patients with PSP. Methods42 patients with probable PSP underwent detailed clinical eye movement examination. Patients with nystagmus performed video-nystagmography. T-test, Chi-Square test and Wilcoxon signed-rank test were used to test differences in demographic data, disease duration and PSP subtype between patients with and without nystagmus, and for analysis of video-nystagmographic data. ResultsAmong 42 patients with PSP, we identified 15 patients (35,7%) with gaze-evoked nystagmus, predominantly horizontal. Clinically, 10/15 patients had symmetrical or asymmetrical gaze - evoked nystagmus (Type 1), while 5/15 patients had dissociated gaze-evoked nystagmus related to internuclear ophthalmoplegia (Type 2). Nystagmus and eye movement abnormalities were further characterized by video-nystagmography. There was no significant difference in age, disease duration or PSP subtypes between patients with and without nystagmus. ConclusionCentral nystagmus is present in more than a third of patients with progressive supranuclear palsy. It may present as symmetrical or asymmetrical gaze-evoked nystagmus or as dissociated gaze-evoked nystagmus related to internuclear ophthalmoplegia and probably arises from neurodegeneration of the neural integrator. Nystagmus in PSP has been a hitherto under-described feature and its presence should not deter clinicians from a diagnosis of PSP.

Following Forrest Gump: Smooth pursuit related brain activation during free movie viewing

Most fMRI studies investigating smooth pursuit (SP) related brain activity have used simple synthetic stimuli such as a sinusoidally moving dot. However, real-life situations are much more complex and SP does not occur in isolation but within sequences of saccades and fixations. This raises the question whether the same brain networks for SP that have been identified under laboratory conditions are activated when following moving objects in a movie.Here, we used the publicly available studyforrest data set that provides eye movement recordings along with 3 ​T fMRI recordings from 15 subjects while watching the Hollywood movie “Forrest Gump”. All three major eye movement events, namely fixations, saccades, and smooth pursuit, were detected with a state-of-the-art algorithm. In our analysis, smooth pursuit (SP) was the eye movement of interest, while saccades were acting as the steady state of viewing behaviour due to their lower variability. For the fMRI analysis we used an event-related design modelling saccades and SP as regressors initially. Because of the interdependency of SP and content motion, we then added a new low-level content motion regressor to separate brain activations from these two sources.We identified higher BOLD-responses during SP than saccades bilaterally in MT+/V5, in middle cingulate extending to precuneus, and in the right temporoparietal junction. When the motion regressor was added, SP showed higher BOLD-response relative to saccades bilaterally in the cortex lining the superior temporal sulcus, precuneus, and supplementary eye field, presumably due to a confounding effect of background motion. Only parts of V2 showed higher activation during saccades in comparison to SP.Taken together, our approach should be regarded as proof of principle for deciphering brain activity related to SP, which is one of the most prominent eye movements besides saccades, in complex dynamic naturalistic situations.

Autoimmune septin-5 cerebellar ataxia.

ObjectiveTo report a form of autoimmune cerebellar ataxia in which antibodies target septin-5, a guanosine triphosphate (GTP)-binding neural protein involved in neurotransmitter exocytosis.MethodsArchived sera and CSF specimens with unclassified synaptic antibodies were re-evaluated by tissue-based indirect immunofluorescence assay. Autoantigens were identified by Western blot and mass spectrometry. Recombinant protein assays (Western blot, cell based, and protein screening array) confirmed antigen specificity.ResultsSerum and CSF from 6 patients produced identical synaptic immunoglobulin G (IgG) staining patterns of synaptic regions (neuropil) of the mouse cerebrum and cerebellum. The molecular layer of the cerebellum and the thalamus demonstrated stronger immunoreactivity than the midbrain, hippocampus, cortex, and basal ganglia. The antigen revealed by mass spectrometry analysis of immunoprecipitated cerebellar proteins and confirmed by recombinant protein assays was septin-5. All 4 patients with records available had subacute onset of cerebellar ataxia with prominent eye movement symptoms (oscillopsia or vertigo). None had cancer detected. Improvements occurred after immunotherapies (2) or spontaneously (1). One patient died.ConclusionSeptin-5 IgG represents a biomarker for a potentially fatal but treatable autoimmune ataxia.

Aphasia in Progressive Supranuclear Palsy: As Severe as Progressive Non-Fluent Aphasia.

Adynamic speech is characteristic of progressive supranuclear palsy (PSP), but higher language deficits have been reported inconsistently, in the context of clinical and pathological overlaps with progressive non-fluent aphasia (PNFA). The present study tested two hypotheses: 1) PSP and PNFA display impaired single word repetition, object naming, semantic knowledge, and syntactic comprehension; and 2) PSP have reduced speed on timed cognitive tasks. Structured clinical and neuropsychological assessments of language were performed on patients with clinically defined PSP and PNFA. Language was tested using the Sydney Language Battery (SYDBAT) and the Test of Reception of Grammar (TROG). In total, 144 participants were studied (PSP 22, PNFA 29, and Control 93). PSP patients had prominent eye movement abnormalities, parkinsonism, and falls. All 4 PSP patients who underwent postmortem examination had 4-Repeat tauopathy, with PSP pathology in 3. The frequency and severity of impairment on the SYDBAT (naming, word comprehension, semantic association), and TROG (syntactic comprehension) did not differ between PSP and PNFA, but PSP were significantly slower on timed non-language cognitive tests. Tested formally, aphasia may be seen in PSP, with a severity similar to that seen in PNFA.

Effects of 4-aminopyridine on nystagmus and vestibulo-ocular reflex in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is a progressive neurodegenerative disorder with prominent eye movement deficits localizing to the cerebellum. We sought to determine if 4-aminopyridine (4-AP), which putatively enhances the precision of Purkinje neurons, could improve the disorders of eye movements and vestibular function in A-T. The influence of 4-AP on disorders of eye movements and vestibular function was studied in four A-T patients. The effects on the cerebellar control of vestibulo-ocular reflex (VOR) was quantitatively assessed by the decay time constant of per- and post-rotational nystagmus during constant velocity en bloc rotations. The length of the VOR time constant determines the fidelity of the vestibular velocity storage, a neural mechanism that increases the bandwidth of VOR under cerebellar control. The VOR time constant was not increased in A-T patients. The latter is explained by the extent of cerebellar lesion as previously described in A-T and other cerebellar disorders. Nevertheless, 4-AP shortened the VOR time constant during horizontal rotations. Severe disinhibition of velocity storage in subjects with putatively profound cerebellar degeneration manifest periodic alternating nystagmus (PAN). Among two A-T subjects who manifested PAN, 4-AP reduced the peak slow phase velocity of the more severely affected individual and abrogated the PAN in the other. Two A-T subjects manifested horizontal and vertical spontaneous nystagmus (SN) in primary gaze, 4-AP reduced its slow phase velocity. We conclude that in subjects with A-T 4-AP has a prominent effect on the ocular motor and vestibular deficits that are ascribed to the loss of cerebellar Purkinje neurons.

Antidepressant Medications, Neuroleptics, and Prominent Eye Movements During NREM Sleep

Eye movements during stage 2, 3, and 4 sleep have been associated with the use of several selective serotonin reuptake inhibitor (SSRI) medications. This activity has been postulated to be a serotonin effect. The authors identified all cases of nonrapid eye movement (NREM) eye movements observed over a 36-month period in an accredited hospital-based sleep center and then correlated the findings with the patient's medications. The polysomnogram (PSG) studies of 2,959 consecutive adults were evaluated prospectively to identify all patients with atypical eye movements which occurred during NREM sleep. Standard recording, staging and arousal scoring methods were used. The use of antidepressants and neuroleptic medications was recorded for each patient. Eye movements in NREM sleep were detected in 94 PSGs. Of these, 73 patients (78%) were taking a SSRI at the time of the study, and 6 (6%) had taken a SSRI in the past. Thirty-six percent of patients (73 of 201) taking a SSRI had abnormal NREM eye movements on PSG. Other classes of antidepressants, neuroleptics, and benzodiazepines showed a much lower incidence of NREM eye movements. Mirtazapine was rarely related to NREM eye movements. Clonazepam and zolpidem were not associated with atypical eye movements unless used in combination with SSRI medications. Selective serotonin reuptake inhibitors was associated with atypical NREM eye movements, even when the medication had been discontinued months to years before the PSG. Atypical NREM eye movements appear to be related primarily to serotonin and less prominently to dopaminergic medication effects.

Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer's disease

Frontotemporal lobar degeneration (FTLD) often overlaps clinically with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), both of which have prominent eye movement abnormalities. To investigate the ability of oculomotor performance to differentiate between FTLD, Alzheimer's disease, CBS and PSP, saccades and smooth pursuit were measured in three FTLD subtypes, including 24 individuals with frontotemporal dementia (FTD), 19 with semantic dementia (SD) and six with progressive non-fluent aphasia (PA), as compared to 28 individuals with Alzheimer's disease, 15 with CBS, 10 with PSP and 27 control subjects. Different combinations of oculomotor abnormalities were identified in all clinical syndromes except for SD, which had oculomotor performance that was indistinguishable from age-matched controls. Only PSP patients displayed abnormalities in saccade velocity, whereas abnormalities in saccade gain were observed in PSP > CBS > Alzheimer's disease subjects. All patient groups except those with SD were impaired on the anti-saccade task, however only the FTLD subjects and not Alzheimer's disease, CBS or PSP groups, were able to spontaneously self-correct anti-saccade errors as well as controls. Receiver operating characteristic statistics demonstrated that oculomotor findings were superior to neuropsychological tests in differentiating PSP from other disorders, and comparable to neuropsychological tests in differentiating the other patient groups. These data suggest that oculomotor assessment may aid in the diagnosis of FTLD and related disorders.

Violent Dreaming and Antidepressant Drugs: or How Paroxetine Made Me Dream That I Was Fighting Saddam Hussein

Violent Dreaming and Antidepressant Drugs: or How Paroxetine Made Me Dream That I Was Fighting Saddam Hussein

Are the eye movements of dreaming sleep related to the visual images of the dreams?

ABSTRACTAs a result of recording eye movements during Stage REM sleep by AC electrooculography (EOG) previous investigators concluded that each eye movement is the response to the visual action in each dream. When we repeated the study using DC EOG it was discovered that only a minority of eye movements during Stage REM are in the direction of the visual action in the dream. If only single, large amplitude, prominent eye movements are considered then most such movements are related to colorful, compelling visual action occurring as a prominent single visual action against a quiet background. The AC recording method used in past studies emphasizes these isolated movements; perhaps this explains the disparity in results. At any rate, most eye movements during REM sleep are unrelated to the action in the dream. When these eye movements were analyzed in regard to the direction of movements, sequential order of movements, and randomness in time, we found that similar patterns of oculomotor output were found in all subjects. Thus, the nervous system executes a patterned output of oculomotor activity during dreaming sleep which is fairly consistent in all subjects. At times, however, a link is established between the visual and oculomotor systems and the eyes respond to visual action.