ImGo: A Novel Tool for Behavioral Impulsivity Assessment Based on Go/NoGo Tasks

This manuscript aims to present a novel behavioral impulsivity test ImGo, which is suitable for impulsivity assessment in the general population. A series of three studies was conducted to validate its psychometric qualities. In Study 1 we describe the principles of ImGo and verify its test-retest and split-half reliability and its convergent validity with an impulsivity self-report scale and Stop Signal test. In Study 2 we re-analyze the convergent validity of ImGo with a Stop Signal test and examine the potential relationship between ImGo and oculomotor inhibition measured by an Anti-Saccades test. In Study 3 we present a robust research with a large sample size and investigate the discriminant validity of ImGo with tests of other related cognitive and executive processes. Backed by our findings from these studies we can safely claim ImGo is a powerful tool with a good level of reliability (both test-retest and split-half) and validity (convergent and discriminant). Its potential lies in its use in diagnostic and research practice of experts from various countries as the test has already been translated to 9 languages so far. The open-source Hypothesis platform, on which the ImGo test is running, provides the option of both individual and group testing in laboratory conditions as well as remotely through an internet browser.

Preservation of eye movements in Parkinson’s disease is stimulus and task specific

Parkinson’s disease (PD) is a neurodegenerative disease that includes motor impairments such as tremor, bradykinesia, and postural instability. Although eye movement deficits are commonly found in saccade and pursuit tasks, preservation of oculomotor function has also been reported. Here we investigate specific task and stimulus conditions under which oculomotor function in PD is preserved. Sixteen PD patients and eighteen healthy, age-matched controls completed a battery of movement tasks that included stationary or moving targets eliciting reactive or deliberate eye movements: pro-saccades, anti-saccades, visually-guided pursuit, and rapid go/no-go manual interception. Compared to controls, patients demonstrated systematic impairments in tasks with stationary targets: pro-saccades were hypometric and anti-saccades were incorrectly initiated toward the cued target in about 35% of trials compared to 14% errors in controls. In patients, task errors were linked to short latency saccades, indicating abnormalities in inhibitory control. However, patients’ eye movements in response to dynamic targets were relatively preserved. PD patients were able to track and predict a disappearing moving target and make quick go/no-go decisions as accurately as controls. Patients’ interceptive hand movements were slower on average but initiated earlier, indicating adaptive processes to compensate for motor slowing. We conclude that PD patients demonstrate stimulus- and task-dependency of oculomotor impairments and propose that preservation of eye and hand movement function in PD is linked to a separate functional pathway through the SC-brainstem loop that bypasses the fronto-basal ganglia network.Significance StatementEye movements are a promising clinical tool to aid in the diagnosis of movement disorders and to monitor disease progression. Although Parkinson’s disease (PD) patients show some oculomotor abnormalities, it is not clear whether previously-described eye movement impairments are task specific. We assessed eye movements in PD under different visual (stationary vs. moving targets) and movement (reactive vs. deliberate) conditions. We demonstrate that PD patients are able to accurately track moving objects but make inaccurate eye movements towards stationary targets. The preservation of eye movements towards dynamic stimuli might enable patients to accurately act upon the predicted motion path of the moving target. These results can inform the development of tools for the rehabilitation or maintenance of functional performance.

Reflexive and Intentional Saccadic Eye Movements in Migraineurs

Background: Migraine has been postulated to lead to structural and functional changes of different cortical and subcortical areas, including the frontal lobe, the brainstem, and cerebellum. The (sub-)clinical impact of these changes is a matter of debate. The spectrum of possible clinical differences include domains such as cognition but also coordination. The present study investigated the oculomotor performance of patients with migraine with and without aura compared to control subjects without migraine in reflexive saccades, but also in intentional saccades, which involve cerebellar as well as cortical networks.Methods: In 18 patients with migraine with aura and 21 patients with migraine without aura saccadic eye movements were recorded in two reflexive (gap, overlap) and two intentional (anti, memory) paradigms and compared to 25 controls without migraine.Results: The main finding of the study was an increase of saccade latency in patients with and without aura compared to the control group solely in the anti-task. No deficits were found in the execution of reflexive saccades.Conclusions: Our results suggest a specific deficit in the generation of correct anti-saccades, such as vector inversion. Such processes are considered to need cortical networks to be executed correctly. The parietal cortex has been suggested to be involved in vector inversion processes but is not commonly described to be altered in migraine patients. It could be discussed that the cerebellum, which is recently thought to be involved in the pathophysiology of migraine, might be involved in distinct processes such as spatial re-mapping through known interconnections with parietal and frontal cortical areas.

Eye movement alterations in presymptomatic C9orf72 expansion gene carriers

Objective The clinical manifestation of amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration, whereas frontotemporal dementia (FTD) patients show alterations of behavior and cognition. Both share repeat expansions in C9orf72 as the most prevalent genetic cause. Before disease-defining symptoms onset, structural and functional changes at cortical level may emerge in C9orf72 carriers. Here, we characterized oculomotor parameters and their association to neuropsychological domains in apparently asymptomatic individuals with mutations in ALS/FTD genes. Patients and methods Forty-eight carriers of ALS genes, without any clinical symptoms underwent video-oculographic examination, including 22 subjects with C9orf72 mutation, 17 with SOD1, and 9 with other ALS associated gene mutations (n = 3 KIF5A; n = 3 FUS/FUS + TBK1; n = 1 NEK1; n = 1 SETX; n = 1 TDP43). A total of 17 subjects underwent a follow-up measurement. Data were compared to 54 age- and gender-matched healthy controls. Additionally, mutation carriers performed a neuropsychological assessment. Results In comparison to controls, the presymptomatic subjects performed significantly worse in executive oculomotor tasks such as the ability to perform correct anti-saccades. A gene mutation subgroup analysis showed that dysfunctions in C9orf72 carriers were much more pronounced than in SOD1 carriers. The anti-saccade error rate of ALS mutation carriers was associated with cognitive deficits: this correlation was increased in subjects with C9orf72 mutation, whereas SOD1 carriers showed no associations. Conclusion In C9orf72 carriers, executive eye movement dysfunctions, especially the increased anti-saccade error rate, were associated with cognitive impairment and unrelated to time. These oculomotor impairments are in support of developmental deficits in these mutations, especially in prefrontal areas.

Impaired Spatial Inhibition Processes for Interhemispheric Anti-saccades following Dorsal Posterior Parietal Lesions

Anti-saccades are eye movements that require inhibition to stop the automatic saccade to the visual target and to perform instead a saccade in the opposite direction. The inhibitory processes underlying anti-saccades have been primarily associated with frontal cortex areas for their role in executive control. Impaired performance in anti-saccades has also been associated with the parietal cortex, but its role in inhibitory processes remains unclear. Here, we tested the assumption that the dorsal parietal cortex contributes to spatial inhibition processes of contralateral visual target. We measured anti-saccade performance in 2 unilateral optic ataxia patients and 15 age-matched controls. Participants performed 90 degree (across and within visual fields) and 180 degree inversion anti-saccades, as well as pro-saccades. The main result was that our patients took longer to inhibit visually guided saccades when the visual target was presented in the ataxic hemifield and the task required a saccade across hemifields. This was observed through anti-saccades latencies and error rates. These deficits show the crucial role of the dorsal posterior parietal cortex in spatial inhibition of contralateral visual target representations to plan an accurate anti-saccade toward the ipsilesional side.

Cognitive Impairment and Diminished Neural Responses Constitute a Biomarker Signature of Negative Symptoms in Psychosis

The treatment of negative symptoms (NS) in psychosis represents an urgent unmet medical need given the significant functional impairment it contributes to psychosis syndromes. The lack of progress in treating NS is impacted by the lack of known pathophysiology or associated quantitative biomarkers, which could provide tools for research. This current analysis investigated potential associations between NS and an extensive battery of behavioral and brain-based biomarkers in 932 psychosis probands from the B-SNIP database. The current analyses examined associations between PANSS-defined NS and (1) cognition, (2) pro-/anti-saccades, (3) evoked and resting-state electroencephalography (EEG), (4) resting-state fMRI, and (5) tractography. Canonical correlation analyses yielded symptom-biomarker constructs separately for each biomarker modality. Biomarker modalities were integrated using canonical discriminant analysis to summarize the symptom-biomarker relationships into a “biomarker signature” for NS. Finally, distinct biomarker profiles for 2 NS domains (“diminished expression” vs “avolition/apathy”) were computed using step-wise linear regression. NS were associated with cognitive impairment, diminished EEG response amplitudes, deviant resting-state activity, and oculomotor abnormalities. While a connection between NS and poor cognition has been established, association to neurophysiology is novel, suggesting directions for future mechanistic studies. Each biomarker modality was related to NS in distinct and complex ways, giving NS a rich, interconnected fingerprint and suggesting that any one biomarker modality may not adequately capture the full spectrum of symptomology.