Amyotrophic lateral sclerosis (ALS) primarily affects motor and speech abilities. In addition, cognitive functions are impaired in a subset of patients. There is a need to establish an eye movement-based method of neuropsychological assessment suitable for severely physically impaired patients with ALS. Forty-eight ALS patients and thirty-two healthy controls matched for age, sex and education performed a hand and speech motor-free version of the Raven's coloured progressive matrices (CPM) and the D2-test which had been especially adapted for eye-tracking control. Data were compared to a classical motor-dependent paper-pencil version. The association of parameters of the eye-tracking and the paper-pencil version of the tests and the differences between and within groups were studied. Subjects presented similar results in the eye-tracking and the corresponding paper-pencil versions of the CPM and D2-test: a correlation between performance accuracy for the CPM was observed for ALS patients (p < 0.001) and controls (p < 0.001) and in the D2-test for controls (p = 0.048), whereas this correlation did not reach statistical significance for ALS patients (p = 0.096). ALS patients performed worse in the CPM than controls in the eye-tracking (p = 0.053) and the paper-pencil version (p = 0.042). Most importantly, eye-tracking versions of the CPM (p < 0.001) and the D2-test (p = 0.024) reliably distinguished between more and less cognitively impaired patients. Eye-tracking-based neuropsychological testing is a promising approach for assessing cognitive deficits in patients who are unable to speak or write such as patients with severe ALS.

The syndrome of pathological laughing and crying (PLC) is characterized by episodes of involuntary outbursts of emotional expression. Although this phenomenon has been referred to for over a century, a clear-cut clinical definition is still lacking, and underlying pathophysiological mechanisms are not well understood. In particular, it remains ill-defined which kind of stimuli-contextually appropriate or inappropriate-elicit episodes of PLC, and if the phenomenon is a result of a lack of inhibition from the frontal cortex ("top-down-theory") or due to an altered processing of sensory inputs at the brainstem level ("bottom-up-theory"). To address these questions, we studied ten amyotrophic lateral sclerosis (ALS) patients with PLC and ten controls matched for age, sex and education. Subjects were simultaneously exposed to either emotionally congruent or incongruent visual and auditory stimuli and were asked to rate pictures according to their emotional quality. Changes in physiological parameters (heart rate, galvanic skin response, activity of facial muscles) were recorded, and a standardized self-assessment lability score (CNS-LS) was determined. Patients were influenced in their rating behaviour in a negative direction by mood-incongruent music. Compared to controls, they were influenced by negative stimuli, i.e. they rated neutral pictures more negatively when listening to sad music. Patients rated significantly higher on the CNS-LS. In patients, changes of electromyographic activity of mimic muscles during different emotion-eliciting conditions were explained by frontal cortex dysfunction. We conclude that PLC is associated with altered emotional suggestibility and that it is preferentially elicited by mood-incongruent stimuli. In addition, physiological reactions as well as behavioural changes suggest that this phenomenon is primarily an expression of reduced inhibitory activity of the frontal cortex, since frontal dysfunction could explain changes in physiological parameters in the patient group. We consider these findings being important for the clinical interpretation of emotional reactions of ALS patients.