Perception of Emotional Facial Expressions in Amyotrophic Lateral Sclerosis (ALS) at Behavioural and Brain Metabolic Level.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) primarily impairs motor abilities but also affects cognition and emotional processing. We hypothesise that subjective ratings of emotional stimuli depicting social interactions and facial expressions is changed in ALS. It was found that recognition of negative emotions and ability to mentalize other's intentions is reduced. METHODS: Processing of emotions in faces was investigated. A behavioural test of Ekman faces expressing six basic emotions was presented to 30 ALS patients and 29 age-, gender and education matched healthy controls. Additionally, a subgroup of 15 ALS patients that were able to lie supine in the scanner and 14 matched healthy controls viewed the Ekman faces during functional magnetic resonance imaging (fMRI). Affective state and a number of daily social contacts were measured. RESULTS: ALS patients recognized disgust and fear less accurately than healthy controls. In fMRI, reduced brain activity was seen in areas involved in processing of negative emotions replicating our previous results. During processing of sad faces, increased brain activity was seen in areas associated with social emotions in right inferior frontal gyrus and reduced activity in hippocampus bilaterally. No differences in brain activity were seen for any of the other emotional expressions. Inferior frontal gyrus activity for sad faces was associated with increased amount of social contacts of ALS patients. CONCLUSION: ALS patients showed decreased brain and behavioural responses in processing of disgust and fear and an altered brain response pattern for sadness. The negative consequences of neurodegenerative processes in the course of ALS might be counteracted by positive emotional activity and positive social interactions.

Additional resources and the default mode network: Evidence of increased connectivity and decreased white matter integrity in amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS), cognition is affected. Cortical atrophy in frontal and temporal areas has been associated with the cognitive profile of patients. Additionally, reduced metabolic turnover and regional cerebral blood flow in frontal areas indicative of reduced neural activity have been reported for ALS. We hypothesize that functional connectivity in non-task associated functional default mode network (DMN) is associated with cognitive profile and white matter integrity. This study focused on specific cognitive tasks known to be impaired in ALS such as verbal fluency and attention, and the relationship with functional connectivity in the DMN and white matter integrity. Nine patients and 11 controls were measured with an extensive neuropsychological battery. Resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were acquired. Results showed that ALS patients performed significantly worse in attention and verbal fluency task. Patients showed increased functional connectivity in parahippocampal and parietal areas of the non-task associated DMN compared to controls. The more pronounced the cognitive deficits, the stronger the increase in functional connectivity in those areas. White matter integrity was reduced in frontal areas in the patients. In conclusion, increased connectivity in the DMN in parahippocampal and parietal areas might represent recruitment of accessory brain regions to compensate for dysfunctional frontal networks.

Do eye movement impairments in patients with small vessel cerebrovascular disease depend on lesion load or on cognitive deficits? A video-oculographic and MRI study.

Small vessel cerebrovascular disease (SVCD) is one of the most frequent vessel disorders in the aged brain. Among the spectrum of neurological disturbances related to SVCD, oculomotor dysfunction is a not well understood symptom- in particular, it remains unclear whether vascular lesion load in specific brain regions affects oculomotor function independent of cognitive decline in SVCD patients or whether the effect of higher brain function deficits prevails. In this study, we examined a cohort of 25 SVCD patients and 19 healthy controls using video-oculographic eye movement recording in a laboratory environment, computer-based MRI assessment of white matter lesion load (WMLL), assessment of extrapyramidal motor deficits, and psychometric testing. In comparison to controls, the mean WMLL of patients was significantly larger than in controls. With respect to eye movement control, patients performed significantly worse than controls in almost all aspects of oculomotion. Likewise, patients showed a significantly worse performance in all but one of the neuropsychological tests. Oculomotor deficits in SVCD correlated with the patients' cognitive dysfunctioning while there was only weak evidence for a direct effect of WMLL on eye movement control. In conclusion, oculomotor impairment in SVCD seems to be mainly contingent upon cognitive deterioration in SVCD while WMLL might have only a minor specific effect upon oculomotor pathways.

Live and let die: existential decision processes in a fatal disease.

Decisions and determinants of decisions to prolong or shorten life in the course of fatal diseases like ALS are poorly understood. Decisions and desire for hastened death of N = 93 ALS patients were investigated in a prospective longitudinal approach three times in the course of 1 year. Determinants of decisions were evaluated: quality of life (QoL), depression, feeling of being a burden, physical function, social support and cognitive status. More than half of patients had a positive attitude towards life-sustaining treatments and they had a low desire for hastened death. Of those with undecided or negative attitude, 10 % changed attitudes towards life-sustaining treatments in the course of 1 year. Patients' desire to hasten death was low and decreased significantly within 1 year despite physical function decline. Those with a high desire for hastened death decided against invasive therapeutic treatments. QoL, depression and social support were not predictors for vital decisions and remained stable. Feeling of being a burden was a predictor for decisions against life-supporting treatments. Throughout physical function loss, decisions to prolong life are flexibly adapted while desire to shorten life declines. QoL was stable and not a predictor for vital decisions, even though anticipated low QoL has been reported to be the reason to request euthanasia. In contrast, feeling of being a burden in decision making needs more attention in clinical counselling. Considering a patient's possible adaptation processes in the course of a fatal disease is necessary.

Quality of life in fatal disease: the flawed judgement of the social environment.

Decisions to prolong or shorten life in fatal diseases like amyotrophic lateral sclerosis are strongly influenced by healthy individuals, such as caregivers and physicians. Furthermore, many believe that amyotrophic lateral sclerosis (ALS) patients should decide ahead of time on advanced directives to circumvent confounding effects of subsequent cognitive impairments. The ability of healthy persons (caregivers and age-matched healthy subjects) to anticipate patients' quality of life (QoL), depression and vital decisions was determined in a cross-sectional approach. Eighty-nine ALS patients, 86 caregivers and 102 age-matched healthy subjects were asked to judge ALS patients' QoL and depression and the patients' wish for hastened death. Patients judged their own, the caregivers judged that of the patient under their care, healthy subjects were asked to judge that of a virtual patient. Additionally, healthy persons were asked to judge their own QoL and depression. Patients reported a satisfactory well-being and a low wish for hastened death. Healthy persons rated the patients' QoL significantly lower and the rate of depression significantly higher. The wish for hastened death was significantly lower in the patient group compared to what healthy subjects thought the patient would wish. The assessment by others was closely related to the persons' own well-being. Significant differences were identified between caregiver's perspectives and the patient's own perception of their psychological well-being. Our data suggest that caregivers and the general public significantly underestimate the QoL of ALS patients. A positive affective state can indeed be preserved in a progressive, fatal disease.

Eye movement impairments in Parkinson's disease: possible role of extradopaminergic mechanisms.

BACKGROUND: The basal ganglia (BG) are thought to play an important role in the control of eye movements. Accordingly, the broad variety of subtle oculomotor alterations that has been described in Parkinson's disease (PD) are generally attributed to the dysfunction of the BG dopaminergic system. However, the present study suggest that dopamine substitution is much less effective in improving oculomotor performance than it is in restoring skeletomotor abilities. METHODS: We investigated reactive, visually guided saccades (RS), smooth pursuit eye movements (SPEM), and rapidly left-right alternating voluntary gaze shifts (AVGS) by video-oculography in 34 PD patients receiving oral dopaminergic medication (PD-DA), 14 patients with deep brain stimulation of the nucleus subthalamicus (DBS-STN), and 23 control subjects (CTL);In addition, we performed a thorough review of recent literature according therapeuthic effects on oculomotor performance in PD by switching deep brain stimulation off and on in the PD-DBS patients, we achieved swift changes between their therapeutic states without the delays of dopamine withdrawal. In addition, participants underwent neuropsychological testing. RESULTS: Patients exhibited the well known deficits such as increased saccade latency, reduced SPEM gain, and reduced frequency and amplitude of AVGS. Across patients none of the investigated oculomotor parameters correlated with UPDRS III whereas there was a negative correlation between SPEM gain and susceptibility to interference (Stroop score). Of the observed deficiencies, DBS-STN slightly improved AVGS frequency but neither AVGS amplitude nor SPEM or RS performance. CONCLUSIONS: We conclude that the impairment of SPEM in PD results from a cortical, conceivably non-dopaminergic dysfunction, whereas patients' difficulty to rapidly execute AVGS might be related to their BG dysfunction.

Deep brain stimulation and behavioural changes: is comedication the most important factor?

BACKGROUND: Adverse effects of dopaminergic medication (DA; levodopa and dopamine agonists) on impulsive behaviour and decision-making in patients with Parkinson's disease (PD) have been repeatedly reported. Deep brain stimulation (DBS) is increasingly used for the treatment of parkinsonian motor symptoms, but the excellent efficacy of DBS contrasts with a growing number of reports that the treatment may result in behavioural complications. AIMS: We investigated impulsive behaviour under different therapeutic treatments. METHODS: Fifteen patients with PD with DBS (PD-DBS) were assessed with electrical stimulation switched on and off, respectively. Data were compared with those of 15 patients with PD without DBS implantation under DA medication (PD-DA), matched for age and disease duration. Impulsive behaviour (gambling performance) was measured together with neuropsychological assessments regarding depression, current mood and cognitive performance. RESULTS: PD-DA patients performed worse in the gambling task than DBS patients with electrical stimulation turned off. A significant interaction of performance and medication was observed. When DBS was turned on, the differences in performance were less pronounced. CONCLUSION: For gambling performance, the medication dose mainly explains differences in impulsive behaviour. Although DBS had a minor negative effect on impulsive behaviour, the positive effect of a reduced DA dosis after DBS might reduce impulse control abnormalities.