SOD1 and cognitive dysfunction in familial amyotrophic lateral sclerosis.

BACKGROUND: Sporadic Amyotrophic Lateral Sclerosis (sALS) is associated with frontotemporal dementia (ALS-FTD) or milder deficits of cognitive (predominantly executive) dysfunction (ALSCi) in some patients. Some forms of familial ALS (FALS) have a family history of FTD, ALS-FTD, or both, but there have been few reports of ALS-FTD in FALS patients with mutations of the gene superoxide dismutase-1 (SOD1 FALS). The aim of this study was to test the hypothesis that ALSCi may be found in non-SOD1 FALS, but that SOD1 FALS patients would show little or no evidence of cognitive change. METHODS: A neuropsychological test battery was administered to 41 SALS patients, 35 control participants, 7 FALS patients with a SOD1 mutation (SOD1 FALS) and 10 FALS patients without a SOD1 mutation (non-SOD1 FALS). RESULTS: Relative to control participants, non-SOD1 FALS patients had impaired performance on written verbal fluency and confrontation naming, and reported higher levels of executive behavioural problems. These deficits were absent in SOD1 FALS patients. SALS patients performed poorer than controls only on the Graded Naming Test. All ALS groups had higher levels of behavioural apathy and emotional lability than were found in control participants. Cognitive domains of memory, receptive language, and visuospatial perception were spared. Groups were matched for age, gender, premorbid full-scale IQ, anxiety and depression. DISCUSSION: Individuals with SOD1 gene mutations are less likely to have significant cognitive changes compared to non-SOD1 FALS patients. Cognitive abnormalities in ALS are heterogeneous and may reflect underlying genetic variations rather than a simple spectrum of extra-motor involvement.

Changes in memory for emotional material in amyotrophic lateral sclerosis (ALS).

The current study sought to examine the performance of non-demented ALS patients on neuropsychological tests involving emotional perception and memory. Nineteen non-demented patients with ALS were compared with 20 healthy controls on assessments of facial expression recognition, social judgement ratings of faces and recognition memory for emotional words. Patients and controls were well matched to exclude a range of potentially confounding variables. The patients and controls demonstrated significant differences on only one test of cognitive functioning. The ALS group demonstrated a failure to show the normative pattern of enhanced recognition memory for emotional words compared to neutral words and produced higher scores than controls on recognition memory for neutral words. These findings suggest that patients with ALS show a different pattern of cognitive performance with respect to memory for emotional material when compared to healthy adults.

Decision making in humans: the effect of manipulating the central noradrenergic system.

OBJECTIVES: Damasio has proposed an influential model of human decision making-the Somatic Marker Hypothesis (SMH), where he argues that somatic feedback to the brain influences decision making in humans. It is proposed that when choosing between options that differ in relative risk, a somatic marker (for example, a "gut feeling") feeds back to the brain and influences cognitive appraisal. This study tested the hypothesis that the noradrenergic system may play a part in this afferent feedback process. METHODS: Thirty healthy young adults were randomly allocated to receive placebo, 4 mg, or 8 mg reboxetine (a new selective noradrenergic reuptake inhibitor that acts to increase central noradrenergic activity). It is hypothesised that enhancement of central noradrenergic activity may amplify the effect of afferent feedback, and lead to altered decision making. All subjects completed the Iowa Gambling Task (IGT), a computerised card playing game where the player is instructed to try and win as much money as possible over 100 selections from one of four decks. RESULTS: There were no significant differences between the three groups in gambling task performance. CONCLUSION: This result suggests that central noradrenergic activity may not be critically involved in the afferent feedback mechanism that is central to the somatic marker hypothesis.

Dissociation of affective modulation of recollective and perceptual experience following amygdala damage.

It has been suggested that similar neural mechanisms may underlie the affective modulation of both recollective and perceptual experience. A case is reported of a patient who has bilateral amygdala damage and marked impairment in the perception of emotion, particularly fear. The patient DR and 10 healthy control subjects (matched for school leaving age, intelligence quotient, and non-emotional memory performance) were shown a series of slides accompanied by an emotionally arousing narrative. One week later DR and the controls were given a surprise memory test for this material. In addition, they completed a verbal memory test using emotionally arousing stimuli. Both DR and the healthy control subjects showed a normative pattern of enhanced memory for emotional material. On the basis of these results and the previously demonstrated impairment of perception of emotion in this patient, it is concluded that different neural mechanisms may underlie affective modulation of recollective and perceptual experience.