Reward deficits in behavioural variant frontotemporal dementia include insensitivity to negative stimuli.

During reward processing individuals weigh positive and negative features of a stimulus to determine whether they will pursue or avoid it. Though patients with behavioural variant frontotemporal dementia display changes in their pursuit of rewards, such as food, alcohol, money, and sex, the basis for these shifts is not clearly established. In particular, it is unknown whether patients' behaviour results from excessive focus on rewards, insensitivity to punishment, or to dysfunction in a particular stage of reward processing, such as anticipation, consumption, or action selection. Our goal was to determine the nature of the reward deficit in behavioural variant frontotemporal dementia and its underlying anatomy. We devised a series of tasks involving pleasant, unpleasant, and neutral olfactory stimuli, designed to separate distinct phases of reward processing. In a group of 25 patients with behavioural variant frontotemporal dementia and 21 control subjects, diagnosis by valence interactions revealed that patients with behavioural variant frontotemporal dementia rated unpleasant odours as less aversive than did controls and displayed lower skin conductance responses when anticipating an upcoming aversive odour. Subjective pleasantness ratings and skin conductance responses did not differ between behavioural variant frontotemporal dementia and controls for pleasant or neutral smells. In a task designed to measure the effort subjects would expend to smell or avoid smelling a stimulus, patients with behavioural variant frontotemporal dementia were less motivated, and therefore less successful than control subjects, at avoiding what they preferred not to smell, but had equivalent success at obtaining stimuli they found rewarding. Voxel-based morphometry of patients with behavioural variant frontotemporal dementia revealed that the inability to subjectively differentiate the valence of pleasant and unpleasant odours correlated with atrophy in right ventral mid-insula and right amygdala. High pleasantness ratings of unpleasant stimuli correlated with left dorsal anterior insula and frontal pole atrophy. These findings indicate that insensitivity to negative information may be a key component of the reward-seeking behaviours in behavioural variant frontotemporal dementia, and may relate to degeneration of structures that are involved in representing the emotional salience of sensory information.

Neuroeconomic dissociation of semantic dementia and behavioural variant frontotemporal dementia.

Many neuropsychiatric disorders are marked by abnormal behaviour and decision-making, but prevailing diagnostic criteria for such behaviours are typically qualitative and often ambiguous. Behavioural variant frontotemporal dementia and semantic variant primary progressive aphasia (also called semantic dementia) are two clinical variants of frontotemporal dementia with overlapping but distinct anatomical substrates known to cause profound changes in decision-making. We investigated whether abnormal decision-making in these syndromes could be more precisely characterized in terms of dissociable abnormalities in patients' subjective evaluations of valence (positive versus negative outcome) and of time (present versus future outcome). We presented 28 patients with behavioural variant frontotemporal dementia, 14 patients with semantic variant primary progressive aphasia, 25 patients with Alzheimer's disease (as disease controls), and 61 healthy older control subjects with experimental tasks assaying loss aversion and delay discounting. In general linear models controlling for age, gender, education and Mini-Mental State Examination score, patients with behavioural variant frontotemporal dementia were less averse to losses than control subjects (P < 0.001), while patients with semantic variant primary progressive aphasia discounted delayed rewards more steeply than controls (P = 0.019). There was no relationship between loss aversion and delay discounting across the sample, nor in any of the subgroups. These findings suggest that abnormal behaviours in neurodegenerative disease may result from the disruption of either of two dissociable neural processes for evaluating the outcomes of action. More broadly, these findings suggest a role for computational methods to supplement traditional qualitative characterizations in the differential diagnosis of neuropsychiatric disorders.

Executive functions in premanifest Huntington's disease.

BACKGROUND: We investigated the viability of psychometrically robust executive function measures as markers for premanifest Huntington's disease (HD). METHODS: Fifteen premanifest HD subjects and 42 controls were compared on the NIH EXAMINER executive function battery. This battery yields an overall executive composite score, plus working memory, cognitive control, and fluency scores that are measured on psychometrically matched scales. The scores were correlated with two disease markers, disease burden and striatal volumes, in the premanifest HD subjects. RESULTS: The premanifest HD subjects scored significantly lower on the working memory score. The executive composite positively correlated with striatal volumes, and the working memory score negatively correlated with disease burden. The cognitive control and fluency scores did not differ between the groups or correlate significantly with the disease markers. CONCLUSIONS: The NIH EXAMINER executive composite and working memory scores are sensitive markers of cognitive dysfunction, striatal volume, and disease burden in premanifest HD.

Ecological validity and neuroanatomical correlates of the NIH EXAMINER executive composite score.

Executive functions refer to a constellation of higher-level cognitive abilities that enable goal-oriented behavior. The NIH EXAMINER battery was designed to assess executive functions comprehensively and efficiently. Performance can be summarized by a single score, the "Executive Composite," which combines measures of inhibition, set-shifting, fluency, and working memory. We evaluated the ecological validity of the Executive Composite in a sample of 225 mixed neurological patients and controls using the Frontal Systems Behavior Scale (FrSBe), an informant-based measure of real-world executive behavior. In addition, we investigated the neuroanatomical correlates of the Executive Composite using voxel-based morphometry in a sample of 37 participants diagnosed with dementia, mild cognitive impairment, or as neurologically healthy. The Executive Composite accounted for 28% of the variance in Frontal Systems Behavior Scale scores beyond age. Even after including two widely used executive function tests (Trails B and Stroop) as covariates, the Executive Composite remained a significant predictor of real-world behavior. Anatomically, poorer scores on the Executive Composite were associated with smaller right and left dorsolateral prefrontal volumes, brain regions critical for good executive control. Taken together, these results suggest that the Executive Composite measures important aspects of executive function not captured by standard measures and reflects the integrity of frontal systems.

Black and White Young Adults' Support to Midlife Parents.

OBJECTIVES: Prior research suggests that midlife adults in Black and non-Hispanic White families differ in support patterns to aging parents. It is unclear whether such racial differences exist in young adulthood. We examined Black and White young adults' support to their midlife parents and underlying mechanisms to explain within-racial group, family-level differences. METHOD: Young adults (aged 18-30; Black n = 107 and White n = 351) from the Family Exchanges Study 2 reported how often they provided tangible (practical) and intangible (emotional support and advice) support to each parent. Participants also reported beliefs about obligation to support parents, rewards from helping, and parental needs. RESULTS: On average, Black young adults provided more tangible and intangible support than White young adults. Feelings of reward predicted why young adults in some Black and White families gave more support than those in other families. Parental needs explained tangible support in Black families and intangible support in White families. Within families, rewards and parental needs drove Black offspring to give more intangible support than their siblings, while obligation motivated White offspring. DISCUSSION: Consistent with support patterns evident in older adulthood, Black young adults gave more tangible and intangible support to their midlife parents compared to White young adults. Within-race support patterns were explained by different factors informed by the Multidimensional Intergenerational Support Model. Findings suggest psychological factors contribute to between- and within-racial patterns of exchanges.