Functional and connectivity changes during working memory in Huntington’s disease: 18 month longitudinal data from the IMAGE-HD study

Background

This study aimed to characterize, for the first time, 18 month longitudinal changes in both functional activation and functional connectivity during working memory in premanifest Huntington’s disease (pre-HD) and symptomatic HD (symp-HD).

Methods

Functional magnetic resonance imaging (fMRI) was used to investigate longitudinal changes in neuronal activity during working memory performance via an N-BACK task (0-BACK and 1-BACK) in 27 pre-HD, 17 symp-HD, and 23 control participants. Whole-brain analysis of activation and region-of-interest analysis of functional connectivity was applied to longitudinal fMRI data collected at baseline and 18 months follow-up.

Results

Compared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK versus 0-BACK in the lateral and medial prefrontal, anterior cingulate, primary motor, and temporal areas cortically, and caudate and putamen subcortically. Pre-HD far from onset, compared with controls, showed further longitudinal increases in the right and left dorsolateral prefrontal cortex (DLPFC). Longitudinal increased activation in anterior cingulate and medial primary motor areas were associated with disease burden in the pre-HD group. Moreover, in pre-HD increased activation over time in primary motor and putamen regions were associated with average response time during 1-BACK performance. During 1-BACK, functional connectivity between the right DLPFC and posterior parietal, anterior cingulate, and caudate was significantly reduced over 18 months only in the pre-HD group.

Conclusions

Longitudinal reductions in connectivity over 18 months may represent an early signature of cortico-cortical and cortico-striatal functional disconnectivity in pre-HD, whereas the concomitant increased cortical and subcortical activation may reflect a compensatory response to the demands for cognitive resources required during task performance. Our findings demonstrate that functional imaging modalities have the potential to serve as sensitive methods for the assessment of cortical and subcortical responses to future treatment measures.     

Attentional capture by onsets and offsets

Three experiments were conducted to examine whether human infants would form a categorical representation for the spatial relation between. Experiment 1 showed that 6- and 7-month-olds familiarized with stimuli depicting a diamond in different locations between two reference bars subsequently preferred a stimulus displaying the diamond located outside the bars over a stimulus displaying the diamond located in a novel position between the bars. Experiments 2 and 3 revealed that this preference could not be attributed to a failure to discriminate the location changes of the diamond between the bars or an a priori preference. The overall pattern of results indicates that 6- and 7-month-olds had formed a categorical representation for between. The findings are discussed in terms of factors affecting development of categorical representations for spatial relation information.     

Evidence for a response preparation bottleneck during dual-task performance: Effect of a startling acoustic stimulus on the psychological refractory period

The present study was designed to investigate the mechanism associated with dual-task interference in a psychological refractory period (PRP) paradigm. We used a simple reaction time paradigm consisting of a vocal response (R1) and key-lift task (R2) with a stimulus onset asynchrony (SOA) between 100 ms and 1500 ms. On selected trials we implemented a startling acoustic stimulus concurrent with the second stimulus to determine if we could involuntarily trigger the second response. Our results indicated that the PRP delay in the second response was present for both control and startle trials at short SOAs, suggesting the second response was not prepared in advance. These results support a response preparation bottleneck and can be explained via a neural activation model of preparation. In addition, we found that the reflexive startle activation was reduced in the dual-task condition for all SOAs, a result we attribute to prepulse inhibition associated with dual-task processing.     

Effects of stress across the lifespan

Stress is a known precipitant for metabolic and neurological diseases, with sensitive periods identified across the developmental continuum from conception to old age. However, the effects of stress may vary depending on the point or points along the developmental trajectory when adversity strikes. Past research has emphasized the consequences of stress on fully developed physiological systems in the brain and periphery, but more recent studies have explored the impact of stress on systems at different stages of maturation, with differential effects being revealed. This review provides an overview of the diverse effects of stress at critical developmental stages and the potential outcomes that may be associated with experiencing environmental adversity during ontogeny.     

Serial color-word test predicts outcome of pharmacological treatment for panic disorder.

A group of 50 outpatients with Panic Disorder were given the Serial Color-Word Test at the beginning of a standard pharmacological treatment (selective serotonin reuptake inhibitors and benzodiazepines). A single treating psychiatrist, blind to test results, judged therapy outcome at a 5-mo. follow-up. Among the main types of adaptation to conflict assessed by the test (Stabilized, Cumulative, Dissociative, and Cumulative-Dissociative), the Stabilized pattern predicted a good therapy outcome. Response to therapy among the patients with a Stabilized pattern was judged as more often good and less often moderate or poor, compared with the members of the other three adaptation classes (p=.004), and specifically with the patients resorting to a Cumulative strategy (p=.005).     

Visual awareness and the on-line modification of action.

An influential theory of visually guided action proposes that (a) conscious perception of target displacement disrupts on-line action and (b) small target perturbations are inconsequential, provided the participant is unaware of them. This study examined these claims in a study of rapid aiming movements to targets. Novel features included on-line verbal reports of target displacement, and the factorial combination of small versus large displacements occurring near peak saccadic velocity or 100 ms later. Although awareness of target displacement had no effect on movement kinematics, even small target displacements near peak saccadic velocity affected kinematic measures. These results support both a strong view of visual stream separation in the on-line control of action and richer spatial coding by unconscious processes than has previously been acknowledged.     

Pain appraisal and quality of life in 108 outpatients with rheumatoid arthritis

Individual differences in emotional functioning, pain appraisal processing, and perceived social support may play a relevant role in the subjective experience of pain. Due to the paucity of data regarding individuals with Rheumatoid Arthritis (RA), the present study aimed to examine pain intensity, emotional functioning (psychological distress and alexithymia), pain appraisal (pain beliefs, pain catastrophizing, and pain-related coping strategies) and social support, and their relationships with the health-related quality of life (HRQoL) in patients with RA. Data were collected from 108 female patients diagnosed with RA. Clinically relevant levels of depressive and anxiety symptoms assessed by the HADS subscales were present in 34% and 41% of the patients, respectively, and about 24% of them exhibited the presence of alexithymia. The results of hierarchical multiple regression analyses showed that pain intensity, alexithymia, the maladaptive beliefs regarding the stability of pain and the coping strategy of guarding explained 54% of the variance in the physical component of HRQoL (p < 0.001). Depression subscale of the HADS, alexithymia, the coping strategy of resting, and the rumination factor of pain catastrophizing significantly explained 40% of the variance in the mental component of HRQoL (p < 0.001). The present findings provide evidence regarding the importance of emotional functioning and pain appraisal in the negative impact of RA on patients’ quality of life. These findings provide additional evidence for the biopsychosocial model of chronic pain, further supporting the complex interaction between emotional, cognitive, and behavioral processes in patients with chronic pain.