Altered resting-state dynamics in autism spectrum disorder: causal to the social impairment?

Autism spectrum disorder (ASD) is characterized by profound impairments in social abilities and by restricted interests and repetitive behaviors. Much work in the past decade has been dedicated to understanding the brain-bases of ASD, and in the context of resting-state functional connectivity fMRI in high-functioning adolescents and adults, the field has established a set of reliable findings: decreased cortico-cortical interactions among brain regions thought to be engaged in social processing, along with a simultaneous increase in thalamo-cortical and striato-cortical interactions. However, few studies have attempted to manipulate these altered patterns, leading to the question of whether such patterns are actually causally involved in producing the corresponding behavioral impairments. We discuss a few such recent attempts in the domains of fMRI neurofeedback and overt social interaction during scanning, and we conclude that the evidence of causal involvement is somewhat mixed. We highlight the potential role of the thalamus and striatum in ASD and emphasize the need for studies that directly compare scanning during multiple cognitive states in addition to the resting-state

Automatic affective dynamics: An activation–habituation model of affective assimilation and contrast

Abstract. Our modeling approach seeks to better understand the computational dynamics of the affective and cognitive systems. One experimental phenomenon open to such dynamical analysis is "affective priming "-- or the influence of a prior stimulus on subsequent affective processing. In this type of procedure, ‘assimilation priming ’ refers to when the response to the target is biased in favor of the prime, such as with brief or minimally attended primes. However, following long durations or highly attended primes, the response to the target is often biased against the prime, which is termed ‘contrast priming’. We present a neural dynamics model of affective priming in which this transition from assimilation to contrast occurs automatically as a result of habituation. Unlike response strategies, this transition is predicted to rise and fall in a gradual nonlinear manner as a function of prime duration. We confirmed this prediction with a speeded affect judgment task that manipulated the exposure duration of valenced images.

10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1); a multicentre randomised trial

BACKGROUND: If carotid artery narrowing remains asymptomatic (ie, has caused no recent stroke or other neurological symptoms), successful carotid endarterectomy (CEA) reduces stroke incidence for some years. We assessed the long-term effects of successful CEA. METHODS: Between 1993 and 2003, 3120 asymptomatic patients from 126 centres in 30 countries were allocated equally, by blinded minimised randomisation, to immediate CEA (median delay 1 month, IQR 0·3-2·5) or to indefinite deferral of any carotid procedure, and were followed up until death or for a median among survivors of 9 years (IQR 6-11). The primary outcomes were perioperative mortality and morbidity (death or stroke within 30 days) and non-perioperative stroke. Kaplan-Meier percentages and logrank p values are from intention-to-treat analyses. This study is registered, number ISRCTN26156392. FINDINGS: 1560 patients were allocated immediate CEA versus 1560 allocated deferral of any carotid procedure. The proportions operated on while still asymptomatic were 89·7% versus 4·8% at 1 year (and 92·1%vs 16·5% at 5 years). Perioperative risk of stroke or death within 30 days was 3·0% (95% CI 2·4-3·9; 26 non-disabling strokes plus 34 disabling or fatal perioperative events in 1979 CEAs). Excluding perioperative events and non-stroke mortality, stroke risks (immediate vs deferred CEA) were 4·1% versus 10·0% at 5 years (gain 5·9%, 95% CI 4·0-7·8) and 10·8% versus 16·9% at 10 years (gain 6·1%, 2·7-9·4); ratio of stroke incidence rates 0·54, 95% CI 0·43-0·68, p<0·0001. 62 versus 104 had a disabling or fatal stroke, and 37 versus 84 others had a non-disabling stroke. Combining perioperative events and strokes, net risks were 6·9% versus 10·9% at 5 years (gain 4·1%, 2·0-6·2) and 13·4% versus 17·9% at 10 years (gain 4·6%, 1·2-7·9). Medication was similar in both groups; throughout the study, most were on antithrombotic and antihypertensive therapy. Net benefits were significant both for those on lipid-lowering therapy and for those not, and both for men and for women up to 75 years of age at entry (although not for older patients). INTERPRETATION: Successful CEA for asymptomatic patients younger than 75 years of age reduces 10-year stroke risks. Half this reduction is in disabling or fatal strokes. Net benefit in future patients will depend on their risks from unoperated carotid lesions (which will be reduced by medication), on future surgical risks (which might differ from those in trials), and on whether life expectancy exceeds 10 years. FUNDING: UK Medical Research Council, BUPA Foundation, Stroke Association