Altered functional connectivity in lesional peduncular hallucinosis with REM sleep behavior disorder

Brainstem lesions causing peduncular hallucinosis (PH) produce vivid visual hallucinations occasionally accompanied by sleep disorders. Overlapping brainstem regions modulate visual pathways and REM sleep functions via gating of thalamocortical networks. A 66-year-old man with paroxysmal atrial fibrillation developed abrupt–onset complex visual hallucinations with preserved insight and violent dream enactment behavior. Brain MRI showed restricted diffusion in the left rostrodorsal pons suggestive of an acute ischemic stroke. REM sleep behavior disorder (RBD) was diagnosed on polysomnography. We investigated the integrity of ponto-geniculate-occipital circuits with seed-based resting-state functional connectivity MRI (rs-fcMRI) in this patient compared to 46 controls. Rs-fcMRI revealed significantly reduced functional connectivity between the lesion and lateral geniculate nuclei (LGN), and between LGN and visual association cortex compared to controls. Conversely, functional connectivity between brainstem and visual association cortex, and between visual association cortex and prefrontal cortex (PFC) was significantly increased in the patient. Focal damage to the rostrodorsal pons is sufficient to cause RBD and PH in humans, suggesting an overlapping mechanism in both syndromes. This lesion produced a pattern of altered functional connectivity consistent with disrupted visual cortex connectivity via de-afferentation of thalamocortical pathways

Masked priming and ERPs dissociate maturation of orthographic and semantic components of visual word recognition in children

This study examined the time-course of reading single words in children and adults using masked repetition priming and the recording of event-related potentials. The N250 and N400 repetition priming effects were used to characterize form- and meaning-level processing, respectively. Children had larger amplitude N250 effects than adults for both shorter and longer duration primes. Children did not differ from adults on the N400 effect. The difference on the N250 suggests that automaticity for form processing is still maturing in children relative to adults, while the lack of differentiation on the N400 effect suggests that meaning processing is relatively mature by late childhood. The overall similarity in the children's repetition priming effects to adults' effects is in line with theories of reading acquisition, according to which children rapidly transition to an orthographic strategy for fast access to semantic information from print.Ellison Medical FoundationF32HD06118

Gender Differences in Emotion Regulation: An fMRI Study of Cognitive Reappraisal

Despite strong popular conceptions of gender differences in emotionality and striking gender differences in the prevalence of disorders thought to involve emotion dysregulation, the literature on the neural bases of emotion regulation is nearly silent regarding gender differences (Gross, 2007; Ochsner & Gross, in press). The purpose of the present study was to address this gap in the literature. Using functional magnetic resonance imaging, we asked male and female participants to use a cognitive emotion regulation strategy (reappraisal) to down-regulate their emotional responses to negatively valenced pictures. Behaviorally, men and women evidenced comparable decreases in negative emotion experience. Neurally, however, gender differences emerged. Compared with women, men showed (a) lesser increases in prefrontal regions that are associated with reappraisal, (b) greater decreases in the amygdala, which is associated with emotional responding, and (c) lesser engagement of ventral striatal regions, which are associated with reward processing. We consider two non-competing explanations for these differences. First, men may expend less effort when using cognitive regulation, perhaps due to greater use of automatic emotion regulation. Second, women may use positive emotions in the service of reappraising negative emotions to a greater degree. We then consider the implications of gender differences in emotion regulation for understanding gender differences in emotional processing in general, and gender differences in affective disorders

Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression

Background Neuroimaging studies of patients with major depression have revealed abnormal intrinsic functional connectivity measured during the resting state in multiple distributed networks. However, it is unclear whether these findings reflect the state of major depression or reflect trait neurobiological underpinnings of risk for major depression. Methods We compared resting-state functional connectivity, measured with functional magnetic resonance imaging, between unaffected children of parents who had documented histories of major depression (at-risk, n = 27; 8–14 years of age) and age-matched children of parents with no lifetime history of depression (control subjects, n = 16). Results At-risk children exhibited hyperconnectivity between the default mode network and subgenual anterior cingulate cortex/orbital frontal cortex, and the magnitude of connectivity positively correlated with individual symptom scores. At-risk children also exhibited 1) hypoconnectivity within the cognitive control network, which also lacked the typical anticorrelation with the default mode network; 2) hypoconnectivity between left dorsolateral prefrontal cortex and subgenual anterior cingulate cortex; and 3) hyperconnectivity between the right amygdala and right inferior frontal gyrus, a key region for top-down modulation of emotion. Classification between at-risk children and control subjects based on resting-state connectivity yielded high accuracy with high sensitivity and specificity that was superior to clinical rating scales. Conclusions Children at familial risk for depression exhibited atypical functional connectivity in the default mode, cognitive control, and affective networks. Such task-independent functional brain measures of risk for depression in children could be used to promote early intervention to reduce the likelihood of developing depression

The development of emotion regulation: an fMRI study of cognitive reappraisal in children, adolescents and young adults

The ability to use cognitive reappraisal to regulate emotions is an adaptive skill in adulthood, but little is known about its development. Because reappraisal is thought to be supported by linearly developing prefrontal regions, one prediction is that reappraisal ability develops linearly. However, recent investigations into socio-emotional development suggest that there are non-linear patterns that uniquely affect adolescents. We compared older children (10–13), adolescents (14–17) and young adults (18–22) on a task that distinguishes negative emotional reactivity from reappraisal ability. Behaviorally, we observed no age differences in self-reported emotional reactivity, but linear and quadratic relationships between reappraisal ability and age. Neurally, we observed linear age-related increases in activation in the left ventrolateral prefrontal cortex, previously identified in adult reappraisal. We observed a quadratic pattern of activation with age in regions associated with social cognitive processes like mental state attribution (medial prefrontal cortex, posterior cingulate cortex, anterior temporal cortex). In these regions, we observed relatively lower reactivity-related activation in adolescents, but higher reappraisal-related activation. This suggests that (i) engagement of the cognitive control components of reappraisal increases linearly with age and (ii) adolescents may not normally recruit regions associated with mental state attribution, but (iii) this can be reversed with reappraisal instructions.National Science Foundation (U.S.) (Grant BCS-0224342

Anatomical connectivity patterns predict face selectivity in the fusiform gyrus

A fundamental assumption in neuroscience is that brain structure determines function. Accordingly, functionally distinct regions of cortex should be structurally distinct in their connections to other areas. We tested this hypothesis in relation to face selectivity in the fusiform gyrus. By using only structural connectivity, as measured through diffusion-weighted imaging, we were able to predict functional activation to faces in the fusiform gyrus. These predictions outperformed two control models and a standard group-average benchmark. The structure–function relationship discovered from the initial participants was highly robust in predicting activation in a second group of participants, despite differences in acquisition parameters and stimuli. This approach can thus reliably estimate activation in participants who cannot perform functional imaging tasks and is an alternative to group-activation maps. Additionally, we identified cortical regions whose connectivity was highly influential in predicting face selectivity within the fusiform, suggesting a possible mechanistic architecture underlying face processing in humans.United States. Public Health Service (DA023427)National Institute of Mental Health (U.S.) (F32 MH084488)National Eye Institute (T32 EY013935)Poitras FoundationSimons FoundationEllison Medical Foundatio

Connectivity precedes function in the development of the visual word form area

What determines the cortical location at which a given functionally specific region will arise in development? We tested the hypothesis that functionally specific regions develop in their characteristic locations because of pre-existing differences in the extrinsic connectivity of that region to the rest of the brain. We exploited the visual word form area (VWFA) as a test case, scanning children with diffusion and functional imaging at age 5, before they learned to read, and at age 8, after they learned to read. We found the VWFA developed functionally in this interval and that its location in a particular child at age 8 could be predicted from that child's connectivity fingerprints (but not functional responses) at age 5. These results suggest that early connectivity instructs the functional development of the VWFA, possibly reflecting a general mechanism of cortical development.National Institutes of Health (U.S.) (Grant F32HD079169)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Grant F32HD079169)National Institutes of Health (U.S.) (Grant R01HD067312)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Grant R01HD067312

Failure of Working Memory Training to Enhance Cognition or Intelligence

Fluid intelligence is important for successful functioning in the modern world, but much evidence suggests that fluid intelligence is largely immutable after childhood. Recently, however, researchers have reported gains in fluid intelligence after multiple sessions of adaptive working memory training in adults. The current study attempted to replicate and expand those results by administering a broad assessment of cognitive abilities and personality traits to young adults who underwent 20 sessions of an adaptive dual n-back working memory training program and comparing their post-training performance on those tests to a matched set of young adults who underwent 20 sessions of an adaptive attentional tracking program. Pre- and post-training measurements of fluid intelligence, standardized intelligence tests, speed of processing, reading skills, and other tests of working memory were assessed. Both training groups exhibited substantial and specific improvements on the trained tasks that persisted for at least 6 months post-training, but no transfer of improvement was observed to any of the non-trained measurements when compared to a third untrained group serving as a passive control. These findings fail to support the idea that adaptive working memory training in healthy young adults enhances working memory capacity in non-trained tasks, fluid intelligence, or other measures of cognitive abilities.National Institutes of Health (U.S.) (Blueprint for Neuroscience Research (T90DA022759/R90DA023427)United States. Defense Advanced Research Projects Agency (government contract no. NBCHC070105)United States. Dept. of Defense (National Defense Science and Engineering Fellowship)Massachusetts Institute of Technology (Sheldon Razin (1959) Fellowship

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease