Development of deactivation of the default-mode network during episodic memory formation

Task-induced deactivation of the default-mode network (DMN) has been associated in adults with successful episodic memory formation, possibly as a mechanism to focus allocation of mental resources for successful encoding of external stimuli. We investigated developmental changes of deactivation of the DMN (posterior cingulate, medial prefrontal, and bilateral lateral parietal cortices) during episodic memory formation in children, adolescents, and young adults (ages 8–24), who studied scenes during functional magnetic resonance imaging (fMRI). Recognition memory improved with age. We defined DMN regions of interest from a different sample of participants with the same age range, using resting-state fMRI. In adults, there was greater deactivation of the DMN for scenes that were later remembered than scenes that were later forgotten. In children, deactivation of the default-network did not differ reliably between scenes that were later remembered or forgotten. Adolescents exhibited a pattern of activation intermediate to that of children and adults. The hippocampal region, often considered part of the DMN, showed a functional dissociation with the rest of the DMN by exhibiting increased activation for later remembered than later forgotten scene that was similar across age groups. These findings suggest that development of memory ability from childhood through adulthood may involve increased deactivation of the neocortical DMN during learning

Influence of Rhythmic Grouping on Duration Perception: A Novel Auditory Illusion

This study investigated a potential auditory illusion in duration perception induced by rhythmic temporal contexts. Listeners with or without musical training performed a duration discrimination task for a silent period in a rhythmic auditory sequence. The critical temporal interval was presented either within a perceptual group or between two perceptual groups. We report the just-noticeable difference (difference limen, DL) for temporal intervals and the point of subjective equality (PSE) derived from individual psychometric functions based on performance of a two-alternative forced choice task. In musically untrained individuals, equal temporal intervals were perceived as significantly longer when presented between perceptual groups than within a perceptual group (109.25% versus 102.5% of the standard duration). Only the perceived duration of the between-group interval was significantly longer than its objective duration. Musically trained individuals did not show this effect. However, in both musically trained and untrained individuals, the relative difference limens for discriminating the comparison interval from the standard interval were larger in the between-groups condition than in the within-group condition (7.3% vs. 5.6% of the standard duration). Thus, rhythmic grouping affected sensitivity to duration changes in all listeners, with duration differences being harder to detect at boundaries of rhythm groups than within rhythm groups. Our results show for the first time that temporal Gestalt induces auditory duration illusions in typical listeners, but that musical experts are not susceptible to this effect of rhythmic grouping.Ellison Medical FoundationNational Science Foundation (U.S.) (PA00P1_131448/1)McGovern Institute for Brain Research at MI

Neural fate of seen and unseen faces in visuospatial neglect: A combined event-related functional MRI and event-related potential study

This is a post print version of the article. The official published version can be obtained from the link below.To compare neural activity produced by visual events that escape or reach conscious awareness, we used event-related MRI and evoked potentials in a patient who had neglect and extinction after focal right parietal damage, but intact visual fields. This neurological disorder entails a loss of awareness for stimuli in the field contralateral to a brain lesion when stimuli are simultaneously presented on the ipsilateral side, even though early visual areas may be intact, and single contralateral stimuli may still be perceived. Functional MRI and event-related potential study were performed during a task where faces or shapes appeared in the right, left, or both fields. Unilateral stimuli produced normal responses in V1 and extrastriate areas. In bilateral events, left faces that were not perceived still activated right V1 and inferior temporal cortex and evoked nonsignificantly reduced N1 potentials, with preserved face-specific negative potentials at 170 ms. When left faces were perceived, the same stimuli produced greater activity in a distributed network of areas including right V1 and cuneus, bilateral fusiform gyri, and left parietal cortex. Also, effective connectivity between visual, parietal, and frontal areas increased during perception of faces. These results suggest that activity can occur in V1 and ventral temporal cortex without awareness, whereas coupling with dorsal parietal and frontal areas may be critical for such activity to afford conscious perception. Right parietal damage may cause a loss of awareness for contralateral (left) sensory inputs, such as hemispatial neglect and extinction (1–3). Visual extinction is the failure to perceive a stimulus in the contralesional field when presented together with an ipsilesional stimulus (bilateral simultaneous stimulation, BSS), even though occipital visual areas are intact and unilateral contralesional stimuli can be perceived when presented alone. It reflects a deficit of spatial attention toward the contralesional side, excluding left inputs from awareness in the presence of competing stimuli (2, 3). Spatial attention involves a complex neural network centered on the right parietal lobe (4, 5), but how parietal and related areas interact with sensory processing in distant cortices is largely unknown. Here we combined event-related functional MRI (fMRI) and event-related potentials (ERPs) to study the regional pattern and temporal course of brain activity produced by seen and unseen stimuli in a patient with chronic neglect and extinction caused by parietal damage. In keeping with intact early visual areas in such patients, behavioral studies suggest that some residual processing may still occur for contralesional stimuli without attention, or without awareness, including “preattentive” grouping (e.g., refs. 6 and 7) and semantic priming (e.g., ref. 8). It has been speculated (3, 9) that such effects might relate to separate cortical visual streams, with temporal areas extracting object features for identification, and parietal areas encoding spatial locations and parameters for action (10). Because neglect and extinction follow parietal damage, residual perceptual and semantic processing still might occur in occipital and temporal cortex without awareness, in the absence of normal integration with concomitant processing in parietal regions. Our study tested this hypothesis by using event-related imaging and electrophysiology measures, which are widely used to study mechanisms of normal attention (11, 12). There have been few imaging (e.g., ref. 13) or ERP (e.g., ref. 14) studies in neglect, and most examined activity at rest or during passive unilateral visual stimulation, rather than in relation to awareness or extinction on bilateral stimulation. However, a recent ERP study (15) found signals evoked by perceived, but not extinguished, visual stimuli in a parietal patient. By contrast, functional imaging in another patient (16) showed activation of striate cortex by extinguished stimuli, although severe extinction on all bilateral stimuli precluded any comparison with normal perception. In our patient we used both fMRI and ERPs during a similar extinction task to determine the neural correlates of two critical conditions: (i) when contralesional stimuli are extinguished, and (ii) when the same stimuli are seen. Stimulus presentation was arranged so as to obtain a balanced number of extinguished and seen contralesional events across all bilateral trials. Like Rees et al. (16), we used face stimuli to exploit previous knowledge that face processing activates fusiform areas in temporal cortex (e.g., refs. 17 and 18), and elicits characteristic potentials 170–200 ms after stimulus onset (e.g., refs. 19–21) in addition to other visual components such as P1 and N1 (e.g., ref. 11). We reasoned that such responses might help trace the neural fate of contralesional stimuli (seen or extinguished) at both early and later processing stages in the visual system

Neural correlates of emotion acceptance vs worry or suppression in generalized anxiety disorder

Recent emotion dysregulationmodels of generalized anxiety disorder (GAD) propose chronic worry in GAD functions as a maladaptive attempt to regulate anxiety related to uncertain or unpredictable outcomes. Emotion acceptance is an adaptive emotion regulation strategy increasingly incorporated into newer cognitive behavioral therapy (CBT) approaches to GAD to counter chronic worry. The current study explores themechanisms of emotion acceptance as an alternate emotion regulation strategy to worry or emotion suppression using functionalmagnetic resonance imaging. Twenty-one female participants diagnosed with GAD followed counterbalanced instructions to regulate responses to personally relevant worry statements by engaging in either emotion acceptance, worry or emotion suppression. Emotion acceptance resulted in lower ratings of distress than worry and was associated with increased dorsal anterior cingulate cortex (dACC) activation and increased ventrolateral prefrontal cortex (VLPFC)-amygdala functional connectivity. In contrast, worry showed significantly greater distress ratings than acceptance or suppression and was associated with increased precuneus, VLPFC, amygdala and hippocampal activation. Suppression did not significantly differ fromacceptance in distress ratings or amygdala recruitment, but resulted in significantly greater insula and VLPFC activation and decreased VLPFC-amygdala functional connectivity. Emotion acceptance closely aligned with activation and connectivity patterns reported in studies of contextual extinction learning and mindful awareness.National Institute of Mental Health (U.S.) (Grant F31 MH084422

Resting-state anticorrelations between medial and lateral prefrontal cortex: Association with working memory, aging, and individual differences

We examined how variation in working memory (WM) capacity due to aging or individual differences among young adults is associated with intrinsic or resting-state anticorrelations, particularly between (1) the medial prefrontal cortex (MPFC), a component of the default-mode network (DMN) that typically decreases in activation during external, attention-demanding tasks, and (2) the dorsolateral prefrontal cortex (DLPFC), a component of the fronto-parietal control network that supports executive functions and WM and typically increases in activation during attention-demanding tasks. We compared the magnitudes of MPFC-DLPFC anticorrelations between healthy younger and older participants (Experiment 1) and related the magnitudes of these anticorrelations to individual differences on two behavioral measures of WM capacity in two independent groups of young adults (Experiments 1 and 2). Relative to younger adults, older adults exhibited reductions in WM capacity and in MPFC-DLPFC anticorrelations. Within younger adults, greater MPFC-DLPFC anticorrelation at rest correlated with greater WM capacity. These findings show that variation in MPFC-DLPFC anticorrelations, whether related to aging or to individual differences, may reflect an intrinsic functional brain architecture supportive of WM capacity.National Institutes of Health (U.S.) (National Institute on Aging Grant R21 AG030770)National Institutes of Health (U.S.) (Grant T32 GM007484)Barbara J. Weedon Fund Fellowshi

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

Shared temporoparietal dysfunction in dyslexia and typical readers with discrepantly high IQ

It is currently believed that reading disability (RD) should be defined by reading level without regard to broader aptitude (IQ). There is debate, however, about how to classify individuals who read in the typical range but less well than would be expected by their higher IQ. We used functional magnetic resonance imaging (fMRI) in 49 children to examine whether those with typical reading ability, but discrepantly low relative to IQ, show dyslexia-like activation patterns during reading. Children who were typical readers with high-IQ discrepancy showed reduced activation in left temporoparietal neocortex relative to two control groups of typical readers without IQ discrepancy. This pattern was consistent and spatially overlapping with results in children with RD compared to typically reading children. The results suggest a shared neurological atypicality in regions associated with phonological processing between children with dyslexia and children having typical reading ability that is substantially below their IQ

Brain differences between persistent and remitted attention deficit hyperactivity disorder

Previous resting state studies examining the brain basis of attention deficit hyperactivity disorder have not distinguished between patients who persist versus those who remit from the diagnosis as adults. To characterize the neurobiological differences and similarities of persistence and remittance, we performed resting state functional magnetic resonance imaging in individuals who had been longitudinally and uniformly characterized as having or not having attention deficit hyperactivity disorder in childhood and again in adulthood (16 years after baseline assessment). Intrinsic functional brain organization was measured in patients who had a persistent diagnosis in childhood and adulthood (n = 13), in patients who met diagnosis in childhood but not in adulthood (n = 22), and in control participants who never had attention deficit hyperactivity disorder (n = 17). A positive functional correlation between posterior cingulate and medial prefrontal cortices, major components of the default-mode network, was reduced only in patients whose diagnosis persisted into adulthood. A negative functional correlation between medial and dorsolateral prefrontal cortices was reduced in both persistent and remitted patients. The neurobiological dissociation between the persistence and remittance of attention deficit hyperactivity disorder may provide a framework for the relation between the clinical diagnosis, which indicates the need for treatment, and additional deficits that are common, such as executive dysfunctions.McGovern Institute for Brain Research at MIT (Poitras Center for Affective Disorders Research)Massachusetts General Hospital (Paediatric Psychopharmacology Council Fund

Functional Brain Basis of Hypnotizability

Context Focused hypnotic concentration is a model for brain control over sensation and behavior. Pain and anxiety can be effectively alleviated by hypnotic suggestion, which modulates activity in brain regions associated with focused attention, but the specific neural network underlying this phenomenon is not known. Objective To investigate the brain basis of hypnotizability. Design Cross-sectional, in vivo neuroimaging study performed from November 2005 through July 2006. Setting Academic medical center at Stanford University School of Medicine. Patients Twelve adults with high and 12 adults with low hypnotizability. Main Outcome Measures Functional magnetic resonance imaging to measure functional connectivity networks at rest, including default-mode, salience, and executive-control networks; structural T1 magnetic resonance imaging to measure regional gray and white matter volumes; and diffusion tensor imaging to measure white matter microstructural integrity. Results High compared with low hypnotizable individuals had greater functional connectivity between the left dorsolateral prefrontal cortex, an executive-control region of the brain, and the salience network composed of the dorsal anterior cingulate cortex, anterior insula, amygdala, and ventral striatum, involved in detecting, integrating, and filtering relevant somatic, autonomic, and emotional information using independent component analysis. Seed-based analysis confirmed elevated functional coupling between the dorsal anterior cingulate cortex and the dorsolateral prefrontal cortex in high compared with low hypnotizable individuals. These functional differences were not due to any variation in brain structure in these regions, including regional gray and white matter volumes and white matter microstructure. Conclusions Our results provide novel evidence that altered functional connectivity in the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex may underlie hypnotizability. Future studies focusing on how these functional networks change and interact during hypnosis are warranted

Altered Resting-State Functional Connectivity of the Frontal-Striatal Reward System in Social Anxiety Disorder

We investigated differences in the intrinsic functional brain organization (functional connectivity) of the human reward system between healthy control participants and patients with social anxiety disorder. Functional connectivity was measured in the resting-state via functional magnetic resonance imaging (fMRI). 53 patients with social anxiety disorder and 33 healthy control participants underwent a 6-minute resting-state fMRI scan. Functional connectivity of the reward system was analyzed by calculating whole-brain temporal correlations with a bilateral nucleus accumbens seed and a ventromedial prefrontal cortex seed. Patients with social anxiety disorder, relative to the control group, had (1) decreased functional connectivity between the nucleus accumbens seed and other regions associated with reward, including ventromedial prefrontal cortex; (2) decreased functional connectivity between the ventromedial prefrontal cortex seed and lateral prefrontal regions, including the anterior and dorsolateral prefrontal cortices; and (3) increased functional connectivity between both the nucleus accumbens seed and the ventromedial prefrontal cortex seed with more posterior brain regions, including anterior cingulate cortex. Social anxiety disorder appears to be associated with widespread differences in the functional connectivity of the reward system, including markedly decreased functional connectivity between reward regions and between reward regions and lateral prefrontal cortices, and markedly increased functional connectivity between reward regions and posterior brain regions.Massachusetts Institute of Technology (Janet and Sheldon Razin Fellowship