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Neuroimaging studies have identified multiple face-selective regions in human cortex but the functional division of labor between these regions is not yet clear. A central hypothesis, with some empirical support, is that face-selective regions in the superior temporal sulcus (STS) are particularly responsive to dynamic information in faces, whereas the fusiform face area (FFA) computes the static or invariant properties of faces. Here we directly tested this hypothesis by measuring the magnitude of response in each region to both dynamic and static stimuli. Consistent with the hypothesis, we found that the response to movies of faces was not significantly different from the response to static images of faces from these same movies in the right FFA and right occipital face area (OFA). By contrast the face-selective region in the right posterior STS (pSTS) responded nearly three times as strongly to dynamic faces as to static faces, and a face-selective region in the right anterior STS (aSTS) responded to dynamic faces only. Both of these regions also responded more strongly to moving faces than to moving bodies, indicating that they are preferentially engaged in processing dynamic information from faces, not in more general processing of any dynamic social stimuli. The response to dynamic and static faces was not significantly different in a third face-selective region in the posterior continuation of the STS (pcSTS). The strong selectivity of face-selective regions in the pSTS and aSTS, but not the FFA, OFA or pcSTS, for dynamic face information demonstrates a clear functional dissociation between different face-selective regions, and provides further clues into their function. ► The face-selective rpSTS region shows a strong preference for dynamic faces. ► The face-selective raSTS region responds to dynamic faces only. ► The rFFA and rOFA do not distinguish between dynamic and static faces.

Neuroimaging has revealed consistent activations in medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) extending to precuneus both during explicit self-reference tasks and during rest, a period during which some form of self-reference is assumed to occur in the default mode of brain function. The similarity between these two patterns of midline cortical activation may reflect a common neural system for explicit and default-mode self-reference, but there is little direct evidence about the similarities and differences between the neural systems that mediate explicit self-reference versus default-mode self-reference during rest. In two experiments, we compared directly the brain regions activated by explicit self-reference during judgments about trait adjectives and by rest conditions relative to a semantic task without self-reference. Explicit self-reference preferentially engaged dorsal MPFC, rest preferentially engaged precuneus, and both self-reference and rest commonly engaged ventral MPFC and PCC. These findings indicate that there are both associations (shared components) and dissociations between the neural systems underlying explicit self-reference and the default mode of brain function. ►Functional associations of self reference and default networks. ►Functional dissociations of self reference and default networks. ►Differential functional connectivity of self reference and default networks.

Reading about another person's beliefs engages 'Theory of Mind' processes and elicits highly reliable brain activation across individuals and experimental paradigms. Using functional magnetic resonance imaging, we examined activation during a story task designed to elicit Theory of Mind processing in a very large sample of neurotypical (N = 462) individuals, and a group of high-functioning individuals with autism spectrum disorders (N = 31), using both region-of-interest and whole-brain analyses. This large sample allowed us to investigate group differences in brain activation to Theory of Mind tasks with unusually high sensitivity. There were no differences between neurotypical participants and those diagnosed with autism spectrum disorder. These results imply that the social cognitive impairments typical of autism spectrum disorder can occur without measurable changes in the size, location or response magnitude of activity during explicit Theory of Mind tasks administered to adults.

Understanding the neurophysiology of human cognitive development relies on methods that enable accurate comparison of structural and functional neuroimaging data across brains from people of different ages. A fundamental question is whether the substantial brain growth and related changes in brain morphology that occur in early childhood permit valid comparisons of brain structure and function across ages. Here we investigated whether valid comparisons can be made in children from ages 4 to 11, and whether there are differences in the use of volume-based versus surface-based registration approaches for aligning structural landmarks across these ages. Regions corresponding to the calcarine sulcus, central sulcus, and Sylvian fissure in both the hemispheres were manually labeled on T1-weighted structural magnetic resonance images from 31 children ranging in age from 4.2 to 11.2years old. Quantitative measures of shape similarity and volumetric-overlap of these manually labeled regions were calculated when brains were aligned using a 12-parameter affine transform, SPM's nonlinear normalization, a diffeomorphic registration (ANTS), and FreeSurfer's surface-based registration. Registration error for normalization into a common reference framework across participants in this age range was lower than commonly used functional imaging resolutions. Surface-based registration provided significantly better alignment of cortical landmarks than volume-based registration. In addition, registering children's brains to a common space does not result in an age-associated bias between older and younger children, making it feasible to accurately compare structural properties and patterns of brain activation in children from ages 4 to 11. ►Brains of children between 4 and 11 years can be registered to a common space. ►Registration accuracy to common space does not show an age-associated bias. ►Increased accuracy using surface-based registration over volumetric approaches.

In functional magnetic resonance imaging (fMRI) studies, a cortical region in the right temporo-parietal junction (RTPJ) is recruited when participants read stories about people's thoughts ('Theory of Mind'). Both fMRI and lesion studies suggest that a region near the RTPJ is associated with attentional reorienting in response to an unexpected stimulus. Do Theory of Mind and attentional reorienting recruit a single population of neurons, or are there two neighboring but distinct neural populations in the RTPJ? One recent study compared these activations, and found evidence consistent with a single common region. However, the apparent overlap may have been due to the low resolution of the previous technique. We tested this hypothesis using a high-resolution protocol, within-subjects analyses, and more powerful statistical methods. Strict conjunction analyses revealed that the area of overlap was small and on the periphery of each activation. In addition, a bootstrap analysis identified a reliable 6-10 mm spatial displacement between the peak activations of the two tasks; the same magnitude and direction of displacement was observed in within-subjects comparisons. In all, these results suggest that there are neighboring but distinct regions within the RTPJ implicated in Theory of Mind and orienting attention.

The main objective of this study was to utilize high field (7T) in vivo proton magnetic resonance imaging to increase the ability to detect metabolite changes in people with ALS, specifically, to quantify levels of glutamine and glutamine separately. The second objective of this study was to correlate metabolic markers with clinical outcomes of disease progression. 13 ALS participants and 12 age-matched healthy controls (HC) underwent 7 Tesla MRI and MRS. Single voxel MR spectra were acquired from the left precentral gyrus using a very short echo time (TE = 5 ms) STEAM sequence. MRS data was quantified using LCModel and correlated to clinical outcome markers. N-acetylaspartate (NAA) and total NAA (tNA, NAA + NAAG) were decreased by 17% in people with ALS compared to HC (P = 0.004 and P = 0.005, respectively) indicating neuronal injury and/or loss in the precentral gyrus. tNA correlated with disease progression as measured by forced vital capacity (FVC) (P = 0.014; Rρ = 0.66) and tNA/tCr correlated with overall functional decline as measured by worsening of the ALS Functional Rating Scale-Revised (ALSFRS-R) (P = 0.004; Rρ = -0.74). These findings underscore the importance of NAA as a reliable biomarker for neuronal injury and disease progression in ALS. Glutamate (Glu) was 15% decreased in people with ALS compared to HC (P = 0.02) while glutamine (Gln) concentrations were similar between the two groups. Furthermore, the decrease in Glu correlated with the decrease in FVC (P = 0.013; Rρ = 0.66), a clinical marker of disease progression. The decrease in Glu is most likely driven by intracellular Glu loss due to neuronal loss and degeneration. Neither choline containing components (Cho), a marker for cell membrane turnover, nor myo-Inositol (mI), a suspected marker for neuroinflammation, showed significant differences between the two groups. However, mI/tNA was correlated with upper motor neuron burden (P = 0.004, Rρ = 0.74), which may reflect a relative increase of activated microglia around motor neurons. In summary, 7T 1H MRS is a powerful non-invasive imaging technique to study molecular changes related to neuronal injury and/or loss in people with ALS.

The rate of learning or memory formation varies over time for any individual, partly due to moment-to-moment fluctuation of brain state. Functional neuroimaging has revealed the neural correlates of learning and memory, but here we asked if neuroimaging can causally enhance human learning by detection of brain states that reveal when a person is prepared or not prepared to learn. The parahippocampal cortex (PHC) is essential for memory formation for scenes. Here, activation in PHC was monitored in real-time, and scene presentations were triggered when participants entered “good” or “bad” brain states for learning of novel scenes. Subsequent recognition memory was more accurate for scenes presented in “good” than “bad” brain states. These findings show that neuroimaging can identify in real-time brain states that enhance or depress learning and memory formation, and knowledge about such brain states may be useful for accelerating education and training. Further, the use of functional neuroimaging as a causal, rather than correlative, tool to study the human brain may open new insights into the neural basis of human cognition. ► Discovered human brain states of preparedness to learn new information. ► Used real-time fMRI of measured brain states to present new information. ► Controlled human learning by presenting information during good brain states. ► Transformed fMRI from a correlational to a causal method to study the human brain.

Although the neural systems supporting single word reading are well studied, there are limited direct comparisons between typical and dyslexic readers of the neural correlates of reading fluency. Reading fluency deficits are a persistent behavioral marker of dyslexia into adulthood. The current study identified the neural correlates of fluent reading in typical and dyslexic adult readers, using sentences presented in a word-by-word format in which single words were presented sequentially at fixed rates. Sentences were presented at slow, medium, and fast rates, and participants were asked to decide whether each sentence did or did not make sense semantically. As presentation rates increased, participants became less accurate and slower at making judgments, with comprehension accuracy decreasing disproportionately for dyslexic readers. In-scanner performance on the sentence task correlated significantly with standardized clinical measures of both reading fluency and phonological awareness. Both typical readers and readers with dyslexia exhibited widespread, bilateral increases in activation that corresponded to increases in presentation rate. Typical readers exhibited significantly larger gains in activation as a function of faster presentation rates than readers with dyslexia in several areas, including left prefrontal and left superior temporal regions associated with semantic retrieval and semantic and phonological representations. Group differences were more extensive when behavioral differences between conditions were equated across groups. These findings suggest a brain basis for impaired reading fluency in dyslexia, specifically a failure of brain regions involved in semantic retrieval and semantic and phonological representations to become fully engaged for comprehension at rapid reading rates.

Physiological noise dominates the SNR of the fMRI time-course at commonly used spatial resolutions at field strengths of 3 T and above. Operating in this physiological noise dominated regime limits some benefits of high field acquisition since increases in image SNR produce only modest increases in time-course SNR. Although previous studies have shown that the physiological noise dominance can be mitigated by using higher spatial resolutions, not all functional studies require voxel sizes smaller than the thickness of the human cortex. In this study, we examine the effect of acquiring high spatial resolution, thermal noise dominated time-courses and spatially smoothing the images to lower resolutions, which would otherwise be physiological noise dominated. At high field strengths, where physiological noise is most problematic, this strategy lowered the overall time-course variance compared to direct acquisition at commonly used spatial resolution. At 7 T for example, 5 × 5 × 3 mm 3 resolution images derived from smoothing 1.5 × 1.5 × 3 mm 3 data improved time-course SNR by a factor of 1.89 compared to a time-series acquired at 5 × 5 × 3 mm 3. Presumably, this effect was derived from the reduced physiological-to-thermal noise ratio in the high spatial resolution data followed by a smoothing operation that improves SNR without adding physiological noise. Our findings demonstrate that in contrast to conventional SNR penalties associated with spatially smoothing Fourier data, the time-course SNR of smoothed high-resolution data can be improved compared to direct acquisition at the desired resolution.

Social anxiety disorder–related alterations in basal ganglia regions, such as striatum and globus pallidus, though evident from metabolic imaging, remain to be explored using seed-based resting-state functional connectivity magnetic resonance imaging. Capitalizing on the enhanced sensitivity of a multichannel array coil, we collected high-resolution (2-mm isotropic) data from medication-naive patients and healthy control participants. Subcortical resting-state networks from structures including the striatum (caudate and putamen), globus pallidus, thalamus, amygdala, and periaqueductal gray were compared between the two groups. When compared with controls, the caudate seed revealed significantly higher functional connectivity (hyper-connectivity) in the patient group in medial frontal, prefrontal (anterior and dorsolateral), orbito-frontal, and anterior cingulate cortices, which are regions that are typically associated with emotional processing. In addition, with the putamen seed, the patient data exhibited increased connectivity in the fronto-parietal regions (executive control network) and subgenual cingulate (affective network). The globus pallidus seed showed significant increases in connectivity in the patient group, primarily in the precuneus, which is part of the default mode network. Significant hyper-connectivity in the precuneus, interior temporal, and parahippocampal cortices was also observed with the thalamus seed in the patient population, when compared with controls. With amygdala as seed region, between-group differences were primarily in supplementary motor area, inferior temporal gyrus, secondary visual cortex, angular gyrus, and cingulate gyrus. Seed from periaqueductal gray resulted in hyper-connectivity in the patient group, when compared with controls, in dorsolateral prefrontal cortex, precuneus, middle temporal gyrus, and inferior parietal lobule. In all the subcortical regions examined in this study, the control group did not have any significant enhancements in functional connectivity when compared with the patient group.