Signe Bray

A quantitative comparison of NIRS and fMRI across multiple cognitive tasks

Near infrared spectroscopy (NIRS) is an increasingly popular technology for studying brain function. NIRS presents several advantages relative to functional magnetic resonance imaging (fMRI), such as measurement of concentration changes in both oxygenated and deoxygenated hemoglobin, finer temporal resolution, and ease of administration, as well as disadvantages, most prominently inferior spatial resolution and decreased signal-to-noise ratio (SNR). While fMRI has become the gold standard for in vivo imaging of the human brain, in practice NIRS is a more convenient and less expensive technology than fMRI. It is therefore of interest to many researchers how NIRS compares to fMRI in studies of brain function. In the present study we scanned participants with simultaneous NIRS and fMRI on a battery of cognitive tasks, placing NIRS probes over both frontal and parietal brain regions. We performed detailed comparisons of the signals in both temporal and spatial domains. We found that NIRS signals have significantly weaker SNR, but are nonetheless often highly correlated with fMRI measurements. Both SNR and the distance between the scalp and the brain contributed to variability in the NIRS/fMRI correlations. In the spatial domain, we found that a photon path forming an ellipse between the NIRS emitter and detector correlated most strongly with the BOLD response. Taken together these findings suggest that, while NIRS can be an appropriate substitute for fMRI for studying brain activity related to cognitive tasks, care should be taken when designing studies with NIRS to ensure that: 1) the spatial resolution is adequate for answering the question of interest and 2) the design accounts for weaker SNR, especially in brain regions more distal from the scalp.

Functional near infrared spectroscopy (NIRS) signal improvement based on negative correlation between oxygenated and deoxygenated hemoglobin dynamics

Near infrared spectroscopy (NIRS) is a promising technology for functional brain imaging which measures hemodynamic signals from the cortex, similar to functional magnetic resonance imaging (fMRI), but does not require the participant to lie motionless in a confined space. NIRS can therefore be used for more naturalistic experiments, including face to face communication, or natural body movements, and is well suited for real-time applications that may require lengthy training. However, improving signal quality and reducing noise, especially noise induced by head motion, is challenging, particularly for real time applications. Here we study the properties of head motion induced noise, and find that motion noise causes the measured oxygenated and deoxygenated hemoglobin signals, which are typically strongly negatively correlated, to become more positively correlated. Next, we develop a method to reduce noise based on the principle that the concentration changes of oxygenated and deoxygenated hemoglobin should be negatively correlated. We show that despite its simplicity, this method is effective in reducing noise and improving signal quality, for both online and offline noise reduction.

Reduced Intrinsic Connectivity of Amygdala in Adults with Major Depressive Disorder

Imaging studies of major depressive disorder (MDD) have demonstrated enhanced resting-state activity of the amygdala as well as exaggerated reactivity to negative emotional stimuli relative to healthy controls (HCs). However, the abnormalities in the intrinsic connectivity of the amygdala in MDD still remain unclear. As the resting-state activity and functional connectivity (RSFC) reflect fundamental brain processes, we compared the RSFC of the amygdala between unmedicated MDD patients and HCs. Seventy-four subjects, 55 adults meeting the DSM-IV criteria for MDD and 19 HCs, underwent a resting-state 3-T functional magnetic resonance imaging scan. An amygdala seed-based low frequency RSFC map for the whole brain was generated for each group. Compared with HCs, MDD patients showed a wide-spread reduction in the intrinsic connectivity of the amygdala with a variety of brain regions involved in emotional processing and regulation, including the ventrolateral prefrontal cortex, insula, caudate, middle and superior temporal regions, occipital cortex, and cerebellum, as well as increased connectivity with the bilateral temporal poles (p < 0.05 corrected). The increase in the intrinsic connectivity of amygdala with the temporal poles was inversely correlated with symptom severity and anxiety scores. Although the directionality of connections between regions cannot be inferred from temporal correlations, the reduced intrinsic connectivity of the amygdala predominantly with regions involved in emotional processing may reflect impaired bottom-up signaling for top-down cortical modulation of limbic regions leading to abnormal affect regulation in MDD.

Applications of multivariate pattern classification analyses in developmental neuroimaging of healthy and clinical populations

Analyses of functional and structural imaging data typically involve testing hypotheses at each voxel in the brain. However, it is often the case that distributed spatial patterns may be a more appropriate metric for discriminating between conditions or groups. Multivariate pattern analysis has been gaining traction in neuroimaging of adult healthy and clinical populations; studies have shown that information present in neuroimaging data can be used to decode intentions and perceptual states, as well as discriminate between healthy and diseased brains. While few studies to date have applied these methods in pediatric populations, in this review we discuss exciting potential applications for studying both healthy, and aberrant, brain development. We include an overview of methods and discussion of challenges and limitations.

Aberrant frontal lobe maturation in adolescents with fragile X syndrome is related to delayed cognitive maturation

BACKGROUND Fragile X syndrome (FXS) is the most common known heritable cause of intellectual disability. Prior studies in FXS have observed a plateau in cognitive and adaptive behavioral development in early adolescence, suggesting that brain development in FXS may diverge from typical development during this period. METHODS In this study, we examined adolescent brain development using structural magnetic resonance imaging data acquired from 59 individuals with FXS and 83 typically developing control subjects aged 9 to 22, a subset of whom were followed up longitudinally (1-5 years; typically developing: 17, FXS: 19). Regional volumes were modeled to obtain estimates of age-related change. RESULTS We found that while structures such as the caudate showed consistent volume differences from control subjects across adolescence, prefrontal cortex (PFC) gyri showed significantly aberrant maturation. Furthermore, we found that PFC-related measures of cognitive functioning followed a similarly aberrant developmental trajectory in FXS. CONCLUSIONS Our findings suggest that aberrant maturation of the PFC during adolescence may contribute to persistent or increasing intellectual deficits in FXS.

Reduced Functional Connectivity during Working Memory in Turner Syndrome

Turner syndrome (TS) is a genetic disorder affecting females, resulting from the complete or partial absence of an X chromosome. The cognitive profile of TS shows relative strengths in the verbal domain and weaknesses in the procedural domain, including working memory. Neuroimaging studies have identified differences in the morphology of the parietal lobes, and white matter pathways linking frontal and parietal regions, as well as abnormal activation in dorsal frontal and parietal regions. Taken together these findings suggest that abnormal functional connectivity between frontal and parietal regions may be related to working memory impairments in TS, a hypothesis we tested in the present study. We scanned TS and typically developing participants with functional magnetic resonance imaging while they performed visuospatial and phonological working memory tasks. We generated a seed region in parietal cortex based on structural differences in TS and found that functional connectivity with dorsal frontal regions was reduced during working memory in TS. Finally, we found that connectivity was correlated with task performance in TS. These findings suggest that structural brain abnormalities in TS affect not only regional activity but also the functional interactions between regions and that this has important consequences for behavior.

Morphological Alterations in the Thalamus, Striatum, and Pallidum in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with cognitive, motor, and emotional symptoms. The thalamus and basal ganglia form circuits with the cortex supporting all three of these behavioral domains. Abnormalities in the structure of subcortical regions may suggest atypical development of these networks, with implications for understanding the neural basis of ASD symptoms. Findings from previous volumetric studies have been inconsistent. Here, using advanced surface-based methodology, we investigated localized differences in shape and surface area in the basal ganglia and thalamus in ASD, using T1-weighted anatomical images from the Autism Brain Imaging Data Exchange (373 male participants aged 7–35 years with ASD and 384 typically developing). We modeled effects of diagnosis, age, and their interaction on volume, shape, and surface area. In participants with ASD, we found expanded surface area in the right posterior thalamus corresponding to the pulvinar nucleus, and a more concave shape in the left mediodorsal nucleus. The shape of both caudal putamen and pallidum showed a relatively steeper increase in concavity with age in ASD. Within ASD participants, restricted, repetitive behaviors were positively associated with surface area in bilateral globus pallidus. We found no differences in overall volume, suggesting that surface-based approaches have greater sensitivity to detect localized differences in subcortical structure. This work adds to a growing body of literature implicating corticobasal ganglia-thalamic circuits in the pathophysiology of ASD. These circuits subserve a range of cognitive, emotional, and motor functions, and may have a broad role in the complex symptom profile in ASD.

Spatial and temporal functional connectivity changes between resting and attentive states

Remote brain regions show correlated spontaneous activity at rest within well described intrinsic connectivity networks (ICNs). Meta‐analytic coactivation studies have uncovered networks similar to resting ICNs, suggesting that in task states connectivity modulations may occur principally within ICNs. However, it has also been suggested that specific “hub” regions dynamically link networks under different task conditions. Here, we used functional magnetic resonance imaging at rest and a continuous visual attention task in 16 participants to investigate whether a shift from rest to attention was reflected by within‐network connectivity modulation, or changes in network topography. Our analyses revealed evidence for both modulation of connectivity within the default‐mode (DMN) and dorsal attention networks (DAN) between conditions, and identified a set of regions including the temporoparietal junction (TPJ) and posterior middle frontal gyrus (MFG) that switched between the DMN and DAN depending on the task. We further investigated the temporal nonstationarity of flexible (TPJ and MFG) regions during both attention and rest. This showed that moment‐to‐moment differences in connectivity at rest mirrored the variation in connectivity between tasks. Task‐dependent changes in functional connectivity of flexible regions may, therefore, be understood as shifts in the proportion of time specific connections are engaged, rather than a switch between networks per se. This ability of specific regions to dynamically link ICNs under different task conditions may play an important role in behavioral flexibility. Hum Brain Mapp 36:549–565, 2015.

Structural connectivity of visuotopic intraparietal sulcus.

The intraparietal sulcus (IPS) contains topographically organized regions, similar to retinotopic maps in visual cortex. These regions, referred to as IPS1-4, show similar functional responses to the mapping tasks used to define them, yet differing responses to tests of other posterior parietal cortex (PPC) functions such as short-term memory, eye movements and object viewing, suggesting that they may have distinct patterns of structural connectivity to other parts of the brain. The present study combined functional magnetic resonance imaging (fMRI) mapping with diffusion tensor imaging (DTI) to describe white matter connections of visuotopic regions along the IPS, in 25 neurotypical young-adult participants. We found that posterior IPS more likely connects to retinotopically defined visual regions, and superior temporal gyrus, relative to anterior IPS. Anterior IPS regions 3 and 4 had higher connection probabilities to prefrontal regions, relative to posterior IPS. All four IPS regions showed inter-hemispheric connections to analogous regions in the opposite hemisphere, as well as consistent connections to the thalamus and regions of the striatum. Multivariate pattern classification at the group level reliably distinguished IPS regions from one another on the basis of connectivity patterns, especially for the most distal pairs of regions; occipital and prefrontal regions provided the most discriminating information. These findings advance our understanding of the structure of visuotopic IPS, with implications for functional differences between regions, and possible homologies between humans and macaques. Visuospatial functions dependent on the parietal cortex are frequently impaired in individuals with developmental disorders and those afflicted by cerebrovascular disease; the findings described here can be used as a basis for comparing connectivity differences in these populations.

Neural network configuration and efficiency underlies individual differences in spatial orientation ability

Spatial orientation is a complex cognitive process requiring the integration of information processed in a distributed system of brain regions. Current models on the neural basis of spatial orientation are based primarily on the functional role of single brain regions, with limited understanding of how interaction among these brain regions relates to behavior. In this study, we investigated two sources of variability in the neural networks that support spatial orientation—network configuration and efficiency—and assessed whether variability in these topological properties relates to individual differences in orientation accuracy. Participants with higher accuracy were shown to express greater activity in the right supramarginal gyrus, the right precentral cortex, and the left hippocampus, over and above a core network engaged by the whole group. Additionally, high-performing individuals had increased levels of global efficiency within a resting-state network composed of brain regions engaged during orientation and increased levels of node centrality in the right supramarginal gyrus, the right primary motor cortex, and the left hippocampus. These results indicate that individual differences in the configuration of task-related networks and their efficiency measured at rest relate to the ability to spatially orient. Our findings advance systems neuroscience models of orientation and navigation by providing insight into the role of functional integration in shaping orientation behavior.