Cortical representations of phantom movements in lower limb amputees.

Understanding how sensorimotor cortex (SMC) organization relates to limb loss has major clinical implications, as cortical activity associated with phantom hand movements has been shown to predict phantom pain reports. Critically, earlier studies have largely focused on upper limb amputees; far less is known regarding SMC activity in lower limb amputees, despite the fact that this population comprises the majority of major limb loss cases. We aimed to characterize BOLD fMRI responses associated with phantom and sound limb movements to test the hypothesis that SMC organization is preserved in individuals with lower limb loss. Individuals with unilateral or bilateral lower limb loss underwent fMRI scans as they performed simple movements of their sound or phantom limbs. We observed that voluntary movements of the sound and phantom ankles were associated with BOLD signal changes in medial and superior portions of the precentral and postcentral gyri. In both hemispheres, contralateral limb movements were associated with greater signal changes compared to ipsilateral limb movements. Hand and mouth movements were associated with distinct activation patterns localized to more lateral SMC regions. We additionally tested whether activations associated with phantom movements related to self-report assessments indexing phantom pain experiences, nonpainful phantom sensations and phantom movement capabilities. We found that responses during phantom ankle movements did not correlate with any of the composite phantom limb indices in our sample. Our collective results reveal that SMC representations of the amputated limb persist and that traditional somatotopic organization is generally preserved in individuals suffering from lower limb loss.

Resting state functional MRI reveals abnormal network connectivity in neurofibromatosis 1.

Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the neurofibromin 1 gene at locus 17q11.2. Individuals with NF1 have an increased incidence of learning disabilities, attention deficits, and autism spectrum disorders. As a single-gene disorder, NF1 represents a valuable model for understanding gene-brain-behavior relationships. While mouse models have elucidated molecular and cellular mechanisms underlying learning deficits associated with this mutation, little is known about functional brain architecture in human subjects with NF1. To address this question, we used resting state functional connectivity magnetic resonance imaging (rs-fcMRI) to elucidate the intrinsic network structure of 30 NF1 participants compared with 30 healthy demographically matched controls during an eyes-open rs-fcMRI scan. Novel statistical methods were employed to quantify differences in local connectivity (edge strength) and modularity structure, in combination with traditional global graph theory applications. Our findings suggest that individuals with NF1 have reduced anterior-posterior connectivity, weaker bilateral edges, and altered modularity clustering relative to healthy controls. Further, edge strength and modular clustering indices were correlated with IQ and internalizing symptoms. These findings suggest that Ras signaling disruption may lead to abnormal functional brain connectivity; further investigation into the functional consequences of these alterations in both humans and in animal models is warranted.

Neural networks of colored sequence synesthesia.

Synesthesia is a condition in which normal stimuli can trigger anomalous associations. In this study, we exploit synesthesia to understand how the synesthetic experience can be explained by subtle changes in network properties. Of the many forms of synesthesia, we focus on colored sequence synesthesia, a form in which colors are associated with overlearned sequences, such as numbers and letters (graphemes). Previous studies have characterized synesthesia using resting-state connectivity or stimulus-driven analyses, but it remains unclear how network properties change as synesthetes move from one condition to another. To address this gap, we used functional MRI in humans to identify grapheme-specific brain regions, thereby constructing a functional "synesthetic" network. We then explored functional connectivity of color and grapheme regions during a synesthesia-inducing fMRI paradigm involving rest, auditory grapheme stimulation, and audiovisual grapheme stimulation. Using Markov networks to represent direct relationships between regions, we found that synesthetes had more connections during rest and auditory conditions. We then expanded the network space to include 90 anatomical regions, revealing that synesthetes tightly cluster in visual regions, whereas controls cluster in parietal and frontal regions. Together, these results suggest that synesthetes have increased connectivity between grapheme and color regions, and that synesthetes use visual regions to a greater extent than controls when presented with dynamic grapheme stimulation. These data suggest that synesthesia is better characterized by studying global network dynamics than by individual properties of a single brain region.

The genetics of colored sequence synesthesia: suggestive evidence of linkage to 16q and genetic heterogeneity for the condition.

Synesthesia is a perceptual condition in which sensory stimulation triggers anomalous sensory experiences. In colored sequence synesthesia (CSS), color experiences are triggered by sequences such as letters or numbers. We performed a family based linkage analysis to identify genetic loci responsible for the increased neural crosstalk underlying CSS. Our results implicate a 23 MB region at 16q12.2-23.1, providing the first step in understanding the molecular basis of CSS.