@article {831, title = {Disruption of functional organization within the primary motor cortex in children with autism.}, journal = {Hum Brain Mapp}, volume = {35}, year = {2014}, month = {2014 Feb}, pages = {567-80}, abstract = {

Accumulating evidence suggests that motor impairments are prevalent in autism spectrum disorder (ASD), relate to the social and communicative deficits at the core of the diagnosis and may reflect abnormal connectivity within brain networks underlying motor control and learning. Parcellation of resting-state functional connectivity data using spectral clustering approaches has been shown to be an effective means of visualizing functional organization within the brain but has most commonly been applied to explorations of normal brain function. This article presents a parcellation of a key area of the motor network, the primary motor cortex (M1), a key area of the motor control network, in adults, typically developing (TD) children and children with ASD and introduces methods for selecting the number of parcels, matching parcels across groups and testing group differences. The parcellation is based solely on patterns of connectivity between individual M1 voxels and all voxels outside of M1, and within all groups, a gross dorsomedial to ventrolateral organization emerged within M1 which was left-right symmetric. Although this gross organizational scheme was present in both groups of children, statistically significant group differences in the size and segregation of M1 parcels within regions of the motor homunculus corresponding to the upper and lower limbs were observed. Qualitative comparison of the M1 parcellation for children with ASD with that of younger and older TD children suggests that these organizational differences, with a lack of differentiation between lower limb/trunk regions and upper limb/hand regions, may be due, at least in part, to a delay in functional specialization within the motor cortex.

}, keywords = {Adult, Autistic Disorder, brain mapping, Child, Developmental Disabilities, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Motor Cortex, Oxygen, Young Adult}, issn = {1097-0193}, doi = {10.1002/hbm.22188}, author = {Nebel, Mary Beth and Joel, Suresh E and Muschelli, John and Barber, Anita D and Caffo, Brian S and Pekar, James J and Mostofsky, Stewart H} } @article {829, title = {Developmental changes in within- and between-network connectivity between late childhood and adulthood.}, journal = {Neuropsychologia}, volume = {51}, year = {2013}, month = {2013 Jan}, pages = {156-67}, abstract = {

A number of behavioral changes occur between late childhood and adulthood, including maturation of social cognition, reward receptivity, impulsiveness, risk-taking and cognitive control. Although some of these abilities show linear improvements with age, some abilities may temporarily worsen, reflecting both the restructuring and/or strengthening of connections within some brain systems. The current study uses resting state functional connectivity to examine developmental differences between late childhood and adulthood in task positive (TP) regions, which play a role in cognitive control functions, and task negative (TN) regions, which play a role in social cognition, self-referential, and internally-directed thought. Within the TP network, developmental differences in connectivity were found with the left dorsolateral prefrontal cortex. Within the TN network, developmental differences in connectivity were found with a broad area of the medial prefrontal cortex and the right parahippocampal gyrus. Connections between the two networks also showed significant developmental differences. Stronger anticorrelations were found in the TN maps of the adult group for the right anterior insula/inferior frontal gyrus, bilateral anterior inferior parietal lobule, bilateral superior parietal lobule and an anterior portion of the right posterior cingulate cortex. There was a significant brain-behavior relationship between the strength of anticorrelation in these regions and inhibitory control performance on two Go/No-go tasks suggesting that the development of anticorrelations between late childhood and adulthood supports mature inhibitory control. Overall, maturation of these networks occurred in specific regions which are associated with cognitive control of goal-directed behavior, including those involved in working memory, social cognition, and inhibitory control.

}, keywords = {Adolescent, Adult, Age Factors, Analysis of Variance, Brain, brain mapping, Child, Child Development, Cognition, Female, Humans, Image Processing, Computer-Assisted, Inhibition (Psychology), Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Neuropsychological Tests, Oxygen, Reaction Time, Young Adult}, issn = {1873-3514}, doi = {10.1016/j.neuropsychologia.2012.11.011}, author = {Barber, Anita D and Caffo, Brian S and Pekar, James J and Mostofsky, Stewart H} } @article {826, title = {Effects of working memory demand on neural mechanisms of motor response selection and control.}, journal = {J Cogn Neurosci}, volume = {25}, year = {2013}, month = {2013 Aug}, pages = {1235-48}, abstract = {

Inhibitory control commonly recruits a number of frontal regions: pre-supplementary motor area (pre-SMA), frontal eye fields (FEFs), and right-lateralized posterior inferior frontal gyrus (IFG), dorsal anterior insula (DAI), dorsolateral prefrontal cortex (DLPFC), and inferior frontal junction (IFJ). These regions may directly implement inhibitory motor control or may be more generally involved in executive control functions. Two go/no-go tasks were used to distinguish regions specifically recruited for inhibition from those that additionally show increased activity with working memory demand. The pre-SMA and IFG were recruited for inhibition in both tasks and did not have greater activation for working memory demand on no-go trials, consistent with a role in inhibitory control. Activation in pre-SMA also responded to response selection demand and was increased with working memory on go trials specifically. The bilateral FEF and right DAI were commonly active for no-go trials. The FEF was also recruited to a greater degree with working memory demand on go trials and may bias top-down information when stimulus-response mappings change. The DAI, additionally responded to increased working memory demand on both go and no-go trials and may be involved in accessing sustained task information, alerting, or autonomic changes when cognitive demands increase. DLPFC activation was consistent with a role in working memory retrieval on both go and no-go trials. The inferior frontal junction, on the other hand, had greater activation with working memory specifically for no-go trials and may detect salient stimuli when the task requires frequent updating of working memory representations.

}, keywords = {Adult, Brain, brain mapping, Choice Behavior, Female, Humans, Image Processing, Computer-Assisted, Inhibition (Psychology), Magnetic Resonance Imaging, Male, Memory, Short-Term, Motor Activity, Neuropsychological Tests, Oxygen, Reaction Time, Young Adult}, issn = {1530-8898}, doi = {10.1162/jocn_a_00394}, author = {Barber, Anita D and Caffo, Brian S and Pekar, James J and Mostofsky, Stewart H} } @article {839, title = {An fMRI-based neurologic signature of physical pain.}, journal = {N Engl J Med}, volume = {368}, year = {2013}, month = {2013 Apr 11}, pages = {1388-97}, abstract = {

BACKGROUND: Persistent pain is measured by means of self-report, the sole reliance on which hampers diagnosis and treatment. Functional magnetic resonance imaging (fMRI) holds promise for identifying objective measures of pain, but brain measures that are sensitive and specific to physical pain have not yet been identified.

METHODS: In four studies involving a total of 114 participants, we developed an fMRI-based measure that predicts pain intensity at the level of the individual person. In study 1, we used machine-learning analyses to identify a pattern of fMRI activity across brain regions--a neurologic signature--that was associated with heat-induced pain. The pattern included the thalamus, the posterior and anterior insulae, the secondary somatosensory cortex, the anterior cingulate cortex, the periaqueductal gray matter, and other regions. In study 2, we tested the sensitivity and specificity of the signature to pain versus warmth in a new sample. In study 3, we assessed specificity relative to social pain, which activates many of the same brain regions as physical pain. In study 4, we assessed the responsiveness of the measure to the analgesic agent remifentanil.

RESULTS: In study 1, the neurologic signature showed sensitivity and specificity of 94\% or more (95\% confidence interval [CI], 89 to 98) in discriminating painful heat from nonpainful warmth, pain anticipation, and pain recall. In study 2, the signature discriminated between painful heat and nonpainful warmth with 93\% sensitivity and specificity (95\% CI, 84 to 100). In study 3, it discriminated between physical pain and social pain with 85\% sensitivity (95\% CI, 76 to 94) and 73\% specificity (95\% CI, 61 to 84) and with 95\% sensitivity and specificity in a forced-choice test of which of two conditions was more painful. In study 4, the strength of the signature response was substantially reduced when remifentanil was administered.

CONCLUSIONS: It is possible to use fMRI to assess pain elicited by noxious heat in healthy persons. Future studies are needed to assess whether the signature predicts clinical pain. (Funded by the National Institute on Drug Abuse and others.).

}, keywords = {Adult, Analgesics, Opioid, Artificial Intelligence, Brain, brain mapping, Female, Hot Temperature, Humans, Magnetic Resonance Imaging, Male, Pain, Pain Measurement, Piperidines, ROC Curve, Sensitivity and Specificity, Young Adult}, issn = {1533-4406}, doi = {10.1056/NEJMoa1204471}, author = {Wager, Tor D and Atlas, Lauren Y and Lindquist, Martin A and Roy, Mathieu and Woo, Choong-Wan and Kross, Ethan} } @article {809, title = {In vivo identification of morphologic retinal abnormalities in neuromyelitis optica.}, journal = {Neurology}, volume = {80}, year = {2013}, month = {2013 Apr 9}, pages = {1406-14}, abstract = {

OBJECTIVE: To assess eyes with neuromyelitis optica (NMO) for morphologic retinal abnormalities utilizing high-definition optical coherence tomography (OCT) imaging.

METHODS: In this cross-sectional study, 39 patients with NMO spectrum disorders and 39 age- and sex-matched healthy controls underwent spectral-domain OCT and visual function testing.

RESULTS: Microcystic macular edema (MME) of the inner nuclear layer (INL) was identified in 10 of 39 patients (26\%) and was exclusively found in eyes with a history of optic neuritis (ON). MME eyes had lower high- and low-contrast letter-acuity scores (100\%: p = 0.002; 2.5\%: p = 0.002; 1.25\%: p = 0.004), lower peripapillary retinal nerve fiber layer (RNFL) thickness (p = 0.04), lower macular RNFL thickness (p = 0.004), lower ganglion cell layer + inner plexiform layer (GCIP) thickness (p = 0.007), higher INL thickness (p < 0.001), and a greater number of ON episodes (p = 0.008) relative to non-MME eyes with a history of ON. After adjusting for history of multiple ON episodes, these findings remained significant for macular-RNFL thickness (p = 0.03), INL thickness (p < 0.001), and 100\% and 2.5\% contrast letter-acuity scores (p = 0.008 and p = 0.03, respectively). NMO spectrum eyes without ON history had lower macular RNFL thickness (p = 0.003), GCIP thickness (p = 0.002), outer nuclear layer thickness (p = 0.02), and low-contrast letter-acuity scores (2.5\%: p = 0.03; 1.25\%: p = 0.002) compared to healthy controls.

CONCLUSIONS: We have identified a pattern of retinal morphologic abnormalities in NMO that is associated with severe retinal axonal and neuronal loss and corresponding visual disability. MME may contribute to poor visual outcomes following NMO-associated ON or alternatively represent a marker of ON severity. Additionally, our results support that subclinical involvement of the anterior visual pathway may occur in NMO spectrum disorders.

}, keywords = {Adolescent, Adult, Aged, Aquaporin 4, Autoantibodies, Case-Control Studies, Chi-Square Distribution, Female, Humans, Macular Edema, Male, Middle Aged, Nerve Fibers, Neuromyelitis Optica, Retina, Tomography, Optical Coherence, Vision Tests, Visual Acuity, Young Adult}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e31828c2f7a}, author = {Sotirchos, Elias S and Saidha, Shiv and Byraiah, Gita and Mealy, Maureen A and Ibrahim, Mohamed A and Sepah, Yasir Jamal and Newsome, Scott D and Ratchford, John N and Frohman, Elliot M and Balcer, Laura J and Crainiceanu, Ciprian M and Nguyen, Quan Dong and Levy, Michael and Calabresi, Peter A} } @article {841, title = {Dissociable influences of opiates and expectations on pain.}, journal = {J Neurosci}, volume = {32}, year = {2012}, month = {2012 Jun 6}, pages = {8053-64}, abstract = {

Placebo treatments and opiate drugs are thought to have common effects on the opioid system and pain-related brain processes. This has created excitement about the potential for expectations to modulate drug effects themselves. If drug effects differ as a function of belief, this would challenge the assumptions underlying the standard clinical trial. We conducted two studies to directly examine the relationship between expectations and opioid analgesia. We administered the opioid agonist remifentanil to human subjects during experimental thermal pain and manipulated participants{\textquoteright} knowledge of drug delivery using an open-hidden design. This allowed us to test drug effects, expectancy (knowledge) effects, and their interactions on pain reports and pain-related responses in the brain. Remifentanil and expectancy both reduced pain, but drug effects on pain reports and fMRI activity did not interact with expectancy. Regions associated with pain processing showed drug-induced modulation during both Open and Hidden conditions, with no differences in drug effects as a function of expectation. Instead, expectancy modulated activity in frontal cortex, with a separable time course from drug effects. These findings reveal that opiates and placebo treatments both influence clinically relevant outcomes and operate without mutual interference.

}, keywords = {Analgesics, Opioid, Anticipation, Psychological, Behavior, brain mapping, Dose-Response Relationship, Drug, Female, Hemodynamics, Hot Temperature, Humans, Image Processing, Computer-Assisted, Injections, Intravenous, Linear Models, Magnetic Resonance Imaging, Male, Pain, Pain Measurement, Piperidines, Young Adult}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.0383-12.2012}, author = {Atlas, Lauren Y and Whittington, Robert A and Lindquist, Martin A and Wielgosz, Joe and Sonty, Nomita and Wager, Tor D} }