Aberrant Striatal Functional Connectivity in Children with Autism

In the paper

“Studies of FC in ASD have found evidence of reduced long-range FC in various cortical circuits (14-24).”

What the sources say

• Supported

  The Discussion reports lower functional connectivity in ASD primarily between frontal and posterior cortices and lists several affected cortical pairs. It cautions that many differences were significant only at an uncorrected threshold and should be considered preliminary; the claim's wording, “found evidence,” is consistent with that caution. (LLM, conf=0.92)

  cites [14] Jones, 2010, Sources of group differences in functional connectivity: An investigation applied to autism spectrum disorder, Neuroimage source
• Not checked yetcites [15] Kennedy, 2006, Failing to deactivate: Resting functional abnormalities in autism, Proc Natl Acad Sci U S A source
• Supported

  The Discussion reports significantly reduced functional connectivity between anterior and posterior medial cortical regions in participants with autism. The Introduction also describes reduced synchronization across brain regions in studies of several cognitive tasks. This paper therefore supports the claim as one of the cited studies finding reduced long-range connectivity. (LLM, conf=0.91)

  cites [16] Cherkassky, 2006, Functional connectivity in a baseline resting-state network in autism, Neuroreport source
• Not checked yetcites [17] Paakki, 2010, Alterations in regional homogeneity of resting-state brain activity in autism spectrum disorders, Brain Res source
• Not checked yetcites [18] Just, 2007, Functional and anatomical cortical underconnectivity in autism: Evidence from an FMRI study of an executive function task and corpus callosum morphometry, Cereb Cortex source
• Supported

  The Functional connectivity section reports lower frontal–parietal connectivity in the autism group than in controls. The Discussion describes this as evidence of impaired long-distance communication between brain regions, supporting this paper’s contribution to the collectively cited claim. (LLM, conf=0.90)

  cites [19] Kana, 2006, Sentence comprehension in autism: Thinking in pictures with decreased functional connectivity, Brain source
• Not checked yetcites [20] Koshino, 2008, fMRI investigation of working memory for faces in autism: Visual coding and underconnectivity with frontal areas, Cereb Cortex source
• Not checked yetcites [21] Castelli, 2002, Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes, Brain source
• Supported

  The Discussion reports significantly reduced functional connectivity between primary visual cortex (area 17) and inferior frontal cortex (areas 44 and 45) in the autism group compared with controls. This study therefore provides an example of the reduced long-range connectivity described in the multi-citation sentence; it does not need to establish reductions in every circuit. (LLM, conf=0.92)

  cites [22] Villalobos, 2005, Reduced functional connectivity between V1 and inferior frontal cortex associated with visuomotor performance in autism, Neuroimage source
• Not checked yetcites [23] Welchew, 2005, Functional disconnectivity of the medial temporal lobe in Asperger's syndrome, Biol Psychiatry source

In the paper

“Consistent with a role of pSTG in these processes, fMRI studies of ASD have demonstrated abnormal activation of the pSTG during tasks involving perception of intentional movements, particularly in the right hemisphere (86-88).”

What the sources say

• Partly supported

  The Results report reduced right superior temporal gyrus activity in children with ASD during perception of potentially ironic scenarios, supporting the abnormal-activation finding. The task involved interpreting facial expression and tone of voice, not perceiving intentional movements; the cited passages also do not establish that the affected region was specifically posterior STG. Page numbers were not available in our copy. (LLM, conf=0.83)

  cites [86] Wang, 2007, Reading affect in the face and voice: Neural correlates of interpreting communicative intent in children and adolescents with autism spectrum disorders, Arch Gen Psychiatry sourceExperimental — accuracy not yet measured
• Not checked yetcites [87] von dem Hagen, 2010, Autism spectrum traits in the typical population predict structure and function in the posterior superior temporal sulcus [published online ahead of print May 3], Cereb Cortex
• Not checked yetcites [88] Toal, 2010, Clinical and anatomical heterogeneity in autistic spectrum disorder: A structural MRI study, Psychol Med source

In the paper

“while the left VSi showed positive FC with the left supramarginal gyrus in TDC, these two regions were negatively connected in the ASD group”

In the paper

“For nearly all of the aberrant circuits, significantly positive FC was observed in the ASD group, but FC was either absent or negative in each of the other two groups (TDC, TA).”

In the paper

“Patterns of striatal FC obtained for TDC were grossly similar to those previously obtained with TA (42;44;45) though with notably more diffuse and stronger local positive FC”

What the sources say

• Not checked yetcites [42] Postuma, 2006, Basal ganglia functional connectivity based on a meta-analysis of 126 positron emission tomography and functional magnetic resonance imaging publications, Cereb Cortex source
• Not checked yetcites [44] Kelly, 2009, L-dopa modulates functional connectivity in striatal cognitive and motor networks: A double-blind placebo-controlled study, J Neurosci source
• Not checked yetcites [45] Hazlett, 2005, Magnetic resonance imaging and head circumference study of brain size in autism: Birth through age 2 years, Arch Gen Psychiatry source

In the paper

“However, in the ASD group, nearly all striatal seeds showed significantly stronger and more diffuse FC with both regions typically included in striatal networks, as well as with ectopic areas, which are not functionally connected with the striatum in TDC.”

In the paper

“Both child groups also showed positive FC with anterior and posterior insula, as well as with superior and middle temporal gyri bilaterally, areas not typically observed in DC circuitry in TA.”

In the paper

“Research-reliable scores were obtained for 17 (85%) children using the new diagnostic ADOS algorithm (53).”

What the sources say

• Not checked yetcites [53] Kaufman, 1997, Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime version (K-SADS-PL): Initial reliability and validity data, J Am Acad Child Adolesc Psychiatry source

In the paper

“We employed six previously validated (42) striatal regions of interest (“seeds”).”

What the sources say

• Not checked yetcites [42] Postuma, 2006, Basal ganglia functional connectivity based on a meta-analysis of 126 positron emission tomography and functional magnetic resonance imaging publications, Cereb Cortex source

In the paper

“caudate hyperactivation was evident in a study of sensorimotor processes in ASD (41).”

What the sources say

• Not checked yetcites [41] Di Martino, 2008, Functional connectivity of human striatum: A resting state FMRI study, Cereb Cortex source

In the paper

“Consistent with our primary analyses we computed partial correlations, controlling for age and IQ.”

In the paper

“in a task-based fMRI study, increased striatal FC with frontal, parietal, and occipital lobes was reported in adults with ASD during a sensorimotor task, relative to TA (35).”

What the sources say

• Not checked yetcites [35] Qiu, 2010, Basal ganglia shapes predict social, communication, and motor dysfunctions in boys with autism spectrum disorder, J Am Acad Child Adolesc Psychiatry

In the paper

“FC analyses in data registered to a local template yielded substantially similar results (Figure S3 in Supplement 1).”

In the paper

“Gaussian Random Field theory was used for cluster-level multiple comparisons correction (min Z > 2.3; p < 0.05, corrected).”

In the paper

“We enrolled 26 children with ASD and excluded six children due to excessive movement.”

In the paper

“Caucasian (11 and 8, in the TDC and ASD groups, respectively) and African American (4 and 3 for the TDC and the ASD groups, respectively) predominated (groups did not differ).”

In the paper

“18 of the 20 children with ASD were right-handed (groups did not differ).”

In the paper

“We did not covary sex given the few females (3 ASD, 6 TDC).”

In the paper

“Models of ASD as a brain dysconnection syndrome (8-13) have emerged from analyses of abnormalities in cortico-cortical connections.”

What the sources say

• Not checked yetcites [8] Frith, 2004, Is autism a disconnection disorder?, Lancet Neurol source
• Not checked yetcites [9] Belmonte, 2004, Autism as a disorder of neural information processing: Directions for research and targets for therapy, Mol Psychiatry source
• Not checked yetcites [10] Just, 2004, Cortical activation and synchronization during sentence comprehension in high-functioning autism: Evidence of underconnectivity, Brain source
• Not checked yetcites [11] Minshew, 2007, The new neurobiology of autism: Cortex, connectivity, and neuronal organization, Arch Neurol source
• Not checked yetcites [12] Geschwind, 2007, Autism spectrum disorders: Developmental disconnection syndromes, Curr Opin Neurobiol source
• Not checked yetcites [13] Hughes, 2007, Autism: The first firm finding = underconnectivity?, Epilepsy Behav source

In the paper

“Concurrently, the strength of FC between cortical and subcortical regions progressively decreases (6), suggesting decreased subcortical influence over cortical functioning with age.”

What the sources say

• Not checked yetcites [6] Supekar, 2009, Development of large-scale functional brain networks in children, PLoS Biol source

In the paper

“diffuse patterns of local FC are gradually replaced by a distributed architecture, dominated by focal long-range connections (3-6).”

What the sources say

• Not checked yetcites [3] Fair, 2007, Development of distinct control networks through segregation and integration, Proc Natl Acad Sci U S A source
• Not checked yetcites [4] Fair, 2008, The maturing architecture of the brain's default network, Proc Natl Acad Sci U S A source
• Not checked yetcites [5] Kelly, 2009, Development of anterior cingulate functional connectivity from late childhood to early adulthood, Cereb Cortex source
• Not checked yetcites [6] Supekar, 2009, Development of large-scale functional brain networks in children, PLoS Biol source

In the paper

“Morphological studies have generally reported increased caudate volume in ASD (37;38).”

What the sources say

• Not checked yetcites [37] Stanfield, 2008, Towards a neuroanatomy of autism: A systematic review and meta-analysis of structural magnetic resonance imaging studies, Eur Psychiatry source
• Not checked yetcites [38] Dapretto, 2006, Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders, Nat Neurosci source

In the paper

“Overall, this literature suggests abnormal striatal-cortical circuits in ASD and highlights the need for their direct investigation in this population.”

In the paper

“Secondary analyses comparing TDC to TA, were conducted covarying age and sex.”

In the paper

“However, given their wide ranges (Table 1), we covaried age and full-scale IQ.”

In the paper

“The ASD and the TDC groups did not differ significantly with respect to IQ, age, sex, or SES.”

In the paper

“Disturbances in these maturational processes are increasingly implicated in neurodevelopmental conditions such as autism spectrum disorders (ASD) (7).”

What the sources say

• Not checked yetcites [7] Courchesne, 2007, Mapping early brain development in autism, Neuron source

In the paper

“These are ventral and dorsal AI areas, associated with empathy and cognitive functions respectively, a posterior region associated with sensorimotor processes, and an intermediate region involved in olfactory-gustatory functions (76).”

What the sources say

• Not checked yetcites [76] Silani, 2008, Levels of emotional awareness and autism: An fMRI study, Soc Neurosci source

In the paper

“Although our sample size is on-par with functional imaging studies of ASD, larger samples are needed to account for the marked heterogeneity characteristic of ASD.”

In the paper

“For example, initial R-fMRI work has revealed ASD-related increases in FC between STG and PCC (28) and increased regional homogeneity of temporal cortices including STG (92).”

What the sources say

• Not checked yetcites [28] Monk, 2009, Abnormalities of intrinsic functional connectivity in autism spectrum disorders, Neuroimage source

In the paper

“a recent meta-analysis of functional imaging studies of autism highlighted ASD-related insula hypoactivation in studies examining social processing (30)”

What the sources say

• Not checked yetcites [30] Di Martino, 2009, Relationship between cingulo-insular functional connectivity and autistic traits in neurotypical adults, Am J Psychiatry source

In the paper

“For example, initial R-fMRI work has revealed ASD-related increases in FC between STG and PCC (28) and increased regional homogeneity of temporal cortices including STG (92).”

What the sources say

• Not checked yetcites [92] Fernandez-Gil, 2010, Anatomy of the brainstem: A gaze into the stem of life, Semin Ultrasound CT MRI source

In the paper

“Posterior divisions of the right STG (pSTG) have been implicated in perception of intentional movements such as eye gaze (81), salience of acoustic cues (82;83), prediction of reward based on other agents’ strategies (84), and live face-to-face interactions (85).”

What the sources say

• Not checked yetcites [81] Redcay, 2008, The superior temporal sulcus performs a common function for social and speech perception: Implications for the emergence of autism, Neurosci Biobehav Rev source
• Not checked yetcites [82] Haruno, 2009, Activity in the superior temporal sulcus highlights learning competence in an interaction game, J Neurosci source
• Not checked yetcites [83] Redcay, 2010, Live face-to-face interaction during fMRI: A new tool for social cognitive neuroscience, Neuroimage source
• Not checked yetcites [84] Frith, 2001, Mind blindness and the brain in autism, Neuron source

In the paper

“Finally, even though cortico-striatal circuits are mediated by the thalamus, we did not examine the thalamus directly because of current limitations on thalamic functional parcellation.”

In the paper

“Additionally, we included too few females to examine group by sex interactions.”

In the paper

“Evidence from neuropathology (96) and electrophysiology (97) also implicate the brainstem in ASD; morphometric studies of individuals with ASD have revealed reduced grey and white matter in the pons, and brainstem more broadly (90;e.g., 98).”

What the sources say

• Not checked yetcites [90] Shukla, 2010, Regional homogeneity of fMRI time series in autism spectrum disorders, Neurosci Lett source
• Not checked yetcites [98] Zhang, 2008, Intrinsic functional relations between human cerebral cortex and thalamus, J Neurophysiol source

In the paper

“Along with sample size, failure to detect robust relationships between FC and symptom severity may reflect our failure to sample symptoms beyond the cardinal diagnostic domains.”

In the paper

“ASD-related abnormalities in temporal gyri gray matter have also been noted (90).”

What the sources say

• Not checked yetcites [90] Shukla, 2010, Regional homogeneity of fMRI time series in autism spectrum disorders, Neurosci Lett source

In the paper

“Increased FC between STG and frontal cortex in ASD emerged from a study of language processes (91), while R-fMRI studies of ASD are beginning to reveal STG abnormalities.”

What the sources say

• Not checked yetcites [91] Dawson, 2005, Neurocognitive and electrophysiological evidence of altered face processing in parents of children with autism: Implications for a model of abnormal development of social brain circuitry in autism, Dev Psychopathol source

In the paper

“This resembles TDC functional architecture rather than that of TA (3;5;25), suggesting developmental immaturity in ASD.”

What the sources say

• Not checked yetcites [3] Fair, 2007, Development of distinct control networks through segregation and integration, Proc Natl Acad Sci U S A source
• Not checked yetcites [5] Kelly, 2009, Development of anterior cingulate functional connectivity from late childhood to early adulthood, Cereb Cortex source
• Not checked yetcites [25] Uddin, 2010, Typical and atypical development of functional human brain networks: insights from resting-state FMRI, Front Syst Neurosci source

In the paper

“increased local and reduced long-range FC- characteristic of immature development- has been reported to be widespread in Tourette’s disorder (along with two anomalous circuits) (67) and was also found in ADHD (68).”

What the sources say

• Not checked yetcites [67] Castellanos, 2008, Cingulate-precuneus interactions: A new locus of dysfunction in adult attention-deficit/hyperactivity disorder, Biol Psychiatry source
• Not checked yetcites [68] Mizuno, 2006, Partially enhanced thalamocortical functional connectivity in autism, Brain Res source

In the paper

“Our results support broadening the focus of examination in ASD to regions involved in early stages of brain development, such as the brainstem, insula, and striatum.”

In the paper

“In that study, the severity of autistic traits was directly related to the extent to which FC between mid-insula and pregenual ACC resembled that of the ventral AI (low autistic traits) as opposed to posterior insular regions (high autistic traits; 30).”

What the sources say

• Not checked yetcites [30] Di Martino, 2009, Relationship between cingulo-insular functional connectivity and autistic traits in neurotypical adults, Am J Psychiatry source

In the paper

“Recent work showed that reductions in white matter volume and hypoactivation of the pSTG during a Stroop task positively correlated with levels of autistic traits in TA (89).”

What the sources say

• Not checked yetcites [89] Shih, 2010, Atypical network connectivity for imitation in autism spectrum disorder, Neuropsychologia source

In the paper

“Functional hyperconnectivity in clinical populations is increasingly interpreted as reflecting delayed or stunted maturational processes.”

What the sources say

• Not checked yetcites [67] Castellanos, 2008, Cingulate-precuneus interactions: A new locus of dysfunction in adult attention-deficit/hyperactivity disorder, Biol Psychiatry source
• Not checked yetcites [68] Mizuno, 2006, Partially enhanced thalamocortical functional connectivity in autism, Brain Res source

In the paper

“Noting the early ontogeny of brainstem development and evidence of increased prevalence of putative ASD cases associated with early exposure to teratogens affecting brainstem development (95), models of autism have posited brainstem abnormalities (66).”

What the sources say

• Not checked yetcites [95] Russo, 2008, Deficient brainstem encoding of pitch in children with autism spectrum disorders, Clin Neurophysiol source
• Not checked yetcites [66] Church, 2009, Control networks in paediatric Tourette syndrome show immature and anomalous patterns of functional connectivity, Brain source

In the paper

“recent work suggests that AI function may be more directly related to alexithymia, a phenomenon that is associated with, but distinct from, impaired empathy (77;78).”

What the sources say

• Not checked yetcites [77] Craig, 2003, Interoception: The sense of the physiological condition of the body, Curr Opin Neurobiol source
• Not checked yetcites [78] 2000

In the paper

“the anterior insula (AI) which is implicated in empathy (72), task-control (73), and more broadly, in the ability to integrate visceral, autonomic processes to guide behavior (74-76).”

What the sources say

• Not checked yetcites [72] Craig, 2009, How do you feel—now?, Nat Rev Neurosci source
• Not checked yetcites [73] Seeley, 2007, Dissociable intrinsic connectivity networks for salience processing and executive control, J Neurosci source
• Not checked yetcites [74] Kurth, 2010, A link between the systems: Functional differentiation and integration within the human insula revealed by meta-analysis, Brain Struct Funct source
• Not checked yetcites [75] Bird, 2010, Empathic brain responses in insula are modulated by levels of alexithymia but not autism, Brain source
• Not checked yetcites [76] Silani, 2008, Levels of emotional awareness and autism: An fMRI study, Soc Neurosci source

In the paper

“A meta-analysis of 1768 task-based functional imaging studies highlighted the heterogeneity of insular cortex and identified four functionally distinct areas (76).”

What the sources say

• Not checked yetcites [76] Silani, 2008, Levels of emotional awareness and autism: An fMRI study, Soc Neurosci source

In the paper

“Incomplete coverage of the cerebellum in some participants prevented full analyses of striatal-cerebellar functional interactions.”