Kurt E. Weaver

Association between amygdala response to emotional faces and social anxiety in autism spectrum disorders

Difficulty interpreting facial expressions has been reported in autism spectrum disorders (ASD) and is thought to be associated with amygdala abnormalities. To further explore the neural basis of abnormal emotional face processing in ASD, we conducted an fMRI study of emotional face matching in high-functioning adults with ASD and age, IQ, and gender matched controls. In addition, we investigated whether there was a relationship between self-reported social anxiety and fMRI activation. During fMRI scanning, study participants were instructed to match facial expressions depicting fear or anger. The control condition was a comparable shape-matching task. The control group evidenced significantly increased left prefrontal activation and decreased activation in the occipital lobes compared to the ASD group during emotional face matching. Further, within the ASD group, greater social anxiety was associated with increased activation in right amygdala and left middle temporal gyrus, and decreased activation in the fusiform face area. These results indicate that level of social anxiety mediates the neural response to emotional face perception in ASD.

Mapping anterior temporal lobe language areas with fMRI: A multicenter normative study

Removal of the anterior temporal lobe (ATL) is an effective surgical treatment for intractable temporal lobe epilepsy but carries a risk of language and verbal memory deficits. Preoperative localization of functional zones in the ATL might help reduce these risks, yet fMRI protocols in current widespread use produce very little activation in this region. Based on recent evidence suggesting a role for the ATL in semantic integration, we designed an fMRI protocol comparing comprehension of brief narratives (Story task) with a semantically shallow control task involving serial arithmetic (Math task). The Story > Math contrast elicited strong activation throughout the ATL, lateral temporal lobe, and medial temporal lobe bilaterally in an initial cohort of 18 healthy participants. The task protocol was then implemented at 6 other imaging centers using identical methods. Data from a second cohort of participants scanned at these centers closely replicated the results from the initial cohort. The Story-Math protocol provides a reliable method for activation of surgical regions of interest in the ATL. The bilateral activation supports previous claims that conceptual processing involves both temporal lobes. Used in combination with language lateralization measures, reliable ATL activation maps may be useful for predicting cognitive outcome in ATL surgery, though the validity of this approach needs to be established in a prospective surgical series.

fMRI evidence of neural abnormalities in the subcortical face processing system in ASD

Recent evidence suggests that a rapid, automatic face detection system is supported by subcortical structures including the amygdala, pulvinar, and superior colliculus. Early-emerging abnormalities in these structures may be related to reduced social orienting in children with autism, and subsequently, to aberrant development of cortical circuits involved in face processing. Our objective was to determine whether functional abnormalities in the subcortical face processing system are present in adults with autism spectrum disorders (ASD) during supraliminal fearful face processing. Participants included twenty-eight individuals with ASD and 25 controls group-matched on age, IQ, and behavioral performance. The ASD group met diagnostic criteria on the ADI-R, ADOS-G, and DSM-IV. Both the ASD and control groups showed significant activation in bilateral fusiform gyri. The control group exhibited additional significant responses in the right amygdala, right pulvinar, and bilateral superior colliculi. In the direct group comparison, the controls showed significantly greater activation in the left amygdala, bilateral fusiform gyrus, right pulvinar, and bilateral superior colliculi. No brain region showed significantly greater activation in the ASD group compared to the controls. Thus, basic rapid face identification mechanisms appear to be functional in ASD. However, individuals with ASD failed to engage the subcortical brain regions involved in face detection and automatic emotional face processing, suggesting a core mechanism for impaired socioemotional processing in ASD. Neural abnormalities in this system may contribute to early-emerging deficits in social orienting and attention, the putative precursors to abnormalities in social cognition and cortical face processing specialization.

Direct electrophysiological measurement of human default network areas

Neuroimaging-based investigations in humans have established the existence of brain regions that are selectively metabolically active while resting. We report a population-scale neurophysiological measurement of activity in regions of this “default network,” by recording high-frequency power (76–200 Hz) electrical potentials directly from these regions in three human subjects. A selective increase observed during only resting, when compared with activity, firmly establishes a neuronal origin for default network phenomena.

Longitudinal diffusion tensor imaging in Huntington's Disease.

Serial diffusion tensor imaging scans were collected at baseline and 1 year follow-up to investigate the neurodegenerative profile of white matter (WM) in seven individuals with the Huntingtons Disease (HD) gene mutation and seven control subjects matched on age and gender. In the HD subjects, but not controls, a significant reduction of fractional anisotropy (FA), a measure of WM integrity, between baseline and followup was evident throughout the brain. In addition, a DTI scalar associated with the stability of axons, axial diffusivity, showed significant longitudinal decreases from year 1 to year 2 in HD subjects, declines that overlapped to greater degree with FA discrepancies than longitudinal increases in radial diffusivity, a DTI variable sensitive to demylinization. These preliminary results provide the first longitudinal DTI evidence of WM degeneration in HD and support the notion that FA abnormalities in HD may be a result of axonal injury or withdrawal. These results suggest that longitudinal FA changes may serve as a neuropathological biomarker in HD.

Distributed cortical adaptation during learning of a brain–computer interface task

The majority of subjects who attempt to learn control of a brain–computer interface (BCI) can do so with adequate training. Much like when one learns to type or ride a bicycle, BCI users report transitioning from a deliberate, cognitively focused mindset to near automatic control as training progresses. What are the neural correlates of this process of BCI skill acquisition? Seven subjects were implanted with electrocorticography (ECoG) electrodes and had multiple opportunities to practice a 1D BCI task. As subjects became proficient, strong initial task-related activation was followed by lessening of activation in prefrontal cortex, premotor cortex, and posterior parietal cortex, areas that have previously been implicated in the cognitive phase of motor sequence learning and abstract task learning. These results demonstrate that, although the use of a BCI only requires modulation of a local population of neurons, a distributed network of cortical areas is involved in the acquisition of BCI proficiency.

Local Functional Connectivity as a Pre-Surgical Tool for Seizure Focus Identification in Non-Lesion, Focal Epilepsy

Successful resection of cortical tissue engendering seizure activity is efficacious for the treatment of refractory, focal epilepsy. The pre-operative localization of the seizure focus is therefore critical to yielding positive, post-operative outcomes. In a small proportion of focal epilepsy patients presenting with normal MRI, identification of the seizure focus is significantly more challenging. We examined the capacity of resting state functional MRI (rsfMRI) to identify the seizure focus in a group of four non-lesion, focal (NLF) epilepsy individuals. We predicted that computing patterns of local functional connectivity in and around the epileptogenic zone combined with a specific reference to the corresponding region within the contralateral hemisphere would reliably predict the location of the seizure focus. We first averaged voxel-wise regional homogeneity (ReHo) across regions of interest (ROIs) from a standardized, probabilistic atlas for each NLF subject as well as 16 age- and gender-matched controls. To examine contralateral effects, we computed a ratio of the mean pair-wise correlations of all voxels within a ROI with the corresponding contralateral region (IntraRegional Connectivity – IRC). For each subject, ROIs were ranked (from lowest to highest) on ReHo, IRC, and the mean of the two values. At the group level, we observed a significant decrease in the rank for ROI harboring the seizure focus for the ReHo rankings as well as for the mean rank. At the individual level, the seizure focus ReHo rank was within bottom 10% lowest ranked ROIs for all four NLF epilepsy patients and three out of the four for the IRC rankings. However, when the two ranks were combined (averaging across ReHo and IRC ranks and scalars), the seizure focus ROI was either the lowest or second lowest ranked ROI for three out of the four epilepsy subjects. This suggests that rsfMRI may serve as an adjunct pre-surgical tool, facilitating the identification of the seizure focus in focal epilepsy.

Identifying functional networks using endogenous connectivity in gamma band electrocorticography.

Correlations in spontaneous, infra-slow (<0.1 Hz) fluctuations in gamma band (70-100 Hz) signal recorded using electrocorticography (ECoG) reflect the functional organization of the brain, appearing in auditory and visual sensory cortex, motor cortex, and the default mode network (DMN). We have developed a data-driven method using co-modulation in spontaneous, infra-slow, and gamma band power fluctuations in ECoG to characterize the connectivity between cortical areas. A graph spectral clustering algorithm was used to identify networks that appear consistently. These networks were compared with clinical mapping results obtained using electrocortical stimulation (ECS). We identify networks corresponding to motor and visual cortex with good specificity. Anatomic and functional evidence indicates that other networks, such as the DMN, are also identified by this algorithm. These results indicate that it may be possible to map functional cortex using only spontaneous ECoG recordings. In addition, they support the hypothesis that infra-slow co-modulations of gamma band power represent the neurophysiological basis underlying resting-state networks. Methods examining infra-slow co-modulations in gamma band power will be useful for studying changes in brain connectivity in differing behavioral contexts. Our observations can be made in the absence of observable behavior, suggesting that the electrical mapping of functional cortex is feasible without the use of ECS or task-mediated evoked responses.

Brief report: biochemical correlates of clinical impairment in high functioning autism and Asperger's disorder.

Amygdala dysfunction has been proposed as a critical contributor to social impairment in autism spectrum disorders (ASD). The current study investigated biochemical abnormalities in the amygdala in 20 high functioning adults with autistic disorder or Asperger’s disorder and 19 typically developing adults matched on age and IQ. Magnetic resonance spectroscopy was used to measure N-acetyl aspartate (NAA), creatine/phosphocreatine (Cre), choline/choline containing compounds (Cho), and Myoinositol (mI) in the right and left amygdala. There were no significant between-group differences in any of the metabolites. However, NAA and Cre levels were significantly correlated to clinical ratings on the Autism Diagnostic Interview-Revised. This suggests that altered metabolite levels in the amygdala may be associated with a more severe early developmental course in ASD.

Neurochemical correlates of caudate atrophy in Huntington's disease.

The precise pathogenic mechanisms of Huntingtons disease (HD) are unknown but can be tested in vivo using proton magnetic resonance spectroscopy (1H MRS) to measure neurochemical changes. The objective of this study was to evaluate neurochemical differences in HD gene mutation carriers (HGMCs) versus controls and to investigate relationships among function, brain structure, and neurochemistry in HD. Because previous 1H MRS studies have yielded varied conclusions about HD neurochemical changes, an additional goal was to compare two 1H MRS data analysis approaches. HGMCs with premanifest to early HD and controls underwent evaluation of motor function, magnetic resonance imaging, and localized 1H MRS in the caudate and the frontal lobe. Analytical approaches that were tested included absolute quantitation (unsuppressed water signal as an internal reference) and relative quantification (calculating ratios of all neurochemical signals within a voxel). We identified a suite of neurochemicals that were reduced in concentration proportionally to loss of caudate volume in HGMCs. Caudate concentrations of N‐acetylaspartate (NAA), creatine, choline, and caudate and frontal lobe concentrations of glutamate plus glutamine (Glx) and glutamate were correlated with caudate volume in HGMCs. The relative, but not the absolute, quantitation approach revealed disease‐related differences; the Glx signal was decreased relative to other neurochemicals in the caudate of HGMCs versus controls. This is the first study to demonstrate a correlation among structure, function, and chemical measures in HD brain. Additionally, we demonstrate that a relative quantitation approach may enable the magnification of subtle differences between groups. Observation of decreased Glx suggests that glutamate signaling may be disrupted relatively early in HD, which has important implications for therapeutic approaches.