The human amygdala is a key structure for processing emotional facial expressions, but it remains unclear what aspects of emotion are processed. We investigated this question with three different approaches: behavioural analysis of 3 amygdala lesion patients, neuroimaging of 19 healthy adults, and single-neuron recordings in 9 neurosurgical patients. The lesion patients showed a shift in behavioural sensitivity to fear, and amygdala BOLD responses were modulated by both fear and emotion ambiguity (the uncertainty that a facial expression is categorized as fearful or happy). We found two populations of neurons, one whose response correlated with increasing degree of fear, or happiness, and a second whose response primarily decreased as a linear function of emotion ambiguity. Together, our results indicate that the human amygdala processes both the degree of emotion in facial expressions and the categorical ambiguity of the emotion shown and that these two aspects of amygdala processing can be most clearly distinguished at the level of single neurons.
The human amygdala parametrically encodes the intensity of specific facial emotions and their categorical ambiguity
There is a conflicting literature on facial emotion processing in autism spectrum disorder (ASD): both typical and atypical performance have been reported, and inconsistencies in the literature may stem from different processes examined (emotion judgment, face perception, fixations) as well as differences in participant populations. Here we conducted a detailed investigation of the ability to discriminate graded emotions shown in morphs of fear-happy faces, in a well-characterized high-functioning sample of participants with ASD and matched controls. Signal detection approaches were used in the analyses, and concurrent high-resolution eye-tracking was collected. Although people with ASD had typical thresholds for categorical fear and confidence judgments, their psychometric specificity to detect emotions across the entire range of intensities was reduced. However, fixation patterns onto the stimuli were typical and could not account for the reduced specificity of emotion judgment. Together, our results argue for a subtle and specific deficit in emotion perception in ASD that, from a signal detection perspective, is best understood as a reduced specificity due to increased noise in central processing of the face stimuli.
Keywords: Ambiguity; Autism spectrum disorder; Confidence; Emotion; Eye tracking; Face morph.
Background: Phelan-McDermid syndrome (PMS) occurs as a result of a chromosomal abnormality, most frequently
deletion, in the long arm of chromosome 22, involving the SHANK3 gene. Our goal was to prospectively assess the
neurological phenotype in this syndrome.
METHODS: Twenty-nine participants were recruited from ongoing studies in PMS at the Seaver Autism Center. They
had a structured, uniform neurological examination performed by a pediatric neurologist (Y.F.). Abnormal findings
were graded as mild, moderate or severe. In addition, reports of seizures, magnetic resonance imaging (MRI) and
electroencephalograms (EEG) were reviewed. We calculated the frequency and severity of neurological
abnormalities, as well as correlations between items on the neurological examination and items on the Mullen Scales
of Early Learning and on the Vineland Adaptive Behavioral Scales (VABS).
RESULTS: Hypotonia, abnormal gait, fine motor coordination deficits, and expressive and receptive language delays
were present in all participants. Attention deficits were present in 96% (severe in 62%), and abnormal visual tracking
was present in 86%. A history of seizures was obtained in 44.8% of participants but 46.1% of these were febrile only.
Of the 13 EEG reports available for review – 69.2% were abnormal- with epileptic features present in 53.8%.
Abnormalities were present in 62.5% of MRI reports. Correlations were found between neurological abnormalities
and scores on the Mullen and Vineland Scales.
CONCLUSIONS: Neurological abnormalities are very common in PMS and are correlated with measures of cognitive
and adaptive functioning. The neurological examination may be used for clinical diagnosis, identification of PMS
phenotypes, and, in the future, for evaluation of therapy.
The cognitive phenotype of autism has been correlated with an altered balance of excitation to inhibition in the cerebral cortex, which could result from a change in the number, function, or morphology of GABA-expressing interneurons. The number of GABAergic interneuron subtypes has not been quantified in the autistic cerebral cortex. We classified interneurons into 3 subpopulations based on expression of the calcium-binding proteins parvalbumin, calbindin, or calretinin. We quantified the number of each interneuron subtype in postmortem neocortical tissue from 11 autistic cases and 10 control cases. Prefrontal Brodmann Areas (BA) BA46, BA47, and BA9 in autism and age-matched controls were analyzed by blinded researchers. We show that the number of parvalbumin+ interneurons in these 3 cortical areas-BA46, BA47, and BA9-is significantly reduced in autism compared with controls. The number of calbindin+ and calretinin+ interneurons did not differ in the cortical areas examined. Parvalbumin+ interneurons are fast-spiking cells that synchronize the activity of pyramidal cells through perisomatic and axo-axonic inhibition. The reduced number of parvalbumin+ interneurons could disrupt the balance of excitation/inhibition and alter gamma wave oscillations in the cerebral cortex of autistic subjects. These data will allow development of novel treatments specifically targeting parvalbumin interneurons.
Keywords: autism; basket cells; chandelier cells; interneurons; parvalbumin; prefrontal cortex.
Whole-exome and whole-genome sequencing have facilitated the large-scale discovery of de novo variants in human disease. To date, most de novo discovery through next-generation sequencing focused on congenital heart disease and neurodevelopmental disorders (NDDs). Currently, de novo variants are one of the most significant risk factors for NDDs with a substantial overlap of genes involved in more than one NDD. To facilitate better usage of published data, provide standardization of annotation, and improve accessibility, we created denovo-db (http://denovo-db.gs.washington.edu), a database for human de novo variants. As of July 2016, denovo-db contained 40 different studies and 32,991 de novo variants from 23,098 trios. Database features include basic variant information (chromosome location, change, type); detailed annotation at the transcript and protein levels; severity scores; frequency; validation status; and, most importantly, the phenotype of the individual with the variant. We included a feature on our browsable website to download any query result, including a downloadable file of the full database with additional variant details. denovo-db provides necessary information for researchers to compare their data to other individuals with the same phenotype and also to controls allowing for a better understanding of the biology of de novo variants and their contribution to disease.