Hyperacusis in Tinnitus Individuals Is Associated with Smaller Gray Matter Volumes in the Supplementary Motor Area Regardless of Hearing Levels.

Recent evidence suggests a connection between hyperacusis and the motor system of the brain. For instance, our recent study reported that hyperacusis in participants with tinnitus and hearing loss is associated with smaller gray matter volumes in the supplementary motor area (SMA). Given that hearing loss can affect gray matter changes in tinnitus, this study aimed to determine if the changes reported in our previous findings of smaller SMA gray matter volumes in hyperacusis persist in the absence of hearing loss. Data for this study were gathered from four prior studies conducted between 2004 and 2019 at the University Medical Centre Groningen (UMCG). A total of 101 participants with tinnitus and either clinically normal hearing (normal hearing with tinnitus or NHT, n = 35) or bilateral sensorineural hearing loss (hearing loss with tinnitus or HLT, n = 66) were included across four studies. Hyperacusis was determined by a score of ≥22 on the Hyperacusis Questionnaire (HQ). In the NHT group, 22 (63%) participants scored ≥22 on the HQ (NHT with hyperacusis: mean age 44.1 years, 12 females), while in the HLT group, 25 (38%) participants scored ≥22 on the HQ (HLT with hyperacusis: mean age 59.5 years, 10 females). The 2 × 2 between-group ANOVAs revealed that hyperacusis is associated with smaller SMA gray matter volumes, regardless of hearing levels. Notably, the smaller SMA gray matter volumes in hyperacusis were primarily influenced by the attentional subscales of the HQ. The association between hyperacusis and the motor system may indicate a constant alertness to sounds and a readiness for motor action.

Sound-Evoked Neural Activity in Normal-Hearing Tinnitus: Effects of Frequency and Stimulated Ear Side.

Tinnitus is a common phantom auditory percept believed to be related to plastic changes in the brain due to hearing loss. However, tinnitus can also occur in the absence of any clinical hearing loss. In this case, since there is no hearing loss, the mechanisms that drive plastic changes remain largely enigmatic. Previous studies showed subtle differences in sound-evoked brain activity associated with tinnitus in subjects with tinnitus and otherwise normal hearing, but the results are not consistent across studies. Here, we aimed to investigate these differences using monaural rather than binaural stimuli. Sound-evoked responses were measured using functional magnetic resonance imaging (MRI) in participants with and without tinnitus. All participants had clinically normal audiograms. The stimuli were pure tones with frequencies between 353 and 8000 Hz, presented monaurally. A Principal Component Analysis (PCA) of the response in the auditory cortex revealed no difference in tonotopic organization, which confirmed earlier studies. A GLM analysis showed hyperactivity in the lateral areas of the bilateral auditory cortex. Consistent with the tonotopic map, this hyperactivity mainly occurred in response to low stimulus frequencies. This may be related to hyperacusis. Furthermore, there was an interaction between stimulation side and tinnitus in the parahippocampus. This may reflect an interference between tinnitus and spatial orientation.

Hyperacusis is associated with smaller gray matter volumes in the supplementary motor area.

Hyperacusis is a disorder in loudness perception characterized by increased sensitivity to ordinary environmental sounds and associated with otologic conditions, including hearing loss and tinnitus (the phantom perception of sound) as well as neurologic and neuropsychiatric conditions. Hyperacusis is believed to arise centrally in the brain; however, the underlying causes are unknown. To gain insight into differences in brain morphology associated with hyperacusis, we undertook a retrospective case-control study comparing whole-brain gray matter morphology in participants with sensorineural hearing loss and tinnitus who either scored above or below the threshold for hyperacusis based on a standard questionnaire. We found that participants reporting hyperacusis had smaller gray matter volumes and cortical sheet thicknesses in the right supplementary motor area (SMA), independent of anxiety, depression, tinnitus burden, or sex. In fact, the right SMA volumes extracted from an independently defined volume of interest could accurately classify participants. Finally, in a subset of participants where functional data were also available, we found that individuals with hyperacusis showed increased sound-evoked responses in the right SMA compared to individuals without hyperacusis. Given the role of the SMA in initiating motion, these results suggest that in hyperacusis the SMA is involved in a motor response to sounds.

A Combined Image- and Coordinate-Based Meta-Analysis of Whole-Brain Voxel-Based Morphometry Studies Investigating Subjective Tinnitus.

Previous voxel-based morphometry (VBM) studies investigating tinnitus have reported structural differences in a variety of spatially distinct gray matter regions. However, the results have been highly inconsistent and sometimes contradictory. In the current study, we conducted a combined image- and coordinate-based meta-analysis of VBM studies investigating tinnitus to identify robust gray matter differences associated with tinnitus, as well as examine the possible effects of hearing loss on the outcome of the meta-analysis. The PubMed and Web of Science databases were searched for studies published up to August 2021. Additional manual searches were conducted for studies published up to December 2021. A whole-brain meta-analysis was performed using Seed-Based d Mapping with Permutation of Subject Images (SDM-PSI). Fifteen studies comprising 423 individuals with tinnitus and either normal hearing or hearing loss (mean age 50.94 years; 173 females) and 508 individuals without tinnitus and either normal hearing or hearing loss (mean age 51.59 years; 234 females) met the inclusion criteria. We found a small but significant reduction in gray matter in the left inferior temporal gyrus for groups of normal hearing individuals with tinnitus compared to groups of hearing-matched individuals without tinnitus. In sharp contrast, in groups with hearing loss, tinnitus was associated with increased gray matter levels in the bilateral lingual gyrus and the bilateral precuneus. Those results were dependent upon matching the hearing levels between the groups with or without tinnitus. The current investigation suggests that hearing loss is the driving force of changes in cortical gray matter across individuals with and without tinnitus. Future studies should carefully account for confounders, including hearing loss, hyperacusis, anxiety, and depression, to identify gray matter changes specifically related to tinnitus. Ultimately, the aggregation of standardized individual datasets with both anatomical and useful phenotypical information will permit a better understanding of tinnitus-related gray matter differences, the effects of potential comorbidities, and their interactions with tinnitus.

Increased Functional Connectivity Between Subcortical and Cortical Resting-State Networks in Autism Spectrum Disorder.

IMPORTANCE: Individuals with autism spectrum disorder (ASD) exhibit severe difficulties in social interaction, motor coordination, behavioral flexibility, and atypical sensory processing, with considerable interindividual variability. This heterogeneous set of symptoms recently led to investigating the presence of abnormalities in the interaction across large-scale brain networks. To date, studies have focused either on constrained sets of brain regions or whole-brain analysis, rather than focusing on the interaction between brain networks. OBJECTIVES: To compare the intrinsic functional connectivity between brain networks in a large sample of individuals with ASD and typically developing control subjects and to estimate to what extent group differences would predict autistic traits and reflect different developmental trajectories. DESIGN, SETTING, AND PARTICIPANTS: We studied 166 male individuals (mean age, 17.6 years; age range, 7-50 years) diagnosed as having DSM-IV-TR autism or Asperger syndrome and 193 typical developing male individuals (mean age, 16.9 years; age range, 6.5-39.4 years) using resting-state functional magnetic resonance imaging (MRI). Participants were matched for age, IQ, head motion, and eye status (open or closed) in the MRI scanner. We analyzed data from the Autism Brain Imaging Data Exchange (ABIDE), an aggregated MRI data set from 17 centers, made public in August 2012. MAIN OUTCOMES AND MEASURES: We estimated correlations between time courses of brain networks extracted using a data-driven method (independent component analysis). Subsequently, we associated estimates of interaction strength between networks with age and autistic traits indexed by the Social Responsiveness Scale. RESULTS: Relative to typically developing control participants, individuals with ASD showed increased functional connectivity between primary sensory networks and subcortical networks (thalamus and basal ganglia) (all t ≥ 3.13, P < .001 corrected). The strength of such connections was associated with the severity of autistic traits in the ASD group (all r ≥ 0.21, P < .0067 corrected). In addition, subcortico-cortical interaction decreased with age in the entire sample (all r ≤ -0.09, P < .012 corrected), although this association was significant only in typically developing participants (all r ≤ -0.13, P < .009 corrected). CONCLUSIONS AND RELEVANCE: Our results showing ASD-related impairment in the interaction between primary sensory cortices and subcortical regions suggest that the sensory processes they subserve abnormally influence brain information processing in individuals with ASD. This might contribute to the occurrence of hyposensitivity or hypersensitivity and of difficulties in top-down regulation of behavior.

Object visibility alters the relative contribution of ventral visual stream and mirror neuron system to goal anticipation during action observation.

We used fMRI to study the effect of hiding the target of a grasping action on the cerebral activity of an observer whose task was to anticipate the size of the object being grasped. Activity in the putative mirror neuron system (pMNS) was higher when the target was concealed from the view of the observer and anticipating the size of the object being grasped requested paying attention to the hand kinematics. In contrast, activity in ventral visual areas outside the pMNS increased when the target was fully visible, and the performance improved in this condition. A repetition suppression analysis demonstrated that in full view, the size of the object being grasped by the actor was encoded in the ventral visual stream. Dynamic causal modeling showed that monitoring a grasping action increased the coupling between the parietal and ventral premotor nodes of the pMNS. The modulation of the functional connectivity between these nodes was correlated with the subject's capability to detect the size of hidden objects. In full view, synaptic activity increased within the ventral visual stream, and the connectivity with the pMNS was diminished. The re-enactment of observed actions in the pMNS is crucial when interpreting others' actions requires paying attention to the body kinematics. However, when the context permits, visual-spatial information processing may complement pMNS computations for improved action anticipation accuracy.

Age-related increase in inferior frontal gyrus activity and social functioning in autism spectrum disorder.

BACKGROUND: Hypoactivation of the inferior frontal gyrus during the perception of facial expressions has been interpreted as evidence for a deficit of the mirror neuron system in children with autism. We examined whether this dysfunction persists in adulthood, and how brain activity in the mirror neuron system relates to social functioning outside the laboratory. METHODS: Twenty-one adult males with autism spectrum disorders and 21 typically developing subjects matched for age, sex, and IQ were scanned in three conditions: observing short movies showing facial expressions, performing a facial movement, and experiencing a disgusting taste. Symptom severity and level of social adjustment were measured with the Autism Diagnostic Observation Schedule and the Social Functioning Scale. RESULTS: Inferior frontal gyrus activity during the observation of facial expressions increased with age in subjects with autism, but not in control subjects. The age-related increase in activity was associated with changes in gaze behavior and improvements in social functioning. These age-related neurocognitive improvements were not found in a group of individuals with schizophrenia, who had comparable levels of social functioning. CONCLUSIONS: The results of this cross-sectional study suggest that mirror neuron system activity augments with age in autism and that this is accompanied by changes in gaze behavior and improved social functioning. It is the first demonstration of an age-related neurocognitive improvement in autism. Increased motor simulation may contribute to the amelioration in social functioning documented in adolescence and adulthood. This finding should encourage the development of new therapeutic interventions directed at emotion simulation.

Empathy: shared circuits and their dysfunctions.

Observing another individual acting upon an object triggers cerebral activity well beyond the visual cortex of the observer in areas directly involved in planning and executing actions. This we will call action simulation. Importantly, the brain does not solely simulate the actions of others but also the sensations they feel, and their emotional responses. These simulation mechanisms are most active in individuals who report being very empathic. Simulation may indeed be instrumental for our understanding of the emotional and mental state of people in our sight, and may contribute heavily to the social interactions with our peers by providing a first-person perspective on their inner feelings. Simulation mechanisms are at work at an early stage of social development and might be defective in young individuals with autism spectrum disorders (ASD). However, the results to date regarding ASD are not clearcut, and an equal number of studies report positive and negative findings.

Action understanding: how, what and why.

The mirror neuron system may help us understand how others act and what they do. A recent study has shown that consciously reflecting on their intentions additionally recruits mentalizing areas.

The day of the week when you were born in 700 ms: calendar computation in an Autistic savant.

Some individuals are able to determine the weekday of a given date in a few seconds (finding for instance that June 12, 1900, was a Tuesday). This ability has fascinated scientists for many years because it is predominantly observed in people with limited intelligence and may appear very early in life. Exceptional visual memory, exceptional concentration abilities, or privileged access to lower levels of information not normally available through introspection have been advanced to explain such phenomena. In the present article, the authors show that a simple cognitive model can explain all aspects of the performance of Donny, a young autistic savant who is possibly the fastest and most accurate calendar prodigy ever described.

Task-independent semantic activation for numbers and animals.

UNLABELLED: Semantic processing of numbers and animals was contrasted with PET in two different tasks (comparison and classification) to test the hypothesis that knowledge about numbers is associated with increased activation in the parietal cortices, regardless of the semantic task (i.e. CLASSIFICATION: is seven odd? Comparison: is seven larger than 5?). By contrast, processing animal names was expected to produce activation in inferior temporal areas. Task-independent activation was observed in the left and right intraparietal sulci for number names, whereas task-independent activation of the left inferior temporal gyrus was found for animal names. No significant interaction between the category (numbers or animals) and the semantic task (comparison or classification) was observed. Accordingly, the IPS activation classically observed during numerical processing appears to be related to category-specific semantic knowledge about numbers. Likewise, the activation of the inferior temporal gyrus associated with the processing of animal names is probably related to category-specific knowledge about animals. The results strongly support the hypothesis that different brain regions are important for storing conceptual knowledge about different semantic categories.