Brain responses in aggression-prone individuals: A systematic review and meta-analysis of functional magnetic resonance imaging (fMRI) studies of anger- and aggression-eliciting tasks

Background: While reactive aggression (in response to a perceived threat or provocation) is part of humans' adaptive behavioral repertoire, it can violate social and legal norms. Understanding brain function in individuals with high levels of reactive aggression as they process anger- and aggression-eliciting stimuli is critical for refining interventions. Three neurobiological models of reactive aggression - the limbic hyperactivity, prefrontal hypoactivity, and dysregulated limbic-prefrontal connectivity models - have been proposed. However, these models are based on neuroimaging studies involving mainly healthy individuals, leaving it unclear which model best describes brain function in aggression-prone individuals. Methods: We conducted a systematic literature search (PubMed and Psycinfo) and Multilevel Kernel Density meta-analysis (MKDA) of nine functional magnetic resonance imaging (fMRI) studies of brain responses to tasks putatively eliciting anger and aggression in aggression-prone individuals alone, and relative to healthy controls. Results: Aggression-prone individuals exhibited greater activity during reactive aggression relative to baseline in the superior temporal gyrus and in regions comprising the cognitive control and default mode networks (right posterior cingulate cortex, precentral gyrus, precuneus, right inferior frontal gyrus). Compared to healthy controls, aggression-prone individuals exhibited increased activity in limbic regions (left hippocampus, left amygdala, left parahippocampal gyrus) and temporal regions (superior, middle, inferior temporal gyrus), and reduced activity in occipital regions (left occipital cortex, left calcarine cortex). Conclusions: These findings lend support to the limbic hyperactivity model and further indicate altered temporal and occipital activity in anger- and aggression-eliciting situations that involve face and speech processing.

Atypically slow processing of faces and non-faces in older autistic adults

Face recognition is a fundamental function that requires holistic processing. Differences in face processing have been consistently identified in autistic children, but it is unknown whether these differences persist across the adult lifespan. Using event-related functional magnetic resonance imaging, we measured holistic face processing with a rapid Mooney faces task in 50 autistic and 49 non-autistic participants (30–74 years). Behavioral tasks included a self-paced version of the same paradigm and a global–local processing task (Navon). Reduced detection rates for faces, but not non-faces, were found in autistic adults, including slower responses on all conditions. Without time constraints, differences in accuracy disappeared between groups, although reaction times in correctly identifying faces remained higher in autistic adults. The functional magnetic resonance imaging results showed lower activation in the left and right superior frontal gyrus in the autism group but no age-related differences. Overall, our findings point toward slower information processing speed rather than a face recognition deficit in autistic adults. This suggests that face-processing differences are not a core feature of autism across the adult lifespan. Lay abstract Some theories suggested that social difficulties in autism arise from differences in the processing of faces. If face-processing difficulties are central to autism, then they should be as persistent as social difficulties across the lifespan. We tested this by asking autistic and neurotypical participants between 30 and 75 years to complete face detection tasks. Both autistic and neurotypical adults responded more slowly with age. When participants had to respond quickly, autistic adults made more errors in face detection regardless of their age. However, when the time constraint was removed, autistic adults performed as well as the neurotypical group. Across tasks, autistic adults responded more slowly when asked to detect both face and non-face stimuli. We also investigated brain activation differences in the face detection task with functional magnetic resonance imaging. The results indicated lower activation in the autism group in the left and right superior frontal gyrus. The superior frontal gyrus is not typically implicated in face processing but in more general processing, for example, keeping instructions in mind and following them. Together with the behavioral results, this suggests that there is no specific deficit in face processing in autistic adults between 30 and 75 years. Instead, the results suggest differences in general processing, particularly in the speed of processing. However, this needs to be investigated further with methods that are more sensitive to the timing of brain activation.

Gradual Restraint Habituation for Awake Functional Magnetic Resonance Imaging Combined With a Sparse Imaging Paradigm Reduces Motion Artifacts and Stress Levels in Rodents

Functional magnetic resonance imaging, as a non-invasive technique, offers unique opportunities to assess brain function and connectivity under a broad range of applications, ranging from passive sensory stimulation to high-level cognitive abilities, in awake animals. This approach is confounded, however, by the fact that physical restraint and loud unpredictable acoustic noise must inevitably accompany fMRI recordings. These factors induce marked stress in rodents, and stress-related elevations of corticosterone levels are known to alter information processing and cognition in the rodent. Here, we propose a habituation strategy that spans specific stages of adaptation to restraint, MRI noise, and confinement stress in awake rats and circumvents the need for surgical head restraint. This habituation protocol results in stress levels during awake fMRI that do not differ from pre-handling levels and enables stable image acquisition with very low motion artifacts. For this, rats were gradually trained over a period of three weeks and eighteen training sessions. Stress levels were assessed by analysis of fecal corticosterone metabolite levels and breathing rates. We observed significant drops in stress levels to below pre-handling levels at the end of the habituation procedure. During fMRI in awake rats, after the conclusion of habituation and using a non-invasive head-fixation device, breathing was stable and head motion artifacts were minimal. A task-based fMRI experiment, using acoustic stimulation, conducted 2 days after the end of habituation, resulted in precise whole brain mapping of BOLD signals in the brain, with clear delineation of the expected auditory-related structures. The active discrimination by the animals of the acoustic stimuli from the backdrop of scanner noise was corroborated by significant increases in BOLD signals in the thalamus and reticular formation. Taken together, these data show that effective habituation to awake fMRI can be achieved by gradual and incremental acclimatization to the experimental conditions. Subsequent BOLD recordings, even during superimposed acoustic stimulation, reflect low stress-levels, low motion and a corresponding high-quality image acquisition. Furthermore, BOLD signals obtained during fMRI indicate that effective habituation facilitates selective attention to sensory stimuli that can in turn support the discrimination of cognitive processes in the absence of stress confounds.