Social and behavioral science at the forefront of genomics: Discovery, translation, and health equity.

This special issue highlights the unique role that social and behavioral science has to play at the forefront of genomics. Through the introduction of papers comprising this special issue, we outline priority research areas at the nexus of genomics and the social and behavioral sciences. These include: Discovery science; clinical and community translation, and equity, including engagement and inclusion of diverse populations in genomic science. We advocate for genomic discovery that considers social context, neural, cognitive, and behavioral endophenotypes, and that is grounded in social and behavioral science research and theory. Further, the social and behavioral sciences should play a leadership role in identifying best practices for effective clinical and community translation of genomic discoveries. Finally, inclusive research that engages diverse populations is necessary for genomic discovery and translation to benefit all. We also highlight ways that genomics can be a fruitful testbed for the development and refinement of social and behavioral science theory. Indeed, an expanded ecological lens that runs from genomes to society will be required to fully understand human behavior.

Defining the Neural Substrate of the Adult Outcome of Childhood ADHD: A Multimodal Neuroimaging Study of Response Inhibition.

OBJECTIVE: Understanding the neural processes tied to the adult outcome of childhood attention deficit hyperactivity disorder (ADHD) could guide novel interventions to improve its clinical course. It has been argued that normalization of prefrontal cortical activity drives remission from ADHD, while anomalies in subcortical processes are "fixed," present even in remission. Using multimodal neuroimaging of inhibitory processes, the authors tested these hypotheses in adults followed since childhood, contrasting remitted against persistent ADHD. METHOD: Adult participants (persistent ADHD, N=35; remit-ted ADHD, N=47; never affected, N=99) were scanned with functional MRI (fMRI) (N=85), magnetoencephalography (N=33), or both (N=63) during a response inhibition task. RESULTS: In fMRI analyses, during inhibition, right caudate anomalies reflected a childhood ADHD history and were present even among those who remitted. By contrast, differences related to adult outcome emerged in cortical (right inferior frontal and inferior parietal/precuneus) and cerebellar regions. The persistent ADHD group showed under-activation, whereas the remitted ADHD group did not differ significantly from the never-affected group. Magnetoencephalography showed that the association between adult symptom severity and prefrontal neuronal activity was confined to the time window covering the act of inhibition (300 ms-350 ms). Group differences in cerebellar and parietal neuronal activity occurred during the time window of performance monitoring processes (500 ms-600 ms). CONCLUSIONS: By combining fMRI and magnetoencephalography, the location and time window of neuronal activity that underpins the adult outcome of ADHD was pinpointed. Thus, the cortico-cerebellar processes tied to the clinical course of ADHD are separated from the subcortical processes that are not.

Motor-related brain activity during action observation: a neural substrate for electrocorticographic brain-computer interfaces after spinal cord injury.

After spinal cord injury (SCI), motor commands from the brain are unable to reach peripheral nerves and muscles below the level of the lesion. Action observation (AO), in which a person observes someone else performing an action, has been used to augment traditional rehabilitation paradigms. Similarly, AO can be used to derive the relationship between brain activity and movement kinematics for a motor-based brain-computer interface (BCI) even when the user cannot generate overt movements. BCIs use brain signals to control external devices to replace functions that have been lost due to SCI or other motor impairment. Previous studies have reported congruent motor cortical activity during observed and overt movements using magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). Recent single-unit studies using intracortical microelectrodes also demonstrated that a large number of motor cortical neurons had similar firing rate patterns between overt and observed movements. Given the increasing interest in electrocorticography (ECoG)-based BCIs, our goal was to identify whether action observation-related cortical activity could be recorded using ECoG during grasping tasks. Specifically, we aimed to identify congruent neural activity during observed and executed movements in both the sensorimotor rhythm (10-40 Hz) and the high-gamma band (65-115 Hz) which contains significant movement-related information. We observed significant motor-related high-gamma band activity during AO in both able-bodied individuals and one participant with a complete C4 SCI. Furthermore, in able-bodied participants, both the low and high frequency bands demonstrated congruent activity between action execution and observation. Our results suggest that AO could be an effective and critical procedure for deriving the mapping from ECoG signals to intended movement for an ECoG-based BCI system for individuals with paralysis.

Characterizing global statistical significance of spatiotemporal hot spots in magnetoencephalography/ electroencephalography source space via excursion algorithms.

Identifying brain regions with high differential response under multiple experimental conditions is a fundamental goal of functional imaging. In many studies, regions of interest (ROIs) are not determined a priori but are instead discovered from the data, a process that requires care because of the great potential for false discovery. An additional challenge is that magnetoencephalography/electroencephalography sensor signals are very noisy, and brain source images are usually produced by averaging sensor signals across trials. As a consequence, for a given subject, there is only one source data vector for each condition, making it impossible to apply testing methods such as analysis of variance. We solve these problems in several steps. (1) To obtain within-condition uncertainty, we apply the bootstrap across trials, producing many bootstrap source images. To discover 'hot spots' in space and time that could become ROIs, (2) we find source locations where likelihood ratio statistics take unusually large values. We are not interested in isolated brain locations where a test statistic might happen to be large. Instead, (3) we apply a clustering algorithm to identify sources that are contiguous in space and time where the test statistic takes an 'excursion' above some threshold. Having identified possible spatiotemporal ROIs, (4) we evaluate global statistical significance of ROIs by using a permutation test. After these steps, we check performance via simulation, and then illustrate their application in a magnetoencephalography study of four-direction center-out wrist movement, showing that this approach identifies statistically significant spatiotemporal ROIs in the motor and visual cortices of individual subjects.

Decoding semantic information from human electrocorticographic (ECoG) signals.

This study examined the feasibility of decoding semantic information from human cortical activity. Four human subjects undergoing presurgical brain mapping and seizure foci localization participated in this study. Electrocorticographic (ECoG) signals were recorded while the subjects performed simple language tasks involving semantic information processing, such as a picture naming task where subjects named pictures of objects belonging to different semantic categories. Robust high-gamma band (60-120 Hz) activation was observed at the left inferior frontal gyrus (LIFG) and the posterior portion of the superior temporal gyrus (pSTG) with a temporal sequence corresponding to speech production and perception. Furthermore, Gaussian Naïve Bayes and Support Vector Machine classifiers, two commonly used machine learning algorithms for pattern recognition, were able to predict the semantic category of an object using cortical activity captured by ECoG electrodes covering the frontal, temporal and parietal cortices. These findings have implications for both basic neuroscience research and development of semantic-based brain-computer interface systems (BCI) that can help individuals with severe motor or communication disorders to express their intention and thoughts.

Decoding and cortical source localization for intended movement direction with MEG.

Magnetoencephalography (MEG) enables a noninvasive interface with the brain that is potentially capable of providing movement-related information similar to that obtained using more invasive neural recording techniques. Previous studies have shown that movement direction can be decoded from multichannel MEG signals recorded in humans performing wrist movements. We studied whether this information can be extracted without overt movement of the subject, because the targeted users of brain-controlled interface (BCI) technology are those with severe motor disabilities. The objectives of this study were twofold: 1) to decode intended movement direction from MEG signals recorded during the planning period before movement onset and during imagined movement and 2) to localize cortical sources modulated by intended movement direction. Ten able-bodied subjects performed both overt and imagined wrist movement while their cortical activities were recorded using a whole head MEG system. The intended movement direction was decoded using linear discriminant analysis and a Bayesian classifier. Minimum current estimation (MCE) in combination with a bootstrapping procedure enabled source-space statistical analysis, which showed that the contralateral motor cortical area was significantly modulated by intended movement direction, and this modulation was the strongest ∼100 ms before the onset of overt movement. These results suggest that it is possible to study cortical representation of specific movement information using MEG, and such studies may aid in presurgical localization of optimal sites for implanting electrodes for BCI systems.