A somato-cognitive action network alternates with effector regions in motor cortex.

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations1,2, despite evidence for concentric functional zones3 and maps of complex actions4. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action5 and physiological control6, arousal7, errors8 and pain9. This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions4 and connectivity to internal organs10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate-isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement.

Structure-function coupling in highly sampled individual brains.

Structural connectivity (SC) between distant regions of the brain support synchronized function known as functional connectivity (FC) and give rise to the large-scale brain networks that enable cognition and behavior. Understanding how SC enables FC is important to understand how injuries to SC may alter brain function and cognition. Previous work evaluating whole-brain SC-FC relationships showed that SC explained FC well in unimodal visual and motor areas, but only weakly in association areas, suggesting a unimodal-heteromodal gradient organization of SC-FC coupling. However, this work was conducted in group-averaged SC/FC data. Thus, it could not account for inter-individual variability in the locations of cortical areas and white matter tracts. We evaluated the correspondence of SC and FC within three highly sampled healthy participants. For each participant, we collected 78 min of diffusion-weighted MRI for SC and 360 min of resting state fMRI for FC. We found that FC was best explained by SC in visual and motor systems, as well as in anterior and posterior cingulate regions. A unimodal-to-heteromodal gradient could not fully explain SC-FC coupling. We conclude that the SC-FC coupling of the anterior-posterior cingulate circuit is more similar to unimodal areas than to heteromodal areas.

Functional characterization of late embryogenesis abundant genes and promoters in pearl millet (Pennisetum glaucum L.) for abiotic stress tolerance.

Late embryogenesis abundant (LEA) genes display distinct functions in response to abiotic stresses in plants. In pearl millet (Pennisetum glaucum L.), a total of 21 PgLEA genes were identified and classified into six groups including LEA1, LEA2, LEA3, LEA5, LEA7, and dehydrins (DHN). Open reading frames (ORFs) of PgLEAs range from 291 bp (PgLEA1-1) to 945 bp (PgLEA2-11) and distributed randomly among the seven chromosomes. Phylogenetic analysis revealed that all PgLEA proteins are closely related to sorghum LEA proteins. The PgLEAs were found to be expressed differentially under high progressive vapor pressure deficit (VPD), PgLEA7 was significantly expressed under high VPD and was selected for functional validation. In silico analysis of the PgLEA promoter regions revealed abiotic stress-specific cis-acting elements such as ABRE, CCAAT, MYBS, and LTRE. Based on the type of motifs, PgLEAPC promoter (758 bp), its deletion 1 (PgLpd1, 349 bp) and deletion 2 (PgLpd2, 125 bp) were cloned into the plant expression vector pMDC164 having the promoter-less uidA gene. All the three plant expression vectors were introduced into tobacco through Agrobacterium tumefaciens-mediated transformation to obtain T1 and T2 generations of transgenic plants. Based on expression of the uidA gene, tissue-specific expression was observed in mature stems, roots and seedlings of PgLEAPC and PgLpd1 carrying transgenics only. While the transgenic PgLEAPC plants displayed significantly higher uidA expression in the stem and root tissues under salt, drought, heat, and cold stresses, very low or no expression was observed in PgLpd1 and PgLpd2 transgenics under the tested stress conditions. The results of this study indicate that the complete promoter of PgLEAPC plays a role in developing abiotic stress tolerance in plants.

Comorbid Conditions Differentiate Rehabilitation Profiles in Traumatic Versus Nontraumatic Brain Injury: A Retrospective Analysis Using a Medical Database.

PURPOSE: We examined the relationship between comorbid medical conditions and changes in cognition over the course of rehabilitation following acquired brain injury. In particular, we compared outcomes between traumatic brain injury (TBI) and non-TBI using a retrospective inpatient rehabilitation dataset. We hypothesized that differences by diagnosis would be minimized among subgroups of patients with common comorbid medical conditions. MATERIALS AND METHODS: We used the Functional Independence Measure (FIM)-cognition subscale to index changes in cognition over rehabilitation. A decision tree classifier determined the top 10 comorbid conditions that maximally differentiated TBI and non-TBI. Ten subsets of patients were identified by matching on these conditions, in rank order. Data from these subsets were submitted to repeated-measures logistic regression to establish the minimum degree of commonality in comorbid conditions that would produce similar cognitive rehabilitation, regardless of etiology. RESULTS: The TBI group demonstrated a greater increase in ordinal scores over time relative to non-TBI, across all subscales of the FIM-cognition. When both groups were matched on the top 3 symptoms, there were no significant group differences in rehabilitation trajectory in problem-solving and memory domains (Cohen's d range: 0.2-0.4). CONCLUSION: Comorbid medical conditions explain differences in cognitive rehabilitation trajectories following acquired brain injury beyond etiology.

Late Midlife Subclinical Infarct Burden and Risk of Dementia: The Atherosclerosis Risk in Communities Neurocognitive Study.

At visit 3 (1993-1995) of the ARIC Study, 1.5T brain MRI was completed in 1,881 stroke-free participants (Mean age = 62.9±4.9, 50% Black). Cox regression examined associations between infarct group [infarct-free (referent; n = 1,611), smaller only (<3 mm; n = 50), larger only (≥3 mm but <20 mm; n = 185), both (n = 35)] and up to 25-year incident dementia (n = 539). Participants with both infarcts were over 2.5 times more likely to develop dementia [HR = 2.61; 95% CI = 1.44, 4.72]. Smaller only (HR = 1.22; 95% CI = 0.70, 2.13) and larger only (HR = 1.27; 95% CI = 0.92, 1.74) groups showed associations with wide confidence intervals, unsupported statistically. A late midlife infarct profile including smaller and larger infarcts may represent particular vulnerability to dementia risk.

Evaluating brain modularity benefits of an acting intervention: a discriminant-analysis framework.

Purpose: Aging is associated with a reduction in brain modularity as well as aspects of executive function, namely, updating, shifting, and inhibition. Previous research has suggested that the aging brain exhibits plasticity. Further, it has been hypothesized that broad-based intervention models may be more effective in eliciting overall gains in executive function than interventions targeted at specific executive skills (e.g., computer-based training). To this end, we designed a 4-week theater-based acting intervention in older adults within an RCT framework. We hypothesized that older adults would show improvements in brain modularity and aspects of executive function, ascribed to the acting intervention. Materials and methods: The participants were 179 adults from the community, aged 60-89 years and on average, college educated. They completed a battery of executive function tasks and resting state functional MRI scans to measure brain network modularity pre- and post-intervention. Participants in the active intervention group (n = 93) enacted scenes with a partner that involved executive function, whereas the active control group (n = 86) learned about the history and styles of acting. Both groups met two times/week for 75-min for 4 weeks. A mixed model was used to evaluate intervention effects related to brain modularity. Discriminant-analysis was used to determine the role of seven executive functioning tasks in discriminating the two groups. These tasks indexed subdomains of updating, switching, and inhibition. Discriminant tasks were subject to a logistic regression analysis to determine how post-intervention executive function performance interacted with changes in modularity to predict group membership. Results: We noted an increase in brain modularity in the acting group, relative to pre-intervention and controls. Performance on updating tasks were representative of the intervention group. However, post-intervention performance on updating did not interact with the observed increase in brain modularity to distinguish groups. Conclusion: An acting intervention can facilitate improvements in modularity and updating, both of which are sensitive to aging and may confer benefits to daily functioning and the ability to learn.

Structure-Function Coupling in Highly Sampled Individual Brains.

Structural connections (SC) between distant regions of the brain support synchronized function known as functional connectivity (FC) and give rise to the large-scale brain networks that enable cognition and behavior. Understanding how SC enables FC is important to understand how injuries to structural connections may alter brain function and cognition. Previous work evaluating whole-brain SC-FC relationships showed that SC explained FC well in unimodal visual and motor areas, but only weakly in association areas, suggesting a unimodal-heteromodal gradient organization of SC-FC coupling. However, this work was conducted in group-averaged SC/FC data. Thus, it could not account for inter-individual variability in the locations of cortical areas and white matter tracts. We evaluated the correspondence of SC and FC within three highly sampled healthy participants. For each participant, we collected 78 minutes of diffusion-weighted MRI for SC and 360 minutes of resting state fMRI for FC. We found that FC was best explained by SC in visual and motor systems, as well as in anterior and posterior cingulate regions. A unimodal-to-heteromodal gradient could not fully explain SC-FC coupling. We conclude that the SC-FC coupling of the anterior-posterior cingulate circuit is more similar to unimodal areas than to heteromodal areas. SIGNIFICANCE STATEMENT: Structural connections between distant regions of the human brain support networked function that enables cognition and behavior. Improving our understanding of how structure enables function could allow better insight into how brain disconnection injuries impair brain function.Previous work using neuroimaging suggested that structure-function relationships vary systematically across the brain, with structure better explaining function in basic visual/motor areas than in higher-order areas. However, this work was conducted in group-averaged data, which may obscure details of individual-specific structure-function relationships.Using individual-specific densely sampled neuroimaging data, we found that in addition to visual/motor regions, structure strongly predicts function in specific circuits of the higher-order cingulate gyrus. The cingulate's structure-function relationship suggests that its organization may be unique among higher-order cortical regions.

Framewise multi-echo distortion correction for superior functional MRI.

Functional MRI (fMRI) data are severely distorted by magnetic field (B0) inhomogeneities which currently must be corrected using separately acquired field map data. However, changes in the head position of a scanning participant across fMRI frames can cause changes in the B0 field, preventing accurate correction of geometric distortions. Additionally, field maps can be corrupted by movement during their acquisition, preventing distortion correction altogether. In this study, we use phase information from multi-echo (ME) fMRI data to dynamically sample distortion due to fluctuating B0 field inhomogeneity across frames by acquiring multiple echoes during a single EPI readout. Our distortion correction approach, MEDIC (Multi-Echo DIstortion Correction), accurately estimates B0 related distortions for each frame of multi-echo fMRI data. Here, we demonstrate that MEDIC's framewise distortion correction produces improved alignment to anatomy and decreases the impact of head motion on resting-state functional connectivity (RSFC) maps, in higher motion data, when compared to the prior gold standard approach (i.e., TOPUP). Enhanced framewise distortion correction with MEDIC, without the requirement for field map collection, furthers the advantage of multi-echo over single-echo fMRI.

Racial and demographic disparities in emergency department utilization for mental health concerns before and during the COVID-19 pandemic.

This study investigated whether emergency department (ED) visits for mental health concerns increased during the COVID-19 pandemic, taking a health disparities lens. ED encounters from the only academic medical center in Mississippi were extracted from March-December 2019 and 2020, totaling 2,842 pediatric (ages 4-17) and 17,887 adult (ages 18-89) patients. Visits were coded based on primary ED diagnosis. For adults, there were fewer depression/anxiety ED visits during the pandemic, not moderated by any demographic factor, but no differences for serious mental illness or alcohol/substance use. For youth, there were significantly fewer ED visits for behavior problems during the pandemic among children in the lower socioeconomic status (SES) category; there were no differences for depression/anxiety. Regardless of year, adults in the lower SES category were more likely to visit the ED for mental health, Black adults were less likely to visit the ED for depression/anxiety or alcohol/substance use, and Black children were less likely to visit the ED for behavioral concerns. Results suggest that access to outpatient and telehealth services remains critical for mental health care during the pandemic and underline the importance of race- and SES-related factors in use of the ED for mental health concerns beyond the pandemic.

Can a Theater Acting Intervention Enhance Inhibitory Control in Older Adults? A Brain-Behavior Investigation.

Purpose: Studies of reactive and proactive modes of inhibitory control tend to show age-related declines and are accompanied by abnormalities in the prefrontal cortex. We explored which mode of inhibitory control would be more amenable to change and accrue greater benefits following engagement in a 4-week theater acting intervention in older adults. These gains were evaluated by performance on the AX-CPT task. We hypothesized that an increase in proactive control would relate to an increase in AY errors and a decrease in BX errors. In contrast, an increase in reactive control would be associated with a decrease in AY errors, no change in AY reaction time, and an increase in BX response time. Further, we posited that an increase in behavioral proactive control would accompany greater cue versus probe activity for previously identified regions in the prefrontal cortex. In contrast, an increase in behavioral reactive control would be accompanied by greater probe activation in these identified brain areas. Materials and Methods: The participants were 179 community-dwelling adults aged 60-89 years who were on average, college-educated. Participants were pseudo-randomly assigned to either an active-experiencing acting intervention condition (n = 93) or the active control condition (n = 86); participant assignment was subject to time of enrollment. Participants in both groups were trained by theater-actor researchers with expertise in acting interventions. In contrast to the active control participants who attended a course on theater acting, the acting-intervention group was required to consistently deploy proactive and reactive control mechanisms. Both groups met two times/week for 75-min for 4 weeks. Participant brain-behavioral performance on the AX-CPT task was evaluated prior to and after this four-week period. Results: No intervention effects were found in favor of proactive control. Behavioral evidence in favor of reactive control was weak. Brain-related benefits to reactive control was illustrated by greater probe-activation in Brodmann areas 6 and 8, relative to controls and pre-intervention. Conclusion: We found some evidence for improvements in reactive control via brain measures, attributed to engagement in the acting intervention.

Differences in Brain Architecture in Remote Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is brain trauma from an external impact with a loss of consciousness less than 30 min. Mild TBI results in several biopsychosocial impairments, with pronounced cognitive deficits thought to resolve within 3 months of injury. Previous research suggests that these impairments are due to a temporary inability to appropriately allocate neural resources in response to cognitive demands. Our study questioned this assumption and instead hypothesized that mTBI was associated with long-term neural disruptions and compromised brain structure integrity. By extension, we investigated the likelihood that functional restitution and cognitive resolution following mTBI may be due to some form of neurofunctional reorganization. To this end, we examined abnormalities in resting state functional connectivity and structure (volume, thickness, and fractional anisotropy) in two groups of mTBI-those with 1-10 years time post-injury (mTBI1-10), and those with 20-65 years time post-injury, relative to age-, sex-, and education-matched controls. We observed abnormalities in brain architecture only in the mTBI1-10 group, characterized by functional hypo-activation in the right frontal pole, smaller frontal pole volume, and lesser fractional anisotropy in the genu of the corpus callosum that extended near the right frontal pole. This frontal region is laterally specialized to regulate function specific to socio-emotional processes. Collectively, neural disruptions and structural insult in mTBI may persist up to 10 years following injury, but injury-related pathology may resolve with longer recovery time. Disruption to frontal-dependent function that supports socio-emotional processes also may interfere with cognitive functioning, as in the case of chronic mTBI.