Information flow between interacting human brains: Identification,validation, and relationship to social expertise

Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender’s and receiver’s temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions.Human social interactions have likely shaped brain evolution and are critical for development, health, and society. Defining their neural underpinnings is a key goal of social neuroscience. Interacting dyads, the simplest and fundamental form of human interaction, have been examined with behavioral setups that used real movement interactions during communication in real time as a proxy (1–4), providing mathematical models representing human interaction, goal sharing, mutual engagement, and coordination. To identify the neural systems supporting these behaviors, neuroimaging would be the tool of choice, but studying dyadic interactions with this method is both experimentally and analytically challenging. Consequently, the neural processes underlying human social interactions remain incompletely understood.Experimentally, studying dyads with neuroimaging technology that allows only one participant per scanner provides challenges that have been addressed in the literature in one of two ways. First, the audiovisual experiences of human social contact have been simulated using stimuli such as photographs, recorded videos, or computerized avatars in the absence of human interaction (5–7), or, recently, immersive audiovisual linkups have been used with one of the two participants being scanned (8, 9). Secondly, pioneering neuroimaging experiments have coupled two scanner sites over the Internet, a setup called hyperscanning, enabling subjects to observe higher-level behavioral responses such as choices made to accept or reject an offer in real time while in the scanners (10, 11). In the current study, we aimed to combine the advantages of these experimental approaches by enabling two humans to see (and possibly hear) each other in a hyperscanning framework, enabling an immersive social interaction while both participant’s brains are imaged. To do so, we implemented a setup with delay-free data transmission and precisely synchronized data acquisition, in addition to a live video stream provided between scanner sites during the entire session (Fig. 1A). While real-time video transmission is not an indispensable requirement for the study of all forms of social interaction, it is a naturalistic presentation method for visual social stimuli in the scanner, and likely helpful for the study of interactions involving changes in eye gaze and facial expressions, although the advantages of the precise temporal synchronization are partially mitigated by the low temporal resolution of the blood oxygen level-dependent (BOLD) response and the sampling frequency of functional MRI (fMRI) experiments.Open in a separate windowFig. 1.Hardware environment and analysis routine for fMRI hyperscanning. (A) Illustration of the hyperscanning setup as implemented for the present studies. (B) Schematic overview of the analysis routine for the examination of information flow between interacting human brain systems in hyperscanned fMRI data. Letters correspond to the numbering of in-text analysis steps.Analytically, extracting and testing for information flow in the resulting joint neuroimaging data are not straightforward. In this paper, we describe a general analysis framework for this problem that makes only minimal a priori assumptions. Importantly, using permutation testing, we also aim to address the open question of whether there is anything neurally specific or even unique about human dyadic interaction, compared with a situation in which no real-time information is exchanged.In the current paper, we study joint attention (JA), a basic yet fundamental mechanism of social interaction that is used by humans to coordinate and communicate intentions and information as well as guiding others’ attention in a nonverbal way, especially through eye gaze (12). JA is of considerable interest both for cognitive and clinical neuroscience because it arises early in development, preceding and shaping the emergence of symbolic communication and higher-order social functions such as representational theory of mind (13, 14). Disturbances of JA in developmental disorders with prominent social disturbances such as autism and attention deficit hyperactivity disorder, but also schizophrenia, have been identified (see, e.g., refs. 13 and 15).To investigate JA, we used a paradigm where information on a target location is given to one subject (sender of information) only, but both subjects (sender and receiver) must respond correctly by indicating the target location on a button response device. Thus, information needs to be transferred from one subject to another nonverbally while fMRI data are acquired, resulting in flow of information between two interacting brain systems (interaction phase, INT). For determination of interaction-based aspects of the fMRI data, control phases without interaction were added to the task protocol (NoINT). We studied a discovery sample to identify the main neural parameters of information flow (n = 26) and, for confirmation, a larger independent replication sample (n = 50). Combined, these data were used to validate the approach and relate the resulting parameters to socially relevant psychometric measures. Based on the previous literature on neuroimaging in JA, we expected that we would see information flow involving the temporoparietal junction and medial prefrontal cortex. However, to keep methodological assumptions in this new field minimal, we decided to not include this as an a priori hypothesis into our analysis.     

Neuromuscular Electrical Stimulation–Induced Resistance Training After SCI: A Review of the Dudley Protocol

Background:

Neuromuscular electrical stimulation (NMES), often referred to as functional electrical stimulation (FES), has been used to activate paralyzed skeletal muscle in people with spinal cord injury (SCI). The goal of NMES has been to reverse some of the dramatic losses in skeletal muscle mass, to stimulate functional improvements in people with incomplete paralysis, and to produce some of the health benefits associated with exercise.

Objective:

The purpose of this brief review is to describe a quantifiable resistance training form of NMES developed by Gary A. Dudley.

Methods:

People with motor complete SCI were first tested to confirm that an NMES-induced muscle contraction of the quadriceps muscle could be achieved. The contraction stimulus consisted of biphasic pulses at 35 Hz performed with increasing current up to what was needed to produce full knee extension. Four sets of 10 knee extensions were elicited, if possible. Training occurred biweekly for 3 to 6 months, with ankle weights being increased up to an added weight of 9.1 kg if the 40 repetitions could be performed successfully for 2 sessions.

Results:

Many participants have performed this protocol without adverse events, and all participants showed progression in the number of repetitions and/or the amount of weight lifted. Large increases in muscle mass occur, averaging 30% to 40%. Additional physiological adaptations to stimulated muscle have also been reported.

Conclusions:

These results demonstrate that the affected skeletal muscle after SCI responds robustly to progressive resistance training many years after injury. Future work with NMES should determine whether gains in lean mass translate to improved health, function, and quality of life.Key words: electrical stimulation, muscle hypertrophy, spinal cord injuryIn the past few years, there have been significant advances in the management of people with spinal cord injury (SCI). New treatments such as stem cell therapies,¹ epidural stimulation,² and exoskeletons³ are showing great potential. Unfortunately, many people living with an SCI will not be able to take advantage of new treatments or the treatments may not be as effective at restoring their function because they have such deteriorated musculoskeletal systems. Currently, most rehabilitation treatments focus on compensating for lost function to increase independence in activities of daily living and neglect the musculoskeletal system. Therefore, rehabilitation interventions to preserve and/or restore the musculoskeletal system are critical for individuals with SCI to lead healthier lives and possibly take advantage of future, innovative treatments.The consequences of SCI on the musculoskeletal system are quite devastating. Skeletal muscle is perhaps one of the most important tissues in human physiology, comprising approximately 40% of body mass and accounting for much of total energy expenditure. There are multiple adaptations that occur at the skeletal muscle level that have been documented. People with SCI suffer substantial muscle atrophy⁴ and altered body composition,⁵ which likely contribute to their increased susceptibility to secondary complications.^6,7 Although considerable evidence has been compiled in animal models, we focus on relevant human studies. The early work in the late 1970s reported significant myofiber atrophy and a predominantly fast composition as compared to able-bodied counterparts.^8–10 Longitudinal studies on the topic have been less abundant, but Burnham et al¹¹ reported on serial biopsy samples in a few participants and Castro et al¹² provided a detailed analysis after acute SCI, showing rapid losses in myofiber size with fibers approximately 60% the size of able-bodied controls and continuing atrophy for 18 more weeks. Studies of whole muscle with current imaging techniques show rapid skeletal muscle loss as evidenced by MRI early after injury⁴ or a significant difference in muscle mass in people several years after SCI.¹³Of the countermeasures for muscle atrophy tested to date, including pharmacologic therapies and various modes of exercise training, only intense resistance exercise training has consistently been found to effectively increase muscle mass. Previous studies have shown that the muscles of people after SCI respond to neuromuscular electrical stimulation (NMES) contractions with some degree of adaptation. These studies used what has been termed functional electrical stimulation (FES), which often consists of pedaling a cycle ergometer or performing a walking exercise. When participants perform FES cycling, it is difficult to quantify the mixture of resistance and endurance exercise stimuli. Tetanic concentric contractions are performed by the various muscles in the leg, but once the participant can no longer reach the target work level, the device may move the limbs passively or the session is complete. Most studies using FES training report modest hypertrophy of about 10% to 12%.^14–16 However, one study that lasted 12 months (training up to 5 days per week for 60 minutes) reported increases in thigh muscle cross-sectional area of 35.5% ± 18%.¹⁷ In 1999, Gary A. Dudley’s (Figure 1) laboratory published a short paper on a simple, innovative intervention that utilized NMES in combination with progressive resistance training principles to yield remarkable skeletal muscle hypertrophy in affected muscle after SCI.¹⁸ Dudley’s group effectively reversed 48 weeks of atrophy in the quadriceps femoris with a short intervention that was conducted 2 days per week for 8 weeks. Open in a separate windowFigure 1.Gary A. Dudley, PhD, evaluates MRIs of the thigh. The picture was taken at the University of Georgia around 1998.Since the initial paper from Dudley, we^19,20 and others²¹ have utilized this simple, home-based NMES-induced resistance training program to evoke substantial skeletal muscle hypertrophy. In these studies, quadriceps femoris cross-sectional area (CSA), measured by MRI, was increased by about 35% in just 12 weeks. For comparison, studies in able-bodied individuals, using similar imaging techniques, have reported increases in CSA of about 10% to 15% when using NMES^22,23 or voluntary actions.²⁴ In this short review, we detail the methodology and highlight data from published and previously unpublished work to support the use of this type of training for inducing robust increases in skeletal muscle mass in people with SCI.We report data from 3 studies that utilized the same methodology to evoke skeletal muscle hypertrophy in participants with SCI. Portions of study 1 have previously been published (n = 14)²⁰; study 2 was conducted over the course of 6 months (n = 6), with a 3-month subset (n = 5) previously published¹⁹; and study 3 was recently completed over 8 weeks (n = 6). Participants in all studies provided written, informed consent, and all studies were approved by the appropriate institutional review boards (University of Alabama at Birmingham or University of Georgia).     

Receptors for pro‐resolving mediators are increased in Alzheimer's disease brain

Neuroinflammation is a key element of AD pathology and conceivably a result of a disturbed resolution. Resolution of inflammation is an active process which is strictly orchestrated following the acute inflammatory response after removal of the inflammatory stimuli. Acute inflammation is actively terminated by specialized pro‐resolving mediators (SPMs) thereby promoting healing and return to homeostasis. Failed resolution may contribute to persistent neuroinflammation and aggravate AD pathology. BLT1 (leukotriene B₄ receptor) and ChemR23 (chemerin receptor 23) are receptors for the SPM resolvin (Rv) E1 and are important clinical targets for ending inflammation. In AD, the levels of SPMs are decreased, and pro‐inflammatory mediators are increased. In the current study, the distribution of BLT1 and ChemR23 receptors in control brains and in AD as well as correlations with AD pathology was examined for the first time. BLT1 and ChemR23 were analyzed in different regions of post‐mortem human brain from cases with AD, early‐onset AD and mild cognitive impairment (MCI) and healthy controls, using western blotting and immunohistochemistry. BLT1 and ChemR23 were detected in neurons and glial cells in all examined regions of the human brain, with markedly higher levels in AD than in controls. The receptor levels correlated with the density of staining for the inflammation markers HLA‐DR and YKL‐40 for microglia and astrocytes, respectively, and elevated staining coincided with high Braak stages in AD. The relative staining densities of these receptors were higher in the basal forebrain, cingulate gyrus and hippocampal regions compared to the cerebellum and frontal cortex (BA46). In conclusion, alterations in the expression of the resolution receptor BLT1 in AD have not been reported previously and the changes in both BLT1 and ChemR23 suggest a disturbed resolution pathway in several regions of the AD brain that may play a role in disease pathology.     

Modified coronally advanced tunnel versus epithelialized free gingival graft technique in gingival phenotype modification: a comparative randomized controlled clinical trial

Clinical Oral Investigations - The gingival thickness (GT) and keratinized tissue (KT) height are defined as the gingival phenotype. Both the modified coronally advanced tunnel technique (MCAT) and...     

Double filtration plasmapheresis for a case of Crimean-Congo hemorrhagic fever

Crimean-Congo hemorrhagic fever (CCHF), is a fatal viral infection transmitted to humans through a tick bite or exposure to blood or tissues of viremic hosts. The clinical presentation is characterized by sudden onset high fever, headache, myalgia, abdominal pain and nausea–vomiting followed by gastrointestinal, urinary, respiratory tract and brain hemorrhage. Laboratory findings include leucopenia, thrombocytopenia, elevated liver enzymes, prolonged prothrombin time and activated partial thromboplastin time. We report a case of CCHF who was treated with a combination of DFPP and ribavirin therapy. As a result of this multimodal treatment, patient’s clinical symptoms and laboratory findings improved gradually.