Cortical networks show characteristic recruitment patterns after somatosensory stimulation by pneumatically evoked repetitive hand movements in newborn infants.

Controlled assessment of functional cortical networks is an unmet need in the clinical research of noncooperative subjects, such as infants. We developed an automated, pneumatic stimulation method to actuate naturalistic movements of an infant's hand, as well as an analysis pipeline for assessing the elicited electroencephalography (EEG) responses and related cortical networks. Twenty newborn infants with perinatal asphyxia were recruited, including 7 with mild-to-moderate hypoxic-ischemic encephalopathy (HIE). Statistically significant corticokinematic coherence (CKC) was observed between repetitive hand movements and EEG in all infants, peaking near the contralateral sensorimotor cortex. CKC was robust to common sources of recording artifacts and to changes in vigilance state. A wide recruitment of cortical networks was observed with directed phase transfer entropy, also including areas ipsilateral to the stimulation. The extent of such recruited cortical networks was quantified using a novel metric, Spreading Index, which showed a decrease in 4 (57%) of the infants with HIE. CKC measurement is noninvasive and easy to perform, even in noncooperative subjects. The stimulation and analysis pipeline can be fully automated, including the statistical evaluation of the cortical responses. Therefore, the CKC paradigm holds great promise as a scientific and clinical tool for controlled assessment of functional cortical networks.

MEG Insight into the Spectral Dynamics Underlying Steady Isometric Muscle Contraction.

To gain fundamental knowledge on how the brain controls motor actions, we studied in detail the interplay between MEG signals from the primary sensorimotor (SM1) cortex and the contraction force of 17 healthy adult humans (7 females, 10 males). SM1 activity was coherent at ∼20 Hz with surface electromyogram (as already extensively reported) but also with contraction force. In both cases, the effective coupling was dominant in the efferent direction. Across subjects, the level of ∼20 Hz coherence between cortex and periphery positively correlated with the "burstiness" of ∼20 Hz SM1 (Pearson r ≈ 0.65) and peripheral fluctuations (r ≈ 0.9). Thus, ∼20 Hz coherence between cortex and periphery is tightly linked to the presence of ∼20 Hz bursts in SM1 and peripheral activity. However, the very high correlation with peripheral fluctuations suggests that the periphery is the limiting factor. At frequencies <3 Hz, both SM1 signals and ∼20 Hz SM1 envelope were coherent with both force and its absolute change rate. The effective coupling dominated in the efferent direction between (1) force and the ∼20 Hz SM1 envelope and (2) the absolute change rate of the force and SM1 signals. Together, our data favor the view that ∼20 Hz coherence between cortex and periphery during isometric contraction builds on the presence of ∼20 Hz SM1 oscillations and needs not rely on feedback from the periphery. They also suggest that effective cortical proprioceptive processing operates at <3 Hz frequencies, even during steady isometric contractions.SIGNIFICANCE STATEMENT Accurate motor actions are made possible by continuous communication between the cortex and spinal motoneurons, but the neurophysiological basis of this communication is poorly understood. Using MEG recordings in humans maintaining steady isometric muscle contractions, we found evidence that the cortex sends population-level motor commands that tend to structure according to the ∼20 Hz sensorimotor rhythm, and that it dynamically adapts these commands based on the <3 Hz fluctuations of proprioceptive feedback. To our knowledge, this is the first report to give a comprehensive account of how the human brain dynamically handles the flow of proprioceptive information and converts it into appropriate motor command to keep the contraction force steady.

Corticokinematic coherence as a new marker for somatosensory afference in newborns.

OBJECTIVE: Somatosensory evoked potentials have high prognostic value in neonatal intensive care, but their recording from infants is challenging. Here, we studied the possibility to elicit cortical responses in newborns by simple passive hand movements. METHODS: We examined 13 newborns (postnatal age 1-46days) during clinically indicated 19-channel electroencephalography (EEG) recordings in the neonatal intensive care unit; EEG indications included birth asphyxia and suspected epileptic seizures. The experimenter moved the infant's wrist or fingers at 1 or 2Hz for 5-10min, separately on both sides. We measured movement kinematics with an accelerometer attached to the infant's hand and computed coherence between the EEG and acceleration signals (corticokinematic coherence, CKC). RESULTS: Statistically significant CKC (amplitude 0.020-0.511) with characteristic scalp topography was observed in all infants at twice the movement frequency. CKC was contralaterally dominant on the central scalp (median laterality index 0.48 for right-hand and -0.63 for left-hand movements). CONCLUSIONS: Passive movements elicit cortical responses that can be readily observed in clinical EEG recordings from newborns in the intensive-care environment. SIGNIFICANCE: CKC is a novel, noninvasive marker for the somatosensory system. Its robustness and practical ease make it attractive for bedside assessment of neurologically compromised newborns.

Effect of interstimulus interval on cortical proprioceptive responses to passive finger movements.

Shortening of the interstimulus interval (ISI) generally leads to attenuation of cortical sensory responses. For proprioception, however, this ISI effect is still poorly known. Our aim was to characterize the ISI dependence of movement-evoked proprioceptive cortical responses and to find the optimum ISI for proprioceptive stimulation. We measured, from 15 healthy adults, magnetoencephalographic responses to passive flexion and extension movements of the right index finger. The movements were generated by a movement actuator at fixed ISIs of 0.5, 1, 2, 4, 8, and 16 s, in separate blocks. The responses peaked at ~ 70 ms (extension) and ~ 90 ms (flexion) in the contralateral primary somatosensory cortex. The strength of the cortical source increased with the ISI, plateauing at the 8-s ISI. Modeling the ISI dependence with an exponential saturation function revealed response lifetimes of 1.3 s (extension) and 2.2 s (flexion), implying that the maximum signal-to-noise ratio (SNR) in a given measurement time is achieved with ISIs of 1.7 s and 2.8 s respectively. We conclude that ISIs of 1.5-3 s should be used to maximize SNR in recordings of proprioceptive cortical responses to passive finger movements. Our findings can benefit the assessment of proprioceptive afference in both clinical and research settings.

Haptic contents of a movie dynamically engage the spectator's sensorimotor cortex.

Observation of another person's actions and feelings activates brain areas that support similar functions in the observer, thereby facilitating inferences about the other's mental and bodily states. In real life, events eliciting this kind of vicarious brain activations are intermingled with other complex, ever-changing stimuli in the environment. One practical approach to study the neural underpinnings of real-life vicarious perception is to image brain activity during movie viewing. Here the goal was to find out how observed haptic events in a silent movie would affect the spectator's sensorimotor cortex. The functional state of the sensorimotor cortex was monitored by analyzing, in 16 healthy subjects, magnetoencephalographic (MEG) responses to tactile finger stimuli that were presented once per second throughout the session. Using canonical correlation analysis and spatial filtering, consistent single-trial responses across subjects were uncovered, and their waveform changes throughout the movie were quantified. The long-latency (85-175 ms) parts of the responses were modulated in concordance with the participants' average moment-by-moment ratings of own engagement in the haptic content of the movie (correlation r = 0.49; ratings collected after the MEG session). The results, obtained by using novel signal-analysis approaches, demonstrate that the functional state of the human sensorimotor cortex fluctuates in a fine-grained manner even during passive observation of temporally varying haptic events. Hum Brain Mapp 37:4061-4068, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Phasic stabilization of motor output after auditory and visual distractors.

To maintain steady motor output, distracting sensory stimuli need to be blocked. To study the effects of brief auditory and visual distractors on the human primary motor (M1) cortex, we monitored magnetoencephalographic (MEG) cortical rhythms, electromyogram (EMG) of finger flexors, and corticomuscular coherence (CMC) during right-hand pinch (force 5-7% of maximum) while 1-kHz tones and checkerboard patterns were presented for 100 ms once every 3.5-5 s. Twenty-one subjects (out of twenty-two) showed statistically significant ∼20-Hz CMC. Both distractors elicited a covert startle-like response evident in changes of force and EMG (∼50% of the background variation) but without any visible movement, followed by ∼1-s enhancement of CMC (auditory on average by 75%, P < 0.001; visual by 33%, P < 0.05) and rolandic ∼20-Hz rhythm (auditory by 14%, P < 0.05; visual by 11%, P < 0.01). Directional coupling of coherence from muscle to the M1 cortex (EMG→MEG) increased for ∼0.5 s at the onset of the CMC enhancement, but only after auditory distractor (by 105%; P < 0.05), likely reflecting startle-related proprioceptive afference. The 20-Hz enhancements occurred in the left M1 cortex and were for the auditory stimuli preceded by an early suppression (by 7%, P < 0.05). Task-unrelated distractors modulated corticospinal coupling at ∼20 Hz. We propose that the distractors triggered covert startle-like responses, resulting in proprioceptive afference to the cortex, and that they also transiently disengaged the subject's attention from the fine-motor task. As a result, the corticospinal output was readjusted to keep the contraction force stable.

Cigarette smoking and alcohol use as predictors of disability retirement: A population-based cohort study.

BACKGROUND: This study investigated how cigarette smoking and alcohol use predict disability retirement. METHODS: Data from the longitudinal nationwide Finnish Twin Cohort study were analyzed, with clustered study design applied when computing 95% confidence intervals (CI). The sample included 21,719 individuals. Smoking and alcohol use were assessed with a questionnaire in 1975. Registry data on retirement events up till end of 2004 were obtained from the Social Insurance Institution and the Finnish Centre for Pensions. RESULTS: Disability pension was granted to 4251 participants. Among men, adjusted for age and alcohol use, former (HR=1.45, 95%CI 1.28, 1.65, p<.001) and daily smokers (HR=1.93, 95%CI 1.71, 2.17, p<.001) showed elevated disability pension risk compared to never smokers. Among women, daily smokers (HR=1.25, 95%CI 1.11, 1.40, <.001) had elevated risk. The age and smoking adjusted risk estimates for alcohol were elevated among abstainers (men HR=1.41, 95%CI 1.21, 1.65, p<.001; women HR=1.36, 95%CI 1.23, 1.52, p<.001) and heavy drinkers (men HR=1.30, 95%CI 1.18, 1.43, p<.001; women HR=1.34, 95%CI 1.04, 1.72, p=.026). Those being persistent smokers and binge drinkers had over three-fold disability risk compared to those who were binge drinkers but had only a few smoking years (men: HR=3.32, 95%CI 2.43, 4.54, p<.001; women: HR=4.05, 95%CI 2.05, 8.00, p<.001). Among men and women who were not binge drinkers, longer smoking duration was needed for elevated disability risk. CONCLUSIONS: Both smoking and excess alcohol use significantly predict disability retirement. In order to extend working careers, more attention should be paid to health behaviors, in addition to working conditions.

Lymphopenia-induced proliferation in the absence of functional Autoimmune regulator (Aire) induces colitis in mice.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in Autoimmune regulator (Aire), a transcriptional regulator of negative selection in thymus. However, Aire is also expressed in periphery, but the full range of Aire's peripheral function is unknown. Here, we transferred lymphocytes from wildtype donors into lymphopenic recipients with or without functional Aire. Following cell proliferation thus took place in Aire-sufficient or deficient environment. The wildtype lymphocytes hyperproliferated and induced disease in lymphopenic Aire(-/-) but not in Aire(+/+) recipients. The disease was characterized by diarrhea, inflammation, and colitis, and in some recipients pancreatitis, gastritis, and hepatitis was also found. Our results identify Aire as an important regulator of peripheral T cell homeostasis in gastrointestinal tissues. Given a suitable trigger the absence of peripheral Aire leads to dysregulated T cell proliferation and disease.

Human primary motor cortex is both activated and stabilized during observation of other person's phasic motor actions.

When your favourite athlete flops over the high-jump bar, you may twist your body in front of the TV screen. Such automatic motor facilitation, 'mirroring' or even overt imitation is not always appropriate. Here, we show, by monitoring motor-cortex brain rhythms with magnetoencephalography (MEG) in healthy adults, that viewing intermittent hand actions of another person, in addition to activation, phasically stabilizes the viewer's primary motor cortex, with the maximum of half a second after the onset of the seen movement. Such a stabilization was evident as enhanced cortex-muscle coherence at 16-20 Hz, despite signs of almost simultaneous suppression of rolandic rhythms of approximately 7 and 15 Hz as a sign of activation of the sensorimotor cortex. These findings suggest that inhibition suppresses motor output during viewing another person's actions, thereby withholding unintentional imitation.