Somatosensory and motor representations following bilateral transplants of the hands: A 6-year longitudinal case report on the first pediatric bilateral hand transplant patient.

A vascularized composite tissue allotransplantation (VCA) was performed at the Children's Hospital of Philadelphia (CHOP), on an 8-year-old patient in 2015, six years after bilateral hand and foot amputation. Hand VCA resulted in reafferentation of the medial, ulnar, and radial nerves serving hand somatosensation and motor function. We used magnetoencephalography (MEG) to assess somatosensory cortical plasticity following the post-transplantation recovery of the peripheral sensory nerves of the hands. Our 2-year postoperative MEG showed that somatosensory lip representations, initially observed at "hand areas", reverted to canonical, orthotopic lip locations with recovery of post-transplant hand function. Here, we continue the assessment of motor and somatosensory responses up to 6-years post-transplant. Magnetoencephalographic somatosensory responses were recorded eight times over a six-year period following hand transplantation, using a 275-channel MEG system. Somatosensory tactile stimuli were presented to the right lower lip (all 8 visits) as well as right and left index fingers (visits 3-8) and fifth digits (visits 4-8). In addition, left and right-hand motor responses were also recorded for left index finger and right thumb (visit 8 only).During the acute recovery phase (visits 3 and 4), somatosensory responses of the digits were observed to be significantly larger and more phasic (i.e., smoother) than controls. Subsequent measures showed that digit responses maintain this atypical response profile (evoked-response magnitudes typically exceed 1 picoTesla). Orthotopic somatosensory localization of the lip, D2, and D5 was preserved. Motor beta-band desynchrony was age-typical in localization and response magnitude; however, the motor gamma-band response was significantly larger than that observed in a reference population.These novel findings show that the restoration of somatosensory input of the hands resulted in persistent and atypically large cortical responses to digit stimulation, which remain atypically large at 6 years post-transplant; there is no known perceptual correlate, and no reports of phantom pain. Normal somatosensory organization of the lip, D2, and D5 representation remain stable following post-recovery reorganization of the lip's somatosensory response.

Sex differences in sensorimotor mu rhythms during selective attentional processing.

We used magnetoencephalography to investigate the effect of directed attention on sensorimotor mu (8-12 Hz) response (mu reactivity) to non-painful electrical stimulation of the median nerve in healthy adults. Mu desynchronization in the 10-12 Hz bandwidth is typically observed during higher-order cognitive functions including selective attentional processing of sensorimotor information (Pfurtscheller, Neuper, & Krauz, 2000). We found attention-related sex differences in mu reactivity, with females showing (i) prolonged mu desynchrony when attending to somatosensory stimuli, (ii) attentional modulation of the mu response based on whether attention was directed towards or away from somatosensory stimuli, which was absent in males, and (iii) a trend for greater neuronal excitability of the primary somatosensory region suggesting greater physiological responsiveness to sensory stimulation overall. Our findings suggest sex differences in attentional control strategies when processing somatosensory stimuli, whose salience may be greater for females. These sex differences in attention to somatosensory stimuli may help elucidate the well-documented sex biases in pain processing wherein females typically report greater sensitivity to experimental and clinical pain.

Cortical dynamics of selective attention to somatosensory events.

Recent studies have shown evidence of somatosensory deficits in individuals with attentional difficulties yet relatively little is known about the role of attention in the processing of somatosensory input. Neuromagnetic imaging studies have shown that rhythmic oscillations within the human somatosensory cortex are strongly modulated by somatosensory stimulation and may reflect the normal processing of such stimuli. However, few studies have examined how attention influences these cortical oscillations. We examined attentional effects on human somatosensory oscillations during median nerve stimulation by conducting time-frequency analyses of neuromagnetic recordings in healthy adults. We found that selective attention modulated somatosensory oscillations in the alpha, beta, and gamma bands that were both phase-locked and non-phase-locked to the stimulus. In the primary somatosensory cortex (SI), directing the subject's attention toward the somatosensory stimulus resulted in increased gamma band power (30-55 Hz) that was phase-locked to stimulus onset. Directed attention also produced an initial suppression (desynchrony) followed by enhancement (synchrony) of beta band power (13-25 Hz) that was not phase-locked to the stimulus. In the secondary somatosensory cortex (SII), directing attention towards the stimulus increased phase-locked alpha (7-9 Hz) power approximately 30 ms after onset of phase-locked gamma in SI, followed by a non-phase-locked increase in alpha power. We suggest that earlier phase-locked oscillatory power may reflect the relay of input from SI to SII, whereas later non-phase-locked rhythms reflect stimulus-induced oscillations that are modulated by selective attention and may thus reflect enhanced processing of the stimulus underlying the perception of somatosensory events.

Mouse strain differences in opiate reward learning are explained by differences in anxiety, not reward or learning.

Gene-targeting techniques to produce null mutations provide a powerful method for evaluating the contribution of particular candidate genes involved in motivation. The embryonic stem cell lines in which homologous recombination is undertaken are derived from 129 mice, but because of the impoverished performance of 129 mice on a number of behavioral tasks, mice chimeric for the mutation are often bred with a C57BL/6 mouse strain. Thus, an examination of both parental strains is important in the study of the knock-out mice. Although the C57BL/6 behavioral phenotype is well documented, details of the 129 phenotype have not been the focus of study until recently. We investigated opiate motivation in both 129/SvJ and C57BL/6J mouse strains to determine whether, and under what circumstances, the 129/SvJ mouse exhibited motivated behavior toward opiates. 129/SvJ mice required both drug and contextual cues to demonstrate morphine conditioned place preferences on test day, whereas C57BL/6J mice required only contextual cues to express opiate place conditioning. Pentobarbital and diazepam but not saline, cocaine, or naloxone could substitute for morphine on test day in 129/SvJ mice, demonstrating that morphine indeed has rewarding motivational valence in the 129/SvJ mouse strain. This critical, interoceptive cue in 129/SvJ mice on test day may be the anxiolytic properties of the effective drugs. Therefore, some deficits observed in 129 mice and mice harboring this genetic background may be attributed to high levels of anxiety during the retrieval period rather than to sensory, learning, or motivational deficits.

The D2 receptor is critical in mediating opiate motivation only in opiate-dependent and withdrawn mice.

According to the dual systems model for opiate reward, dopamine mediates opiate motivation when an animal is in a deprived motivational state (i.e. opiate-dependent and in withdrawal) and not when an animal is in a nondeprived state (i.e. previously drug-naive). To determine the role of the D2 dopamine receptor subtype in mediating opiate motivation, we examined the behaviour of N5 congenic D2 receptor knockout mice and their wild-type siblings in opiate-naive and opiate-dependent and withdrawn place conditioning paradigms. Opiate-naive D2 receptor knockout mice demonstrated acquisition of morphine-conditioned place preference but failed to acquire place preference when conditioned in the deprived state. We propose that D2 receptor function is critical in mediating the motivational effects of opiates only when the animal is in an opiate-dependent and withdrawn motivational state. These findings also underscore the important influence of the genetic background to a given phenotype, as evidenced by the observation that increasing the allelic contribution from the 129/SvJ strain abolishes morphine place preference in C57BL/6 wild-type mice.