Sensory effects of baroreceptor activation and perceived stress together predict long-term blood pressure elevations

Activating the arterial baroreceptors in animals has been shown to blunt pain sensation and provide other forms of central nervous system inhibition. This study tested the hypothesis that, among human subjects, a tonic increase in blood pressure (BP) could be a learned response to environmental stressors among subjects in whom the baroreceptor inhibitory mechanism is active. In a sample of 96 healthy, normotensive men and women, amount of pain-reduction produced by baroreceptor stimulation predicted an increase in resting BP 20 months later: the increase was proportional to self-assessed daily life stress. Among the subjects reporting the greatest amount of stress, the pain inhibition effect accounted for more than 80% of the BP variance. These results support the hypothesis that the reduction in perceived stress produced by baroreceptor stimulation may reward learned increases in BP. This research was supported by Deutsche Forschungsgemeinshaft Grant EL 101/3 to Thomas Elbert and National Institutes of Health Grant ROl HL40837 to B. R, Dworkin.     

Loss of tolerance to morphine after a change in route of administration: control of within-session tolerance by interoceptive conditioned stimuli

Tolerance to morphine analgesia (tail-immersion test) was examined after manipulation of two aspects of a tolerance test: 1) the route of drug administration and 2) the time interval between the test dosing and the tolerance test. The intravenous (IV) and intraperitoneal (IP) routes were used, together with a novel test for tolerance in which the test morphine was infused IV just 2 min before measuring the opiate effect. The first experiment validated this test as an assay for tolerance by examining the log dose-response (LDR) curve changes produced by daily IP injection with 0, 20 or 200 mg/kg morphine; the IV test confirmed the expected parallel shift to the right and flattening of the LDR curve. In the second experiment, all rats of two groups were injected once daily for 3 weeks with 20 mg/kg morphine and with saline except that one group received the morphine IV (and saline IP), the other morphine IP (saline IV). The results indicated route-specific tolerance. On a test using 20 mg/kg given IV morphine, tolerance was significantly greater in rats treated with IV morphine than in those treated IP. However, a larger effect on tolerance was produced by a pretest application of 5 mg/kg morphine 30 min before the actual tolerance test. This manipulation was designed to prime short-term, adaptive processes hypothesized to occur within a normal tolerance test session as morphine is taking effect. The tolerance on the test increased (equivalent to 2 to 3 fold shift in the LDR curve) when the pretest morphine was given with the same route as the chronic morphine, regardless of treatment group. It was concluded that opiate tolerance may be modulated by conditioned stimuli produced by morphine acting through different routes. These interoceptive cues appear to modulate rapidly acquired and short-lived adaptive processes taking place within a given test session.     

Right-hemisphere dominance for the processing of sound-source lateralization.

Cortical processing of change in direction of a perceived sound source was investigated in 12 human subjects using whole-head magnetoencephalography. The German word "da" was presented either with or without 0.7 msec interaural time delays to create the impression of right- or left-lateralized or midline sources, respectively. Midline stimuli served as standards, and lateralized stimuli served as deviants in a mismatch paradigm. Two symmetrically linked dipoles fitted to the mismatch fields showed stronger moments in the hemisphere contralateral to the side of the deviant. The right dipole displayed equal latencies to both left and right deviants, whereas left dipole latencies were longer for ipsilateral than contralateral deviants. Frequency analysis between 20-70 Hz and statistical probability mapping revealed increased induced gamma-band activity at 53+/-2.5 Hz to both types of deviants. Right deviants elicited spectral amplitude enhancements in this frequency range, peaking at latencies of 160 and 240 msec. These effects were localized bilaterally over the angular gyri and posterior temporal regions. Coherence analysis suggested the existence of two separate interhemispheric networks. For left-lateralized deviants, both spectral amplitude enhancements at 110 and 220 msec and coherence increases were restricted to the right hemisphere. In conclusion, both mismatch dipole latencies at the supratemporal plane and gamma-band activity in posterior parietotemporal areas suggested a right hemisphere engagement in the processing of bidirectional sound-source shifts. In contrast, left-hemisphere regions responded predominantly to contralateral events. These findings may help to elucidate phenomena such as unilateral auditory neglect.     

Why Do Patients with Partial Epilepsy Improve Their IQ After Training to Self-Regulate Slow Cortical Potentials?

In patients with epilepsy, not only seizures but also cognitive, emotional, and social functioning are of increasing interest in research (Kelley, Jacobs, &; Lowenstein, 2009 Kelley , M. S. , Jacobs , M. P. , &; Lowenstein , D. H. , for the NINDS Epilepsy Benchmark Stewards . ( 2009 ). The NINDS epilepsy research benchmarks . Epilepsia , 50 , 579 – 582 . doi: doi:10.1111/j.1528-1167.2008.01813.x  [Google Scholar]). As a decrease in cognitive functions over the course of the illness is usually reported, we wanted to explore changes in Intelligence Scores observed after a neurofeedback treatment in patients with drug-resistant epilepsies. In a controlled study that compared the outcome of three different interventions (training to regulate slow cortical potentials, N = 34; training to regulate breath rate and the amount of carbon dioxide in the end tidal volume of the exhaled air, N = 11; modification of drug regime, N = 25), pre- and postmeasurements of a short version of the Wechsler Intelligence Scale were applied. The interval between the two assessments was more than 12 months, with a mean of 61 weeks. Mean age of the patients was 35, with a range from 17 to 57. The highly significant 7-point increment of IQ only after training of slow cortical potentials was not related to clinical (e.g., seizure reduction) or neuropsychological (e.g., attention and memory) variables. Instead, it was related to psychophysiological measures: IQ change was inversely related to the Latency of the P300 component of event-related brain potentials and directly related to the Latency of the P2 component and the increase of N2 Amplitude during training. We conclude that regulation training of slow cortical potentials improves IQ in patients with refractory partial epilepsy, which might be related to an improved ability for controlled allocation of cognitive resources.     

Acquired self‐control of insula cortex modulates emotion recognition and brain network connectivity in schizophrenia

Real‐time functional magnetic resonance imaging (rtfMRI) is a novel technique that has allowed subjects to achieve self‐regulation of circumscribed brain regions. Despite its anticipated therapeutic benefits, there is no report on successful application of this technique in psychiatric populations. The objectives of the present study were to train schizophrenia patients to achieve volitional control of bilateral anterior insula cortex on multiple days, and to explore the effect of learned self‐regulation on face emotion recognition (an extensively studied deficit in schizophrenia) and on brain network connectivity. Nine patients with schizophrenia were trained to regulate the hemodynamic response in bilateral anterior insula with contingent rtfMRI neurofeedback, through a 2‐weeks training. At the end of the training stage, patients performed a face emotion recognition task to explore behavioral effects of learned self‐regulation. A learning effect in self‐regulation was found for bilateral anterior insula, which persisted through the training. Following successful self‐regulation, patients recognized disgust faces more accurately and happy faces less accurately. Improvements in disgust recognition were correlated with levels of self‐activation of right insula. RtfMRI training led to an increase in the number of the incoming and outgoing effective connections of the anterior insula. This study shows for the first time that patients with schizophrenia can learn volitional brain regulation by rtfMRI feedback training leading to changes in the perception of emotions and modulations of the brain network connectivity. These findings open the door for further studies of rtfMRI in severely ill psychiatric populations, and possible therapeutic applications. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Brain oscillatory activity as a biomarker of motor recovery in chronic stroke

In the present work, we investigated the relationship of oscillatory sensorimotor brain activity to motor recovery. The neurophysiological data of 30 chronic stroke patients with severe upper‐limb paralysis are the basis of the observational study presented here. These patients underwent an intervention including movement training based on combined brain–machine interfaces and physiotherapy of several weeks recorded in a double‐blinded randomized clinical trial. We analyzed the alpha oscillations over the motor cortex of 22 of these patients employing multilevel linear predictive modeling. We identified a significant correlation between the evolution of the alpha desynchronization during rehabilitative intervention and clinical improvement. Moreover, we observed that the initial alpha desynchronization conditions its modulation during intervention: Patients showing a strong alpha desynchronization at the beginning of the training improved if they increased their alpha desynchronization. Patients showing a small alpha desynchronization at initial training stages improved if they decreased it further on both hemispheres. In all patients, a progressive shift of desynchronization toward the ipsilesional hemisphere correlates significantly with clinical improvement regardless of lesion location. The results indicate that initial alpha desynchronization might be key for stratification of patients undergoing BMI interventions and that its interhemispheric balance plays an important role in motor recovery.     

Magnetic oscillatory responses to lateralization changes of natural and artificial sounds in humans

Oscillatory signals in human magnetoencephalogram were investigated as correlates of cortical network activity in response to sound lateralization changes. Previously, we found lateralized presentations of a monosyllabic word to elicit posterior temporo-parietal gamma-band activity, possibly reflecting synchronization of neuronal assemblies in putative auditory dorsal stream areas. In addition, beta activity was decreased over sensorimotor regions, suggesting the activation of motor networks involved in orientating. The present study investigated responses to lateralization changes of both a barking dog sound and a distorted noise to test whether beta desynchronization would depend on the sound's relevance for orientating. Eighteen adults listened passively to 900 samples of each sound in separate location mismatch paradigms with midline standards and both right- and left-lateralized deviants. Lateralized distorted noises were accompanied by enhanced spectral amplitude at 58-73 Hz over right temporo-parietal cortex. Left-lateralized barking dog sounds elicited right and right-lateralized sounds elicited bilateral temporo-parietal spectral amplitude increases at approximately 77 Hz. This replicated the involvement of posterior temporo-parietal areas in auditory spatial processing. Only barking dog sounds, but not distorted noises, gave rise to 30 Hz desynchronization over contralateral sensorimotor areas, parieto-frontal gamma coherence increases and beta coherence reductions between sensorimotor and prefrontal sensors. Apparently passive listening to lateralized natural sounds with a potential biological relevance led to an activation of motor networks involved in the automatic preparation for orientating. Parieto-frontal coherence increases may reflect enhanced coupling of networks involved in the integration of auditory spatial and motor processes.     

Effects of water on cortical excitability in humans

The effects of water on cortical excitability, measured using magnetoencephalographic recordings, were investigated in a sample of 19 healthy volunteers in a double-blind, placebo experiment comparing water with saline solution. Spontaneous magnetoencephalogram as well as auditory-evoked magnetic fields were recorded before and after the drinking of 750 mL water (9 subjects) or saline solution (10 subjects) and during and after hyperventilation following the drinking conditions. Hyperventilation was used to enhance the hypothesized synchronizing effect of water on spontaneous magnetoencephalographic activity. In addition, the magnetic fields were measured during a dichotic listening task under attended and unattended conditions. The prediction, that intake of water, because of induced cell swelling, will increase neuronal excitability and lead to an increased synchronization of the spontaneous magnetoencephalogram during hyperventilation was confirmed. Hyperventilation induced an increase of spectral power in all frequency bands particularly theta and delta power after water drinking. Furthermore, there was an increase of magnetic mismatch negativity (MMNm) amplitude in attended conditions and a simultaneous decrease in unattended conditions after water drinking. N1m (magnetic N1 wave) revealed significant changes during experimental conditions: increase after drinking and decrease after hyperventilation in both groups. MMNm for attended conditions showed a high positive correlation with osmolality changes (difference in the mol solute per kg water before and after drinking); N1m and PNm (magnetic processing negativity) as well as MMNm for unattended conditions showed significant correlations with subjective ratings of thirst and mood state.     

Phantom limb pain: cortical plasticity and novel therapeutic approaches

Phantom limb pain is still a very frequent consequence of peripheral deafferentation or amputation of a limb. Recent findings from animal and neuroimaging studies suggest that phantom limb pain might be a central phenomenon, related to changes in the cortical, thalamic and spinal representation of the painful limb, and might be a type of somatosensory pain memory. Based on these assumptions, new treatment approaches focus on sensory discrimination training or motor cortex stimulation in an effort to influence cortical reorganization. Prevention of perpetuation of a somatosensory pain memory might also be possible through pharmacological agents such as N-methyl-D-aspartate antagonists and gamma-aminobutyric acid agonists, substances that have been shown to influence and prevent cortical reorganization.     

Sequence analysis of restricted associative response in aphasia

A sequence analysis of restricted associative responses (animals, food and things to be seen on the street) was done for 50 aphasic and 50 control Ss. The two groups were equated with respect to age, sex and educational level. In aphasics the number of given associations diminuishes approximately in direct proportion to the elapsed time, whilst in normal controls the decrease of associations is dependent on the square-root of time; the starting-level of the aphasics is lower. The results suggest both a qualitative and a quantitative change in the mechanism producing associations in aphasia.