Paired-pulse Techniques Research Articles

Neurophysiological markers of motor compensatory mechanisms in early Parkinson's disease.

Compensatory mechanisms in Parkinson's disease are defined as the changes that the brain uses to adapt to neurodegeneration and progressive dopamine reduction. Motor compensation in early Parkinson's disease could, in part, be responsible for a unilateral onset of clinical motor signs despite the presence of bilateral nigrostriatal degeneration. Although several mechanisms have been proposed for compensatory adaptations in Parkinson's disease, the underlying pathophysiology is unclear. Here, we investigate motor compensation in Parkinson's disease by investigating the relationship between clinical signs, dopamine transporter imaging data and neurophysiological measures of the primary motor cortex (M1), using transcranial magnetic stimulation in presymptomatic and symptomatic hemispheres of patients. In this cross-sectional, multicentre study, we screened 82 individuals with Parkinson's disease. Patients were evaluated clinically in their medication OFF state using standardized scales. Sixteen Parkinson's disease patients with bilateral dopamine transporter deficit in the putamina but unilateral symptoms were included. Twenty-eight sex- and age-matched healthy controls were also investigated. In all participants, we tested cortical excitability using single- and paired-pulse techniques, interhemispheric inhibition and cortical plasticity with paired associative stimulation. Data were analysed with ANOVAs, multiple linear regression and logistic regression models. Individual coefficients of motor compensation were defined in patients based on clinical and imaging data, i.e. the motor compensation coefficient. The motor compensation coefficient includes an asymmetry score to balance motor and dopamine transporter data between the two hemispheres, in addition to a hemispheric ratio accounting for the relative mismatch between the magnitude of motor signs and dopaminergic deficit. In patients, corticospinal excitability and plasticity were higher in the presymptomatic compared with the symptomatic M1. Also, interhemispheric inhibition from the presymptomatic to the symptomatic M1 was reduced. Lower putamen binding was associated with higher plasticity and reduced interhemispheric inhibition in the presymptomatic hemisphere. The motor compensation coefficient distinguished the presymptomatic from the symptomatic hemisphere. Finally, in the presymptomatic hemisphere, a higher motor compensation coefficient was associated with lower corticospinal excitability and interhemispheric inhibition and with higher plasticity. In conclusion, the present study suggests that motor compensation involves M1-striatal networks and intercortical connections becoming more effective with progressive loss of dopaminergic terminals in the putamen. The balance between these motor networks seems to be driven by cortical plasticity.

Cortical excitability in human somatosensory and visual cortex: implications for plasticity and learning - a minireview.

The balance of excitation and inhibition plays a key role in plasticity and learning. A frequently used, reliable approach to assess intracortical inhibition relies on measuring paired-pulse behavior. Moreover, recent developments of magnetic resonance spectroscopy allows measuring GABA and glutamate concentrations. We give an overview about approaches employed to obtain information about excitatory states in human participants and discuss their putative relation. We summarize paired-pulse techniques and basic findings characterizing paired-pulse suppression in somatosensory (SI) and (VI) visual areas. Paired-pulse suppression describes the effect of paired sensory stimulation at short interstimulus intervals where the cortical response to the second stimulus is significantly suppressed. Simultaneous assessments of paired-pulse suppression in SI and VI indicated that cortical excitability is not a global phenomenon, but instead reflects the properties of local sensory processing. We review studies using non-invasive brain stimulation and perceptual learning experiments that assessed both perceptual changes and accompanying changes of cortical excitability in parallel. Independent of the nature of the excitation/inhibition marker used these data imply a close relationship between altered excitability and altered performance. These results suggest a framework where increased or decreased excitability is linked with improved or impaired perceptual performance. Recent findings have expanded the potential role of cortical excitability by demonstrating that inhibition markers such as GABA concentrations, paired-pulse suppression or alpha power predict to a substantial degree subsequent perceptual learning outcome. This opens the door for a targeted intervention where subsequent plasticity and learning processes are enhanced by altering prior baseline states of excitability.

P40-F The relationship between age and SICI parameters obtained with threshold tracking TMS

Background Recently developed threshold tracking TMS (TT-TMS) paired pulse techniques have been shown to be of benefit in clinical diagnostic practice. Reduced Short Interval Cortical Inhibition (SICI) with increasing age has been shown in several studies using conventional paired-pulse TMS techniques. However, TT-TMS SICI parameters did not correlate to age in healthy subjects in a previous study (Shibuya et al., 2016). We aimed in this study to present the preliminary results of our normal material on TT-SICI and the relationship between SICI measurements and age. Material and methods Thirty-three healthy subjects (mean age: 51.06 ± 2.48, range: 23–77) were included. Paired-pulse TT-TMS was undertaken using a 90 mm figure-of-eight coil applied to the motor cortex, with currents generated by BiStim system controlled by Qtrac software. The motor evoked potential (MEP) response was recorded over the first dorsal interosseus (FDI). MEP amplitude was set to a target value of 0.2 mV, and the changes in the intensity of the test stimulus required to generate this target MEP were measured. The relationship between age and SICI measurements were analyzed using regression analysis. Results Resting motor threshold (RMT) (MSO, %) (mean: 54.43 ± 2.41) and SICI (%) at 1 ms (12.01 ± 1.86), 2.5 ms (11.02 ± 1.65), 3 ms (8.20 ± 1.69) and 1–7 ms (5.93 ± 1.12) on TT-TMS were analysed. RMT increased with increasing age (r = 0.45, p = 0.08), while age had an inverse relationship with SICI on 1 ms (r = −0.49, p = 0.003), 2.5 ms (r = −0.45, p = 0.008), 3 ms (r = −0.41, p = 0.019) and 1–7 ms (r = −0.41, p = 0.017). Conclusions SICI parameters closely relate to age for TT-TMS similar to previously reported conventional. Further studies are required with large groups of healthy subjects.

Sensorimotor integration in chronic stroke: Baseline differences and response to sensory training.

The integration of somatosensory information from the environment into the motor cortex to inform movement is essential for motor function. As motor deficits commonly persist into the chronic phase of stroke recovery, it is important to understand potential contributing factors to these deficits, as well as their relationship with motor function. To date the impact of chronic stroke on sensorimotor integration has not been thoroughly investigated. The current study aimed to comprehensively examine the influence of chronic stroke on sensorimotor integration, and determine whether sensorimotor integration can be modified with an intervention. Further, it determined the relationship between neurophysiological measures of sensorimotor integration and motor deficits post-stroke. Fourteen individuals with chronic stroke and twelve older healthy controls participated. Motor impairment and function were quantified in individuals with chronic stroke. Baseline neurophysiology was assessed using nerve-based measures (short- and long-latency afferent inhibition, afferent facilitation) and vibration-based measures of sensorimotor integration, which paired vibration with single and paired-pulse TMS techniques. Neurophysiological assessment was performed before and after a vibration-based sensory training paradigm to assess changes within these circuits. Vibration-based, but not nerve-based measures of sensorimotor integration were different in individuals with chronic stroke, as compared to older healthy controls, suggesting that stroke differentially impacts integration of specific types of somatosensory information. Sensorimotor integration was behaviourally relevant in that it related to both motor function and impairment post-stroke. Finally, sensory training modulated sensorimotor integration in individuals with chronic stroke and controls. Sensorimotor integration is differentially impacted by chronic stroke based on the type of afferent feedback. However, both nerve-based and vibration-based measures relate to motor impairment and function in individuals with chronic stroke.

A Single Session of Repetitive Transcranial Magnetic Stimulation Over the Dorsolateral Prefrontal Cortex in Patients With Unresponsive Wakefulness Syndrome

Background. The level of consciousness is regulated by the activation of the frontal parietal network since a disruption within this interregional cortical connectivity is associated with a consciousness breakdown. Objective. The primary aim of the present study was to examine the feasibility and the safety of a single session of repetitive transcranial magnetic stimulation (rTMS), delivered over the dorsolateral prefrontal cortex (DLPFC), in patients with unresponsive wakefulness syndrome (UWS). As a secondary aim, we investigated the efficacy of rTMS over DLPFC on cortico-cortical connectivity as tested with paired-pulse and dual-coil TMS techniques. Methods. We enrolled 10 healthy and 10 postanoxic UWS subjects. After clinical assessment, subjects underwent a single/paired pulse TMS paradigm evaluating the inhibitory and facilitatory intracortical circuits. In addition, several interregional interactions between primary motor, dorsal and ventral premotor, supplementary motor, and posterior parietal cortex areas were investigated by means of dual-coil TMS technique. These parameters were evaluated at baseline, immediately after, and 60 minutes after a protocol of 10-Hz rTMS delivered at the level of the DLPFC. Results. rTMS over DLPFC did not cause any adverse events. We showed that rTMS over DLPFC did not induce, at group level, any clinical improvement or intra-/intercortical connectivity changes. Interestingly, in 3 patients rTMS induced a significant, although transient, clinical improvement associated with a short-lasting reshaping of brain connectivity. Conclusions. We demonstrated that a single session of 10-Hz rTMS over the right DLPFC may transiently improve consciousness and partially restore the connectivity within several cortical areas in some patients with UWS.

Early Visuomotor Integration Processes Induce LTP/LTD-Like Plasticity in the Human Motor Cortex

To investigate whether visuomotor integration processes induce long-term potentiation (LTP) and depression (LTD)-like plasticity in the primary motor cortex (M1), we designed a new paired associative stimulation (PAS) protocol coupling left primary visual area (V1) activation achieved by hemifield visual evoked potentials (VEPs) and transcranial magnetic stimulation (TMS) over the left M1, at specific interstimulus intervals (ISIs), delivered at 1 Hz (V-PAS). Before and after V-PAS, we measured motor evoked potentials (MEPs). To clarify the mechanisms underlying V-PAS, we tested the effect of 1-Hz repetitive TMS (rTMS), 0.25-Hz V-PAS and rTMS, and a shorter 0.25-Hz V-PAS protocol. To examine V-PAS with contralateral V1 activation, we delivered V-PAS activating the right V1. To clarify whether V-PAS increases V1 activity or parieto- and premotor-to-M1 connectivity, before and after V-PAS, we examined VEPs and MEPs evoked by paired-pulse techniques. V-PAS increased, decreased, or left MEPs unchanged according to the ISI used. After 1-Hz rTMS MEPs decreased. Although 0.25-Hz rTMS elicited no aftereffect, 0.25-Hz V-PAS modulated MEPs according to the ISI used. The short 0.25-Hz V-PAS protocol left MEPs unchanged. Contralateral V-PAS inhibited MEPs. After V-PAS, VEPs remained unchanged and the premotor-to-M1 inhibitory connections decreased. V-PAS induces M1 LTP/LTD-like plasticity by activating premotor-to-motor connections.

Effects of Night Sleep on Motor Learning Using Transcranial Magnetic Stimulation

ObjectiveTo investigate the effects of night sleep on motor cortical excitability with TMS (transcranial magnetic stimulation) and finger tapping performance.MethodEight volunteers were enrolled to investigate the effects of day wake or night sleep on motor learning and finger performance. Each subject underwent a finger tapping task over a 12 hour period, which was employed to evaluate the motor cortical excitability affected by motor learning. Starting at 9:00 am for the day wake cycle and restarting at 9:00 pm for the night sleep cycle. The finger tapping task was the index finger of the non-dominant hand with the Hangul word personal computer (PC) training program. The data was assessed by comparing the changes observed with the cortical excitability and finger tapping performance tests between the day wake and night sleep after equivalent amounts of training.ResultsThe results showed that in paired-pulse techniques, there was a significant decrease of intracortical inhibition (ICI) in the morning following the night sleep cycle (p<0.05), but no significant change was seen in the ICI in the evening for the day wake cycle. In addition a significant decrease of the ICI was observed in comparison to the morning following the night sleep cycle and the evening following the day wake cycle (p<0.05). The 140% recruitment curve (RC) and accuracy of the finger tapping performance demonstrated a significant improvement for both cycles (p<0.05).ConclusionThrough this study, we observed that the Hangul typing practice requires both explicit and implicit skill learning. And also the off-line learning during a night of sleep may be affected by an inhibitory neurotransmitter related synaptic plasticity and by the time dependent learning with recruitments of remote or less excitable motor neurons in the primary motor cortex.

Understanding the mechanisms of neuromuscular fatigue with paired‐pulse stimulation

Transcranial magnetic stimulation (TMS), using both single and paired-pulse techniques, has provided insight in understanding the balance of excitation and inhibition within the corticomotor system during maximal and submaximal exercise. A single pulse of TMS produces a short-latency motor-evoked potential (MEP), indicating the net excitation of the motor pathway which includes the balance within supraspinal (cortical) and spinal sources. The MEP is followed by an interruption of ongoing electromyographic (EMG) activity known as the silent period. Classically, the silent period has been interpreted to represent the inhibition within the motor cortex (i.e. intracortical inhibition) which probably involves γ-aminobutyric acid (GABAB) receptors. Intracortical inhibition is clinically important to understand because chronic pain disorders (migraines) and psychiatric disorders (post-traumatic stress disorder) have demonstrated less cortical inhibition during a voluntary contraction while other disorders such as Parkinson's and Alzheimer's diseases have demonstrated abnormal corticospinal excitatory circuits at rest. Additionally, the fatigue-induced reduction in cortical inhibition may be related to the motor impairments during exercise. The alterations in the MEP and silent period during exercise indicate that the central nervous system (CNS) may necessitate increases in both excitatory and inhibitory activity during fatiguing contractions; however, the mechanisms underlying these effects are yet to be completely understood.

Multichannel SEP-recording after paired median nerve stimulation suggests origin of paired-pulse inhibition rostral of the brainstem

Paired-pulse techniques are a common tool to investigate the excitability of the cerebral cortex. Whereas in the motor system short interval intracortical inhibition assessed by paired-pulse transcranial magnetic stimulation clearly could be demonstrated to be generated within the motor cortex, the mechanism of paired-pulse inhibition measured over the somatosensory cortex after paired-pulse median nerve stimulation is less clear. The aim of this study was to further investigate the level of somatosensory processing where this paired-pulse inhibition is generated. We applied single and paired electrical stimulation of the median nerve with an interstimulus interval of 30 ms. Somatosensory evoked potentials were recorded over the brachial plexus, the cranial cervical medulla and the primary somatosensory cortex. We analyzed peak-to-peak amplitudes evoked by the second stimulus of paired-pulse stimulation after digital subtraction of a single pulse (A2s), and referred it to the first response before linear subtraction (A1). Paired-pulse inhibition was expressed as a ratio (A2s/A1) of the amplitudes of the second (A2s) and the first (A1) peaks. We found a significant reduction of A2s as compared to A1 over S1, but no significant difference between A1 and A2s over brachial plexus and cranial medulla. In addition, the cortical amplitude ratio A2s/A1 was significantly reduced compared to the amplitude ratios over cranial medulla and brachial plexus. These results suggest that the underlying inhibitory mechanisms are generated rostral to the brainstem nuclei, probably due to the activity of thalamic or intracortical inhibitory interneurons.

Synaptic strength and postsynaptically silent synapses through advanced aging in rat hippocampal CA1 pyramidal neurons

Synaptic dysfunction is thought to contribute to age-related learning impairments. Detailed information regarding the presence of silent synapses and the strength of functional ones through advanced aging, however, is lacking. Here we used paired-pulse minimal stimulation techniques in CA1 stratum radiatum to determine whether the amplitude of spontaneous and evoked miniature excitatory postsynaptic currents (sEPSCs and eEPSCs, respectively) changes over the lifespan of rats in hippocampal CA1 pyramidal neurons, and whether silent synapses are present in adult and aged rats. The amplitudes of both sEPSCs and eEPSCs at resting membrane potential (i.e., clamped at −65mV) initially increased between 2 weeks and 3 months, but then remained constant through 36 months of age. The potency of the eEPSCs at depolarized membrane potentials (i.e., clamped at +40mV), however, was highest among 36-month old rats. Additionally, presynaptically silent synapses in CA1 stratum radiatum disappeared between 2 weeks and 3 months, but postsynaptically silent synapses were present through advanced aging. The similarity of silent and functional synapses in CA1 hippocampus at resting membrane potentials throughout adulthood in rats may indicate that impairments in the mechanisms of synaptic plasticity and its subsequent stabilization, rather than deficient synaptic transmission, underlie age-related cognitive decline. Such a notion is consistent with the increased amplitude of synaptic currents at depolarized potentials, perhaps suggesting an upregulation in the expression of synaptic NMDA receptors once rats reach advanced age.

Sustained increase of somatosensory cortex excitability by tactile coactivation studied by paired median nerve stimulation in humans correlates with perceptual gain

Cortical excitability can be reliably assessed by means of paired-pulse stimulation techniques. Recent studies demonstrated particularly for motor and visual cortex that cortical excitability is systematically altered following the induction of learning processes or during the development of pathological symptoms. A recent tactile coactivation protocol developed by Godde and coworkers showed that improvement of tactile performance in humans can be achieved also without training through passive stimulation on a time scale of a few hours. Tactile coactivation evokes plastic changes in somatosensory cortical areas as measured by blood oxygenation level-dependent (BOLD) activation in fMRI or SEP-dipole localization, which correlated with the individual gain in performance. To demonstrate changes in excitability of somatosensory cortex after tactile coactivation, we combined assessment of tactile performance with recordings of paired-pulse SEPs after electrical median nerve stimulation of both the right coactivated and left control hand at ISIs of 30 and 100 ms before, 3 h after and 24 h after tactile coactivation. Amplitudes and latencies of the first and second cortical N20/P25 response components were calculated. For the coactivated hand, we found significantly lowered discrimination thresholds and significantly reduced paired-pulse ratios (second N20/P25 response/first N20/P25 response) at an ISI of 30 ms after tactile coactivation indicating enhanced cortical excitability. No changes in paired-pulse behaviour were observed for ISIs of 100 ms. Both psychophysical and cortical effects recovered to baseline 24 h after tactile coactivation. The individual increase of excitability correlated with the individual gain in discrimination performance. For the left control hand we found no effects of tactile coactivation on paired-pulse behaviour and discrimination threshold. Our results indicate that changes in cortical excitability are modified by tactile coactivation and were scaled with the degree of improvement of the individual perceptual learning. Conceivably, changes of cortical excitability seem to constitute an additional important marker and mechanism underlying plastic reorganization.

Improvement of motor performance and modulation of cortical excitability by repetitive transcranial magnetic stimulation of the motor cortex in Parkinson's disease

Objective: To assess the effects of focal motor cortex stimulation on motor performance and cortical excitability in patients with Parkinson's disease (PD). Methods: Repetitive transcranial magnetic stimulation (rTMS) was performed on the left motor cortical area corresponding to the right hand in 12 ‘off-drug’ patients with PD. The effects of subthreshold rTMS applied at 0.5 Hz (600 pulses) or at 10 Hz (2000 pulses) using a ‘real’ or a ‘sham’ coil were compared to those obtained by a single dose of l-dopa. The assessment included a clinical evaluation by the Unified Parkinson's Disease Rating Scale and timed motor tasks, and a neurophysiological evaluation of cortical excitability by single- and paired-pulse TMS techniques. Results: ‘Real’ rTMS at 10 or 0.5 Hz, but not ‘sham’ stimulation, improved motor performance. High-frequency rTMS decreased rigidity and bradykinesia in the upper limb contralateral to the stimulation, while low-frequency rTMS reduced upper limb rigidity bilaterally and improved walking. Concomitantly, 10 Hz rTMS increased intracortical facilitation, while 0.5 Hz rTMS restored intracortical inhibition. Conclusions: Low- and high-frequency rTMS of the primary motor cortex lead to significant but differential changes in patients with PD both on clinical and electrophysiological grounds. The effects on cortical excitability were opposite to previous observations made in healthy subjects, suggesting a reversed balance of cortical excitability in patients with PD compared to normals. However, the underlying mechanisms of these changes remain to determine, as well as the relationship with clinical presentation and response to l-dopa therapy. Significance: The present study gives some clues to appraise the role of the primary motor cortex in PD. Clinical improvement induced by rTMS was too short-lasting to consider therapeutic application, but these results support the perspective of the primary motor cortex as a possible target for neuromodulation in PD.

Transcranial Magnetic Stimulation in Epilepsy.

Transcranial magnetic stimulation (TMS) seems an attractive tool for the study of seizure disorders. It is simple to perform, relatively inexpensive, and generally safe, with the potential to provide noninvasive clinical measurements of neuronal excitability. Applications in patients with epilepsy include investigation of underlying cortical excitability and determination of the effects of antiepileptic drugs (AEDs); preoperative localization of epileptic foci; and functional mapping. Several review articles have been published on the use of TMS for epilepsy (1, 2, 3, 4, 5). Most intriguingly, TMS could become a new seizure treatment modality. The parameters measured by TMS include motor threshold, which is the minimal threshold for motor response in target muscle and motor evoked potential (MEP) amplitude, both measured using single pulses (see Table 1). The cortical silent period (CSP) is a lapse in electromyogram (EMG), when a TMS pulse is given during tonic voluntary muscle contraction; its duration is related to stimulus intensity. Additional parameters are measured with paired-pulse stimulation techniques. For example, intracortical inhibition (ICI), a decrease in MEP amplitude from the first to the second stimulus, is seen when a subthreshold conditioning pulse is followed by a suprathreshold pulse after a 2- to 5-millisecond delay, whereas intracortical facilitation (ICF) occurs when the pulses are 7 to 20 milliseconds apart. TABLE 1 TMS Parameters

Changes in nonlinear signal processing in rat hippocampus associated with loss of paired-pulse inhibition or epileptogenesis.

To study acute and chronic physiological effects of perforant path stimulation using paired-pulse and nonlinear signal analysis techniques (Wiener kernel analysis). Two to 3-month-old Wistar rats were implanted with stimulating electrodes in the perforant path and recording electrodes in the granule cell layer. Loss of paired-pulse inhibition was produced with 2 Hz continuous and 20 Hz (10 s/min) intermittent stimulation for periods of 1-15 min (0.1 ms, 20 v pulses). Some animals received 30-60 min of stimulation, a model for status epilepticus/epileptogenesis. Responses to paired-pulse or white noise inputs were recorded sequentially. Loss of inhibition with brief 1-3 min of stimulation, measured by increase paired-pulse ratio (P2/P1 ISI 40 ms) from 0.25 (+/-0.27) pre- to 1.02 (+/-0.18) post-stimulation (p < 0.001), lasted 43 (+/-15) min. For 30-60 min of stimulation, the paired-pulse ratios were 0.088 (+/-0.11), 1.59 (+/-0.036), 0.06 (+/-0.11), 0.82 (+/-0.22) for pre-, immediate post-, 1 week post-, and 1 month poststimulation, respectively (p < 0.025). Compared to prestimulation values, Wiener kernel amplitudes for immediate, 1 week, and 1 month poststimulation were 24% (+/-13%), 72% (+/-17%), and 31% (+/-21%), respectively (p < 0.05). Wiener kernels 1 month poststimulation showed response prolongation with increased opportunity for excitatory interactions of inputs (particularly those separated by 4 ms). Brief perforant path stimulation causes sustained loss of inhibition in the dentate, possibly an early event in the transition to status epilepticus. Stimulation for 30-60 min causes chronic changes in paired-pulse and white noise (Wiener kernel) responses. Transient recovery occurs by 1 week, but later new features appear (including delayed/late inhibition and potential excitatory cross-talk) that might favor epileptic seizures.

Transcranial magnetic stimulation and neuroplasticity

We review past results and present novel data to illustrate different ways in which TMS can be used to study neural plasticity. Procedural learning during the serial reaction time task (SRTT) is used as a model of neural plasticity to illustrate the applications of TMS. These different applications of TMS represent principles of use that we believe are applicable to studies of cognitive neuroscience in general and exemplify the great potential of TMS in the study of brain and behavior. We review the use of TMS for (1) cortical output mapping using focal, single-pulse TMS; (2) identification of the mechanisms underlying neuroplasticity using paired-pulse TMS techniques; (3) enhancement of the information of other neuroimaging techniques by transient disruption of cortical function using repetitive TMS; and finally (4) modulation of cortical function with repetitive TMS to influence behavior and guide plasticity.

Modulation of the synaptic drive to respiratory premotor and motor neurons

The characteristics of GABAergic inhibitory modulation of respiratory bulbospinal neuronal activity and short-term potentiation (STP) of phrenic motoneuronal activity were studied. Extracellular unit recording and picoejection techniques in anesthetized dogs showed that both the spontaneous rhythmic and reflexly induced discharge patterns of inspiratory (I) and expiratory (E) premotor neurons were proportionately amplified by the localized application of picomole amounts of bicuculline (Bic), a competitive GABA A antagonist. Intracellular recording and paired-pulse stimulation techniques in anesthetized rats demonstrated an STP of phrenic motor output that appears to be mediated by NMDA receptors and is associated with facilitation of EPSPs and prolonged depolarization of individual phrenic motoneurons. We speculate that both GABAergic gain modulation of premotor neuronal activity and NMDA-mediated STP of phrenic activity may be neural substrates which are involved with the optimization of respiratory and non-respiratory behaviors, via adaptive and/or differential control of breathing.

Chronic ethanol treatment reduces inhibition in CA1 of the rat hippocampus

The effect of chronic ethanol exposure on inhibition in the rat hippocampal slice was investigated using paired-pulse stimulation techniques with stimulation in stratum radiatum or stratum oriens of CA1. Experimental animals were fed ethanol in a liquid diet for 20 weeks and were withdrawn for at least 8 weeks prior to electrophysiological recording. Prior ethanol treatment had no effect on basic input-output relationships for the extracellular population spike. Ethanol treatment significantly reduced the recurrent inhibition produced by antidromic stimulation in a manner dependent upon stimulus intensity. In addition, with orthodromic paired-pulse stimulation of either stratum radiatum or oriens, a trend toward an augmentation of the facilitation of population spike amplitude was observed, suggesting that feedforward inhibition may also be reduced. These results are similar to those found with treatments that reduce inhibition. Therefore, we conclude that chronic ethanol exposure produces an enduring disruption of inhibitory neuronal function in the rat hippocampus.

Quantitative measurement of neural post-stimulation excitability with behavioral methods

Previous paired-pulse techniques for estimating neural refractory periods of neurons mediating behaviors elicited by electrical stimulation of the brain are shown to be inadequate for characterizing the distribution of refractory periods. A new method is proposed which makes possible quantitative analysis of neural excitability cycle changes. Excitability increases for fibers mediating bar pressing for rewarding brain stimulation are found at all C-T intervals from 0.4 to 1.2 msec. The results are discussed in terms of local potential summation, relative and absolute refractory periods.