Hillel Pratt

Auditory brain stem evoked potentials: clinical promise of increasing stimulus rate.

Auditory brain stem evoked potentials (ABEPs) were recorded from 10 adults and 10 children who where neurologically and audiometrically normal. ABEPs were recorded in response to 75 dB HL clicks presented at rates of 10/sec and 50/sec. Normative values were calculated for amplitude and latency, as well as for inter-peak amplitude ratio and a variety of inter-peak latency differences and interaural differences at the two stimulus presentation rates. Normative values of the effect of increasing stimulus rate were calculated as well. Measures of changes in ABEPs between stimulus rates of 50/sec and 10/sec were the only derived measures that were significantly different between our adult and child normal populations. In addition, 50 patients with various conditions affecting the brain stem were examined. Increasing stimulus presentation rate had a significant effect on detection of abnormality in ABEPs from the patients examined. Measures of changes in ABEPs between stimulus rates of 50/sec and 10/sec seemed to be sensitive to a subset of abnormalities in our patient population. The case histories of the patients indicate that the subset may be impaired synaptic function. Measures of the effect of rate on ABEPs may complement the traditional measures that are primarily sensitive to white matter lesions.

Artifact correction and source analysis of early electroencephalographic responses evoked by transcranial magnetic stimulation over primary motor cortex.

Analyzing the brain responses to transcranial magnetic stimulation (TMS) using electroencephalography (EEG) is a promising method for the assessment of functional cortical connectivity and excitability of areas accessible to this stimulation. However, until now it has been difficult to analyze the EEG responses during the several tens of milliseconds immediately following the stimulus due to TMS-induced artifacts. In the present study we show that by combining a specially adapted recording system with software artifact correction it is possible to remove a major part of the artifact and analyze the cortical responses as early as 10 ms after TMS. We used this methodology to examine responses of left and right primary motor cortex (M1) to TMS at different intensities. Based on the artifact-corrected data we propose a model for the cortical activation following M1 stimulation. The model revealed the same basic response sequence for both hemispheres. A large part of the response could be accounted for by two sources: a source close to the stimulation site (peaking approximately 15 ms after the stimulus) and a midline frontal source ipsilateral to the stimulus (peaking approximately 25 ms). In addition the model suggests responses in ipsilateral temporo-parietal junction areas (approximately 35 ms) and ipsilateral (approximately 30 ms) and middle (approximately 50 ms) cerebellum. Statistical analysis revealed significant dependence on stimulation intensity for the ipsilateral midline frontal source. The methodology developed in the present study paves the way for the detailed study of early responses to TMS in a wide variety of brain areas.

Modeling and estimation of single evoked brain potential components

Presents a novel approach to solving the single-trial evoked-potential estimation problem. Recognizing that different components of an evoked potential complex may originate from different functional brain sites and can be distinguished according to their respective latencies and amplitudes, the authors propose an estimation approach based on identification of evoked potential components on a single-trial basis. The estimation process is performed in 2 stages: first, an average evoked potential is calculated and decomposed into a set of components, with each component serving as a subtemplate for the next stage; then, the single measurement is parametrically modeled by a superposition of an emulated ongoing electroencephalographic activity and a linear combination of latency and amplitude-corrected component templates. Once optimized, the model provides the 2 assumed signal contributions, namely the ongoing brain activity and the single evoked brain response. The estimators performance is analyzed analytically and via simulation, verifying its capability to extract single components at low signal-to-noise ratios typical of evoked potential data. Finally, 2 applications are presented, demonstrating the improved analysis capabilities gained by using the proposed approach. The first application deals with movement related brain potentials, where a change of the single evoked response due to external loading is detected. The second application involves cognitive event-related brain potentials, where a dynamic change of 2 overlapping components throughout the experimental session is detected and tracked.

Mechanically and electrically evoked somatosensory potentials in humans: Effects of stimulus presentation rate

Somatosensory evoked potentials were recorded in response to: (1) electrical stimulation of the median nerve at the wrist; (2) electrical stimulation of the index finger; (3) mechanical stimulation of the index fingernail. Stimuli were presented at rates of 2, 4, 8, 16 and 32/sec, and the effects of presentation rate on components of the evoked potentials were evaluated. The effect of varying the duration of the mechanical stimulus was also observed. The findings suggest that stimulus rates of up to 8/sec can be used without significant loss in detectability of most of the components. The potentials recorded in response to a short duration mechanical stimulus were essentially identical to those evoked by the long duration stimulus. The findings of this study are consistent with a peripheral nerve generator for the Erbs point recorded component, a postsynaptic generator for the upper neck recorded component, and in general with a larger number of synapses leading to the generators of the later components than to earlier ones.

`Oddball' event-related potentials and information processing during REM and non-REM sleep

Auditory stimuli consisting of the subjects own name and an irrelevant word, counterbalanced in probabilities, were presented to 15 male subjects in the awake state and during natural sleep. Potentials recorded to these stimuli, as well as to clicks presented during sleep in a preceding night, were recorded and compared. Principal component analysis (PCA) was conducted on evoked potentials to distinguish temporally overlapping components, and ANOVA was applied on the eigenvector coefficients. During non-REM sleep a parietal P450, more prominent in stage 2, was observed in addition to the prominent waveform of a K-complex, which was also recorded in response to clicks and consisted of N350, N550 and P1000. During REM sleep, a fronto-central negativity which resembled non-REM N350, a parietal positivity at about 450 ms and a large N700 were detected. ANOVA on PCA coefficients showed a significant effect of verbal-stimulus type (name/irrelevant) on an eigenvector, which included all the components observed during stage 2 sleep. Coefficients during REM sleep showed a significant effect of stimulus probability on an eigenvector consisting of a prominent P450, suggesting a resemblance to the awake P300 component. This could not be demonstrated during non-REM sleep. The results indicate continued evaluation of auditory input salience during sleep, which diminishes during deep sleep, and is replaced by evaluation of stimulus context in a train of stimuli during REM sleep.

Cisplatin ototoxicity in guinea pigs with special reference to toxic effects in the stria vascularis

The toxic effects of cisplatin (cis‐diamminedichloroplatinum [II]) on the organ of Corti are well established. Few and conflicting data on this drugs effects on the stria vascularis exist. The present study presents animal experiments on the toxic effects of cisplatin in the stria vascularis and in the organ of Corti. Cisplatin‐induced toxicity in albino and pigmented guinea pigs was evaluated morphologically and functionally, using light and transmission electron microscopy as well as auditory brainstem‐evoked potentials on the organ of Corti and the stria vascularis. The results showed variability in hearing thresholds, ranging from no change to hearing loss of 30 dB, and prominent damage in the organ of Corti and in the stria vascularis. The toxic effects to both the organ of Corti and the stria vascularis should be considered when cisplatin is used in chemotherapy.

Auditory brain-stem evoked potentials to clicks at different presentation rates: estimating maturation of pre-term and full-term neonates.

Auditory brain-stem evoked potentials ABEPs were recorded from 57 neonates ranging in gestational age between 27 and 43 weeks. Averages and standard deviations of I, III and V peak latencies, I-V, I-III and III-V inter-peak latency differences (IPLDs), for 10/sec and 55/sec clicks were calculated for each age group. An additional measure, the net effect of increasing stimulus rate (ISR), was calculated by subtracting 10/sec measures from their 55/sec counterparts. Correlations between ABEP measures and subject age were determined. The results of this study demonstrate a significant correlation between gestational age and electrophysiological measures of peripheral, as well as central, conduction: an inverse correlation between age and peak latencies as well as IPLDs. The slope of this correlation was steeper for the higher stimulus rate. The slope of 55/sec measures vs. age was the sum of the respective slopes of 10/sec measures and of ISR. The maturation of 10/sec measures may reflect white matter development, while ISR changes with gestational age represent maturation of synaptic efficacy. Thus, the maturation of 55/sec measures reflect the combined maturation of nerve conduction velocity and synaptic efficacy along the neonatal auditory nerve and brain-stem. This differential evaluation may enable more accurate determination of developmental age of neonates, with respect to total maturation as well as its constituents.

Sound lateralization and interaural discrimination. Effects of brainstem infarcts and multiple sclerosis lesions.

Subjects with brainstem lesions due to either an infarct or multiple sclerosis (MS) underwent two types of binaural testing (lateralization testing and interaural discrimination) for three types of sounds (clicks and high and low frequency narrow-band noise) with two kinds of interaural differences (level and time). Two major types of abnormalities were revealed in the lateralization performances: perception of all stimuli, regardless of interaural differences (time and/or level) in the center of the head (center-oriented), or lateralization of all stimuli to one side or the other of the head (side-oriented). Similar patterns of abnormal lateralization (center-oriented and side-oriented) occurred for MS and stroke patients. A subjects pattern of abnormal lateralization testing was the same regardless of the type of stimulus or type of interaural disparity. Lateralization testing was a more sensitive test than interaural discrimination testing for both types of subjects. Magnetic resonance image (MRI) scanning in three orthogonal planes of the brainstem was used to detect lesions. A semi-automated algorithm superimposed the auditory pathway onto each MRI section. Whenever a lesion overlapped the auditory pathway, some binaural performance was abnormal and vice versa. Given a lateralization test abnormality, whether the pattern was center-oriented or side-oriented was mainly determined by lesion site. Center-oriented performance was principally associated with caudal pontine lesions and side-oriented performance with lesions rostral to the superior olivary complex. For lesions restricted to the lateral lemniscus and/or inferior colliculus, whether unilateral or bilateral, just noticeable differences (JNDs) were nearly always abnormal, but for caudal pontine lesions JNDs could be normal or abnormal. MS subjects were more sensitive to interaural time delays than interaural level differences particularly for caudal pontine lesions, while stroke patients showed no differential sensitivity to the two kinds of interaural differences. These results suggest that neural processing of binaural stimuli is multilevel and begins with independent interaural time and level analyzers in the caudal pons.

LTP-like changes induced by paired associative stimulation of the primary somatosensory cortex in humans : source analysis and associated changes in behaviour

Paired associative stimulation (PAS), which combines repetitive peripheral nerve stimulation with transcranial magnetic stimulation (TMS), may induce neuroplastic changes in somatosensory cortex (S1), possibly by long‐term potentiation‐like mechanisms. We used multichannel median nerve somatosensory evoked potential (MN‐SSEP) recordings and two‐point tactile discrimination testing to examine the location and behavioural significance of these changes. When TMS was applied to S1 near‐synchronously to an afferent signal containing mechanoreceptive information, MN‐SSEP changes (significant at 21–31 ms) could be explained by a change in a tangential source located in Brodmann area 3b, with their timing and polarity suggesting modification of upper cortical layers. PAS‐induced MN‐SSEP changes between 28 and 32 ms were linearly correlated with changes in tactile discrimination. Conversely, when the near‐synchronous afferent signal contained predominantly proprioceptive information, PAS‐induced MN‐SSEP changes (20–29 ms) were shifted medially, and tactile performance remained stable. With near‐synchronous mechanoreceptive stimulation subtle differences in the timing of the two interacting signals tended to influence the direction of tactile performance changes. PAS performed with TMS delivered asynchronously to the afferent pulse did not change MN‐SSEPs. Hebbian interaction of mechanoreceptive afferent signals with TMS‐evoked activity may modify synaptic efficacy in superficial cortical layers of Brodmann area 3b and is associated with timing‐dependent and qualitatively congruent behavioural changes.

Pseudobulbar affect: the spectrum of clinical presentations, etiologies and treatments

Pseudobulbar affect (PBA) consists of uncontrollable outbursts of laughter or crying inappropriate to the patient’s external circumstances and incongruent with the patient’s internal emotional state. Recent data suggest disruption of cortico–pontine–cerebellar circuits, reducing the threshold for motor expression of emotion. Disruption of the microcircuitry of the cerebellum itself may likewise impair its ability to act as a gate-control for emotional expression. Current evidence also suggests that serotonergic and glutamatergic neurotransmission play key roles. Although antidepressants have shown benefit, the supportive clinical data have often derived from small numbers of patients and unvalidated measures of PBA severity. Dextromethorphan/quinidine, the first FDA-approved PBA medication, is a novel therapy with antiglutamatergic actions. As life expectancy lengthens and the neurologic settings of PBA become more common, the need for treatment can be expected to increase.