From brainstem to cortex: neurobiologic research provides keys to the riddles, mysteries and enigmas of brain dysfunction.
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Auditory Perception↗
Biomedical subjects
G C Galbraith
Publications and source records attributed to G C Galbraith.
Brainstem frequency-following response recorded from one vertical and three horizontal electrode derivations.
The human brainstem frequency-following response reflects neural activity to periodic auditory stimuli. Responses were simultaneously recorded from one vertically oriented and three horizontally oriented electrode derivations. Nine participants each received a total of 16,000 tone repetitions, 4,000 for each of four stimulus frequencies: 222, 266, 350, and 450 Hz. The responses were digitally filtered, quantified by correlation and spectral analysis, and statistically evaluated by repeated measure analysis of variance. While the various horizontal derivation responses did not differ from each other in latency (values tightly clustered around M= 2.60 msec.), the vertical derivation response occurred significantly later (M=4.38 msec.). The smaller latency for the horizontal responses suggests an origin within the acoustic nerve, while the larger latency for the vertical response suggests a central brainstem origin. The largest response amplitude resulted from gold "tiptrode" electrodes placed in each auditory meatus, suggesting that this electrode derivation provided the most accurate (noninvasive) assessment of short-latency events originating at the level of the auditory nerve.
Adult↗
Enhanced brainstem and cortical evoked response amplitudes: single-trial covariance analysis.
The purpose of the present study was to develop analytic procedures that improve the definition of sensory evoked response components. Such procedures could benefit all recordings but would especially benefit difficult recordings where many trials are contaminated by muscle and movement artifacts. First, cross-correlation and latency adjustment analyses were applied to the human brainstem frequency-following response and cortical auditory evoked response recorded on the same trials. Lagged cross-correlation functions were computed, for each of 17 subjects, between single-trial data and templates consisting of the sinusoid stimulus waveform for the brainstem response and the subject's own smoothed averaged evoked response P2 component for the cortical response. Trials were considered in the analysis only if the maximum correlation-squared (r2) exceeded .5 (negatively correlated trials were thus included). Identical correlation coefficients may be based on signals with quite different amplitudes, but it is possible to assess amplitude by the nonnormalized covariance function. Next, an algorithm is applied in which each trial with negative covariance is matched to a trial with similar, but positive, covariance and these matched-trial pairs are deleted. When an evoked response signal is present in the data, the majority of trials positively correlate with the template. Thus, a residual of positively correlated trials remains after matched covariance trials are deleted. When these residual trials are averaged, the resulting brainstem and cortical responses show greatly enhanced amplitudes. This result supports the utility of this analysis technique in clarifying and assessing evoked response signals.
Adolescent↗
Putative measure of peripheral and brainstem frequency-following in humans.
The human brainstem frequency-following response (FFR) registers phase-locked neural activity to periodic auditory stimuli. FFR waveforms were extracted from the electroencephalogram by averaging responses to repeated auditory stimulation. Two channels of data were simultaneously recorded from horizontally (electrodes placed in ear canals) and vertically (vertex scalp referenced to midline) oriented electrode configurations. Eight participants each received a total of 2000 tone repetitions for each of ten stimulus frequencies ranging from 133 to 950 Hz. FFRs were quantified by fast-Fourier spectral analysis. The largest spectral intensities at the stimulus frequency were recorded in the horizontal FFR, which also followed higher frequencies and showed better signal-to-noise ratios then did the vertical FFR. The horizontal FFR pattern suggests an acoustic nerve origin, while the vertical FFR pattern suggests a central brainstem origin.
Acoustic Stimulation↗
Individual differences in autonomic activity affects brainstem auditory frequency-following response amplitude in humans.
Innervation of the cochlea by sympathetic fibers suggests that the autonomic nervous system (ANS) may influence auditory information processing. The brainstem frequency-following response (FFR) and spontaneous skin conductance activity (SCA) were measured while subjects discriminated between long (rare) and short (frequent) duration tones. When subjects were divided into three groups on the basis of SCA, those with low SCA variability had larger FFR amplitudes. These results agree with the only other study to report ANS effects on brainstem auditory evoked responses [28]. It is proposed that individual differences in autonomic response patterns may account for some of the amplitude variation reported in brainstem evoked potential studies.
Acoustic Stimulation↗
Brainstem frequency-following response and simple motor reaction time.
Simple motor reaction times (RT) in humans show marked trial-to-trial variations. In the present study, a brief tone (400 Hz, 37.5 ms duration) that was the imperative stimulus in a RT paradigm evoked the brainstem frequency-following response (FFR). Horizontal and vertical montage FFRs were recorded to evaluate neural responses with putative origins in auditory nerve and central brainstem, respectively. The main question concerned the possible relationship between trial-to-trial variations in RT speed and FFR response properties. The results showed a reliable pattern in which fast RT trials yielded larger amplitudes (relative to slow trials) in earlier milliseconds of the FFR, and slow RT trials yielded relatively larger amplitudes in later milliseconds of the response. These results support the conclusion that early processing in the auditory brainstem is not automatic and invariant. Rather, short-latency evoked potentials appear to reflect trial-to-trial variations related to events far removed from the first synapse of sensory coding, perhaps depending upon cortically mediated influences such as cognition or attention.
Acoustic Stimulation↗
Brain stem frequency-following response to dichotic vowels during attention.
Frequency-following responses (FFRs) were elicited by English long vowels (female /a/ and male /e/) in a dichotic listening task. Stimuli were simultaneous and of equal duration, but differing spectra permitted unique identification of vowel components in the compound FFR. Horizontal and vertical montage FFRs were recorded with putative origins in the acoustic nerve and central brain stem, respectively. FFRs obtained during attention to each vowel showed significant effects for the voice fundamental frequency, f0, which is perceptually salient and conveys paralinguistic information such as the sex of the speaker. Amplitudes of f0 were larger when vowels were attended than when ignored. These findings provide evidence of short-latency attention effects in humans and suggest that linguistic attention may initially filter inputs based on salient paralinguistic cues.
Acoustic Stimulation↗
Interhemispheric transfer in normals and acallosals: latency adjusted evoked potential averaging.
Interhemispheric transfer time (IHTT) can be estimated from visual evoked potentials (EPs). Latency adjusted averaging (LAA) produces EPs which have enhanced components. LAA also provides estimates of EP latency variance and signal-to-noise ratio (S/N). LAA was tested in analysis of EP-IHTT in normal and acallosal subjects. It was hypothesized that in normals S/N and latency variance would reveal signal degradation resulting from interhemispheric transfer. LAA in normals replicated IHTT findings for both P1 and N1 latency. Latency variance did not increase for cross-callosal measures, whereas the S/N measure showed significant EP degradation due to callosal transfer. EPs from five subjects with callosal absence (two commissurotomy; two complete and one partial callosal agenesis) showed significantly larger than normal latency variability, as well as decreased S/N ratios, for cross-hemisphere visual EPs. Results support the value of LAA in EP research on adequacy of hemispheric interactions in clinical populations.
Adolescent↗
Speech-evoked brainstem frequency-following responses during verbal transformations due to word repetition.
Speech-evoked brainstem frequency-following responses (FFRs) were recorded to repeated presentations of the same stimulus word. Word repetition results in illusory verbal transformations (VTs) in which word perceptions can differ markedly from the actual stimulus. Previous behavioral studies support an explanation of VTs based on changes in arousal or attention. Horizontal and vertical dipole FFRs were recorded to assess responses with putative origins in the auditory nerve and central brainstem, respectively. FFRs were recorded from 18 subjects when they correctly heard the stimulus and when they reported VTs. Although horizontal and vertical dipole FFRs showed different frequency response patterns, dipoles did not differentiate between perceptual conditions. However, when subjects were divided into low- and high-VT groups (based on percentage of VT trials), a significant Condition x Group interaction resulted. This interaction showed the largest difference in FFR amplitudes during VT trials, with the low-VT group showing increased amplitudes, and the high-VT group showing decreased amplitudes, relative to trials in which the stimulus was correctly perceived. These results demonstrate measurable subject differences in the early processing of complex signals, due to possible effects of attention on the brainstem FFR. The present research shows that the FFR is useful in understanding human language as it is coded and processed in the brainstem auditory pathway.
Adolescent↗
Brainstem frequency-following responses in Rett syndrome.
The brainstem frequency-following response (FFR) is a short-latency evoked response that reflects waveform properties of periodic auditory stimuli. Unlike neural activity evoked by transient stimuli, the FFR originates in phase-locked neurons that provide unique information concerning the early processing of auditory inputs. FFRs elicited by a pure tone were recorded from 9 Rett syndrome patients (age 26-55 years, mean = 34.4 years) and compared with those of 18 normal infants (age 2-10 months, mean = 5.0 months), and 113 young adult (age 18-30 years, mean = 22.2 years) controls. The Rett syndrome pattern indicated considerable intersubject latency variability and poor intrasubject repeat reliability except for brief FFR components which were consistently synchronized. The pattern observed in Rett syndrome was similar in certain respects to that observed in infants, but both patterns differed from those of adults, who showed larger amplitudes and consistent waveform synchrony. Clinical and neuropathologic data indicate developmental arrest rather than a neurodegenerative process in Rett syndrome. The present results are consistent with this interpretation. Neurophysiologic studies may identify markers that are distinctive in Rett syndrome and make it possible to monitor changes with age and disease process.
Adolescent↗
Intelligible speech encoded in the human brain stem frequency-following response.
The human brain stem frequency-following response (FFR) registers phase-locked neural activity to cyclical auditory stimuli. We show that the FFR can be elicited by word stimuli, and when speech-evoked FFTs are reproduced as auditory stimuli they are heard as intelligible speech. Stimuli were 10 high- and 10 low-probability words drawn from normative verbal responses of university students. Horizontal and vertical dipole FFRs based on 1000 repetitions of each word were recorded from two different participants. Speech-evoked FFRs were evaluated by 80 listeners. The results showed significant effects of FFR participant, word probability, and whether or not words were presented with category cues. Depending on such subject and experimental variables, FFRs were correctly perceived from 5% to 92% of the time.
Acoustic Stimulation↗
Brainstem frequency-following and behavioral responses during selective attention to pure tone and missing fundamental stimuli.
Reaction time (RT), discrimination sensitivity (d'), and the brainstem frequency-following response (FFR) were recorded in 32 subjects performing a selective attention task. Auditory stimuli were a 400 Hz pure tone and a complex "missing fundamental" (MF) presented dichotically to separate ears (channels). In two tasks, infrequent target stimuli were either of lower intensity or greater duration than standard stimuli. Behavioral results showed consistently better performance (faster RTs and higher d' scores) in the duration task, and better overall detection of MF targets. FFR attention effects were evidenced by differing amplitudes in attend and ignore conditions. Amplitudes in the attended channel were larger to MF stimuli in both tasks, and to the tone stimulus in the duration task. Responses to tone in the intensity task, however, were lowest when the channel was attended, perhaps reflecting some property of greater task difficulty. The demonstration of FFR amplitude differences between attended and ignored channels suggests that selective attention can modify brainstem evoked responses in humans.
Acoustic Stimulation↗
Two-channel brain-stem frequency-following responses to pure tone and missing fundamental stimuli.
In 2 separate experiments the brain-stem frequency-following response (FFR) was recorded to a pure tone (200 Hz) and complex "missing fundamental" (MF) stimuli differing in temporal fine structure and envelope modulation depth. FFRs were simultaneously recorded in 2 channels with horizontal and vertical dipole orientations. Horizontal electrodes were identical in both experiments (right-left ear), but the vertical configuration was varied (vertex-left ear; vertex-linked mastoids). The horizontal channel yielded a well defined FFR to tone stimulation at a latency consistent with an origin along the auditory nerve. However, there was no horizontal response to MF stimulation. This latter finding provides electrophysiological support for the conclusion that MFs are not directly coded in the peripheral neural response. Vertical recordings, however, showed equally well defined FFRs to tone and MF stimuli. Thus, a representation of the missing fundamental frequency is registered in the brain-stem. Vertical latencies were consistent with a source at the level of the lateral lemniscus. The FFR is well suited to elucidate certain brain-stem mechanisms of auditory information processing. Important additional information results when responses are compared in horizontal and vertical dipole orientations. Thus, the present results provide the first evoked response demonstration of a peripheral-brain-stem dichotomy of MF coding.
Acoustic Stimulation↗
Selective attention and brainstem frequency-following responses.
In the auditory system, cortical event-related potential amplitudes are enhanced during selective attention within the auditory channel. In the case of brainstem responses, however, the results are less clear since only a few studies have reported attention effects. Nearly all of these studies have used click stimuli to elicit the brainstem auditory evoked response (BAER). In the present study, pure tones (200 and 400 Hz) elicited the brainstem frequency-following response (FFR) in a task that maximized channel separation by presenting different frequencies to each ear. Twelve male and 12 female subjects participated. Perceptual sensitivity (d') showed an overall right ear advantage (REA) that did not depend on gender or stimulus frequency. FFR averages were enhanced by digital filtering, the 25 ms response was partitioned in half, and quantified by fast-Fourier analysis. Results of the statistical analysis showed a significant Attention x Frequency x Half interaction. Thus, whether or not component amplitudes were larger during attention depended on the particular stimulus and temporal location within the FFR. These results are more complex and time variant than would be predicted by the hypothesis that attention only enhances evoked response amplitudes. Nevertheless, these results suggest that some form of attention-related modulation may be occurring at the level of the brainstem. The present results provide additional support for a peripheral gating mechanism in humans, which has been claimed in a minority of BAER studies. The FFR may provide additional useful information since it presumably depends on phase-locking neural elements, rather than on-units activated by acoustic transients.
Adult↗
Moment analysis of EEG amplitude histograms and spectral analysis: relative classification of several behavioral tasks.
Previous studies indicate that EEG amplitude probability density functions are Gaussian (normal) during rest and non-Gaussian during performance of mental tasks. In the present study we compared measures of normality, including higher central moments (e.g., skewness, kurtosis) and relative spectral power, to classify data sampled from several different behavioral tasks (resting eyes closed and mental arithmetic). Analysis shows significant classification in 22 of 25 subjects, based upon a total of 46 EEG variables. However, only two of these variables involved Gaussian properties of the amplitude distribution. Relative spectral power, on the other hand, contributed 33 predictor variables in delta, theta, alpha, and beta frequency bands (alpha was the best single predictor). These results lend support to studies demonstrating the robustness of EEG relative spectra but cast doubt upon the utility of Gaussian patterns in EEG amplitude distributions as predictors of behavioral states.
Adult↗
Brainstem frequency-following responses and cortical event-related potentials during attention.
Human brainstem frequency-following responses (FFRs) and cortical event-related potentials (ERPs) were evoked by a low-frequency (230 Hz) tone during directed attention. ERPs showed significant amplitude differences consistent with expected attention effects, viz., largest to attended stimuli and smallest to ignored stimuli. The ERP data thereby confirm that attention effectively modulated cortical responses. The FFR, however, did not differ between conditions. The present results agree with one earlier FFR study and a majority of studies using click stimuli to elicit the brainstem auditory evoked response (BAER). However, several BAER studies and two recent FFR studies have shown that attention can influence human brainstem responses. The present results are therefore interpreted in the context of specific task requirements that optimize early selective attention effects.
Adolescent↗
Perceptual adaptation in the vestibulo-ocular system: EEG correlates of spatial and temporal rearrangement.
Spatial-temporal visuomotor rearrangement caused pursuit eye movements to counteract the vestibulo-ocular reflex (VOR). Vertical head nodding produced horizontal oscillations of a light spot delayed 1 or 150 msec. Adaptation resulted in apparent complementary motion of a stationary stimulus during nodding. 16 subjects adapted and tested at 150 msec. showed a 10% magnitude apparent motion. Following normal vision, while the electroencephalogram (EEG) was recorded, subjects were readapted at 150 msec. but tested at 1 msec. (to measure temporal generalization). Individual performance was correlated with EEG alpha. Adaptation correlated negatively with O(z) and Fz intensity, and positively with O(z) frequency. Temporal generalization correlated positively with O(z) intensity and negatively with O(z)-Fz phase angle. These results suggest that visuomotor adaptability is related to electrocortical activity.
Adult↗
Latency compensation analysis of the auditory brain-stem evoked response.
Latency compensation analysis (LCA) was applied to single trial samples of the auditory brain-stem evoked response (ABR, IV-V complex). By this means it was possible to characterize properties of temporal variability in the ABR, including certain cases of temporal outliners. A lagged cross-correlogram analysis provided information for each trial that included the largest r2 and associated lead/lag value. The distribution of lag values (based on all trials) was statistically different when ABRs were evoked by stimuli differing by 5 dB. Recomputing the ABR by eliminating temporal outliers, and by adjusting for temporal variability, showed a range of individual patterns of increased amplitude. However, a comparison of Down syndrome (DS) and non-retarded individuals showed a significantly greater amplitude increase in the DS group after LCA. This suggests that certain forms of mental retardation may be characterized by reduced stability in a neural system that is thought to depend upon 'synaptically secure' neurons.
Brain Stem↗