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[Neurophysiology of parkinsonian syndromes].

Neurophysiological investigations may contribute to establish the diagnosis of different parkinsonian syndromes such as multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, which are often suspected in case of atypical parkinsonian syndrome. They provide a means of objective analysis of certain symptoms (myoclonus for example) and identify the pathophysiological processes underlying these parkinsonian syndromes. This article reviews especially the following electrophysiological tests: autonomic nervous system analysis (sympathetic sudomotor skin response, R-R interval variation, electromyography of the external anal sphincter), surface electromyography and movement recording to investigate myoclonus, somatosensory and motor evoked potentials, brainstem reflexes (mainly the blink reflex), startle reaction, monosynaptic and long latency reflexes and finally the premotor potentials (contingent negative variation, Bereitschaftspotential) and movement-related desynchronization).

Anal Canal↗

CNV evidence for the distinctiveness of frontal and posterior neural processes in a traumatic brain-injured population.

The association between certain behavioral tests of executive functions in humans and the integrity of the prefrontal lobes has rested primarily on studies comparing subjects with frontal versus other loci of damage. Another approach is to compare the within-group variation on a physiological index of frontal functioning with the behavioral tests of interest. In the present study, subjects with traumatic brain injury (TBI) were given four behavioural measures of executive function, two measures of posterior nonexecutive function, and a Contingent Negative Variation (CNV) task, a proposed electrophysiological index of frontal-lobe functioning. We found that three of the four executive function tests were significantly related to the CNV, accounting for 23-52% of the variance, while the CNV did not correlate at all with the posterior tasks.

Adolescent↗

Being prepared on time: on the importance of the previous foreperiod to current preparation, as reflected in speed, force and preparation-related brain potentials.

How do participants adapt to temporal variation of preparatory foreperiods? For reaction times, specific sequential effects have been observed. Responses become slower when the foreperiod is shorter on the current than on the previous trial. If this effect is due to changes in motor activation, it should also be visible in force of responses and in EEG measures of motor preparation, the contingent negative variation (CNV) and the lateralized readiness potential (LRP). These hypotheses were tested in a two-choice reaction task, with targets occurring 500, 1500, or 2500 ms after an acoustic warning signal. The reaction time results showed the expected pattern and were accompanied by similar effects on a fronto-central CNV and the LRP. In contrast, the increase of response force with brief current foreperiods did not depend on previous foreperiods. Thus, EEG measures confirm that sequential effects on RT are at least partially due to changes in motor activation originating from previous trials. Effects found on response force may be related to general response readiness rather than activation of motor-hand areas, which may explain the absence of a sequential effect on force in the current experiment.

Adult↗

Changing plans: a high density electrical mapping study of cortical control.

High density electrical mapping was used to index event-related brain activity in subjects performing parametric variations of the "AX"-type continuous performance task (AX-CPT) that differentially challenge control, and informative control conditions. In the AX-CPT, subjects must use context, created by a cue stimulus, to guide response to a target. Diseases such as schizophrenia and attention deficit hyperactivity disorder (ADHD) are associated with impaired AX-CPT performance. Event-related potentials (ERP) were analyzed as a function of both global and local stimulus context. The topographical analysis revealed that well-defined ERP are elicited under conditions where subjects must override a prepotent response. Activation patterns related to overriding a prepotent response (Go to No-Go) differed markedly from those associated with overriding a prepotent non-response (No-Go to Go). Dipole source mapping suggested that withholding a prepotent response is reflected primarily in anterior cingulate/dorsolateral prefrontal cortex activity during the 350-450 ms latency range following presentation of the No-Go. In contrast, preparing to respond is reflected in parietal (including area BA 40) activity during the same latency range, followed by a prolonged frontal negativity (contingent negative variation; CNV). Similar patterns of activation were observed whether the changes in preparation were triggered by cue or target stimuli, though target-elicited potentials peaked earlier.

Adolescent↗

Frontal and parietal premovement slow brain potentials in Parkinson's disease and aging.

During the anticipation of a stimulus that induces a predetermined pattern of behavior, a slowly increasing negative electric potential can be recorded from the human scalp at central and parietal electrodes and has been named contingent negative variation (CNV). We used a simple and a choice reaction time paradigm to investigate premovement potentials in patients with Parkinson's disease (PD) and in normal controls. There was a clear CNV in young subjects whereas it was negligible in the elderly control subjects and absent in the patients. In addition, we found a slowly increasing positive frontal potential. In normals the steepness of this potential decreased with the complexity of the task (simple vs. choice) and with age. This difference was abolished in the patients: If a slowly increasing positivity was observed at all, it was, on average, larger in the choice task. Reaction times of the patients were disproportionally prolonged in the simple compared to the complex task. These findings support the hypothesis that storing or initiating a simple preprogrammed motor response is more impaired in PD than selecting and initiating a motor response of a more complex task. The electrophysiological recordings suggest that impaired activation of the frontal lobes may be responsible for this deficit.

Age Factors↗

Self-regulation of slow cortical potentials in psychiatric patients: depression.

Findings on depressive patients indicate that depressives have electrophysiological characteristics similar to those of schizophrenics, in that they exhibit reduced Contingent Negative Variation (CNV) amplitudes and more distinct Postimperative Negative Variations (PINVs) than normal controls. In a biofeedback experiment, 8 medicated male inpatients with the DSM III-R diagnosis of "Bipolar Disorder, Depressive," and "Major Depression" demonstrated no impairment in the self-regulation of Slow Cortical Potentials (SCP) in comparison to schizophrenics in terms of increasing and suppressing negativity. Continuous visual SCP feedback is presented to the patient as a horizontally moving rocket in a video game format. The direction changes of the rocket represented SCP changes at each point in time, recorded by the central EEG (based on the pretrial baseline). Depressives demonstrated SCP self-regulation across 20 sessions, although with many between-and-within variations. The 8 male controls were unable to regulate their SCPs across 5 sessions. This result contradicts other findings of our laboratory on normal controls. Motivational factors and insufficient operant reinforcement (financial reward) may have facilitated this effect.

Adult↗

Pharmacokinetic and pharmacodynamic responses to caffeine in poor and normal sleepers.

Pharmacokinetic and pharmacodynamic responses to caffeine (2.5 mg/kg) were compared between ten healthy self-rated poor sleepers and ten normal sleepers. Sleep pattern assessed by the Pittsburgh Sleep Quality Index (PSQI). There was no significant difference in mean estimated daily caffeine consumption between the groups. The poor sleepers had significantly higher scores for neuroticism on the Eysenck Personality Questionnaire (EPQ) and anxiety on the Hospital Anxiety Depression (HAD) scale, compared with normal sleepers. Caffeine pharmacokinetics were assessed by measurement of saliva caffeine concentrations. Poor sleepers showed significantly greater variability in caffeine Cmax, clearance had half-life, compared to normal sleepers. Pharmacodynamic measures included heart rate, blood pressure, visual analogue scales for concentration, vigilance and relaxation, psychomotor performance [Digit Symbol Substitution Test (DSST) and tapping rate (TR)] and EEG activity [Contingent negative variation (CNV), auditory evoked potential and power spectral analysis]. Prior to caffeine administration, poor sleepers compared to normal sleepers had faster heart rates, lower ratings for concentration and relaxation, poorer performance on the DSST, greater CNV magnitude, faster peak alpha frequency and lower delta, theta and beta power. These differences persisted after caffeine ingestion and overall differences between the groups on these measures were significant (P < 0.01-.001). Post-dose, but not pre-dose, scores for vigilance and TR were significantly lower overall in poor compared with normal sleepers. Despite the baseline differences between poor and normal sleepers, the changes following caffeine administration were similar in direction and magnitude in both groups.

Adult↗

Cognitive event-related potentials and reaction time in presenile subjects with initial mild cognitive decline or probable Alzheimer-type dementia.

The so-called contingent negative variation (CNV) is a slow brain potential representing a complex of variously overlapped "endogenous" components of behavior related to different reasonably well-known neurocognitive processes. CNV complex evoked with a standard paradigm (S1-2 sec-S2-motor response) and reaction time (RT) to imperative signal (S2) were recorded and measured in 11 patients with initial presenile idiopathic cognitive decline (PICD), 8 with presenile Alzheimer-type dementia (PAD) and 10 healthy age-matched controls. Significant group differences were obtained for measures of some CNV components, particularly of the late pre-S2 CNV. No significant CNV activity, very prolonged RTs and sometimes characteristic post-imperative negative variation (PINV) were observed in the majority of patients with PAD. These results suggest that CNV complex and RT changes similar to those observed in our patients may constitute a valuable clue for the study of pathophysiological brain functioning in the early stages of presenile idiopathic mental deterioration.

Aged↗

Spectral analysis of EEG responses.

The techniques used and the results obtained in a spectral analysis of two specific responses in the human electroencephalogram are presented in this paper. The purposes are to show how the techniques may be applied to the necessarily short lengths of EEG data and to illustrate these techniques and the useful results obtained by relevant examples. The necessary data-processing procedures and precautions for transforming from the time to frequency domain are presented in a tutorial fashion. The importance of augmenting zeros, choice of the most appropriate data window and pretransformation of the data to avoid the combined effects of energy loss and low frequency content biasing caused by windowing is explained. The pros and cons of the tapered-cosine (Tukey) and Kaiser-Bessel windows are illustrated. The usefulness of applying certain statistical tests, which are based on a physical model of the responses, to the harmonic components of the responses is demonstrated. Thus a comparison is made between the features of auditory evoked responses and of the contingent negative variation, and the usefulness of predictive statistical diagnosis in differentiating between subject groups is illustrated by application to normal subjects and Huntington's chorea patients.

Biomedical Engineering↗

Movement-related potentials associated with self-paced, cued and imagined arm movements.

Self-paced movements, movement to a cue and imagined movement have all been reported to be preceded by a prolonged negativity on averaged electroencephalograph (EEG) recordings. Considerable evidence supports an important contribution from the supplementary motor area (SMA) to this potential and all three types of movement have been shown to be associated with SMA activation. This study was designed to compare the premovement component of these movement-related potentials (MRPs) in a group of subjects who performed each of these three types of movement. In addition, in view of the greater SMA activation in association with proximal arm movements, we studied movements at multiple joints in the right arm. All the potentials were largest at Cz. Self-paced movements were preceded by a negativity (mean onset 1.2 s prior to electromyographic activity) with two distinct phases - an early slow increase (early BP, Bereitschaftspotential) and a later, steeper phase (NS', negative slope). Proximal movements were associated with a larger peak amplitude (mean peak amplitude for shoulder 11.6 micro V, finger movement 9.0 micro V at Cz, n=14) due to a bigger NS' phase. Movements to a regular cue, but not to a randomly timed cue, were also preceded by a long duration negativity, but the NS' phase began earlier and was less distinct than for self-paced movements (mean peak amplitude for shoulder movement 9.1 micro V, finger 8.2 micro V at Cz, n=12). Imagining the movements to a regular cue was associated with a slow negativity, with no clear NS' phase (mean peak amplitude for shoulder movement 6.5 micro V, finger 6.2 micro V at Cz). Our results indicate that the MRPs prior to the three types of movement have distinct characteristics, most notably for the NS' phase. The MRP associated with movement to a regular cue may be analogous to the S2-related negativity of the contingent negative variation (CNV). We discuss the findings in the light of current evidence from functional imaging as to the cortical areas activated in similar movements.

Adult↗

Pathophysiology of tics and Tourette syndrome.

Tics are involuntary movements that can affect one or more muscles producing simple or complex movements. Blink reflex and startle reflex studies disclose an increased excitability of brainstem interneurons. Analysis of voluntary movement shows that when advance visual information is reduced, patients with tics and Tourette syndrome become progressively slower in completing motor sequences. Sensorimotor integration is abnormally processed. Studies of the contingent negative variation demonstrate abnormalities of movement preparation and the investigation of premotor potentials shows that in some patients tics are not preceded by a normal premotor potential. Magnetic stimulation studies demonstrate an increased excitability of cortical motor cortex. Functional MRI, PET and SPECT studies show abnormal activation of cortical and subcortical areas. Dysfunction of basal ganglia-thalamo-cortical projections affects sensorimotor, language and limbic cortical circuits, and may explain why patients with Tourette syndrome have difficulty in inhibiting unwanted behaviors and impulses.

Animals↗

[Duration of migraine disease correlates with amplitude and habituation of event-related potentials].

BACKGROUND: Duration of a migraine disease and hypervigilance are factors which possibly enable the transformation from episodic into chronic migraine. To elucidate this assumption, attentional parameters were measured by recording contingent negative variation (CNV) and correlated with the individual duration of migraine disease. PATIENTS AND METHODS: A total of 28 patients (episodic migraine with or without aura) were compared with 16 healthy controls. CNV analysis included amplitude and habituation calculation. Data were correlated with the individual duration of the migraine disease. The migraine group was divided into two groups based on a median split (short vs long lasting) which were compared by t-tests. RESULTS: Migraine patients produce higher CNV amplitudes than controls. Moreover, migraineurs showed dishabituation while habituation was seen in controls. There was a Pearson correlation coefficient of r = -0.767 between duration of disease and early component of CNV. Patients with long-lasting disease showed lower dishabituation by a higher intercept than patients with short-lasting disease. CONCLUSION: The correlation between duration of disease and attentional parameters and the changing dishabituation can be interpreted as an enhancement in preactivation level in patients with long-lasting migraine. Maybe this change is a prerequisite for transformation into chronic migraine.

Evoked Potentials↗

Continuous-processing--related event-related potentials in children with attention deficit hyperactivity disorder.

Visual information processing in children with attention deficit hyperactivity disorder (ADHD) was studied using event-related potentials recorded during two versions of the Continuous Performance Task (CPT). ADHD children made more errors, and had longer reaction times than normal children on both the single- and dual-target CPT. Event-related potential waveforms were normal in the ADHD children with reference to early processing stages, i.e., contingent negative variation, P1-N1 laterality, and processing negativities, suggesting that ADHD children did not differ in their level of preparedness or their ability to mobilize resources for target identification and categorization. With respect to later processing, P3 amplitude was reduced in the ADHD group, whereas P3 latency was longer than normal. ADHD children had a diminished late frontal negative component, suggestive of reduced involvement in postdecisional processing.

Adolescent↗

Human auditory sustained potentials. I. The nature of the response.

In response to a sustained toneburst a negative baseline shift can be recorded from the human fronto-central scalp regions with an onset latency of approximately 150 msec. This auditory sustained potential is distinct both in its scalp distribution and in its stimulus relationships from the transient response occurring at the onset or offset of the toneburst. It differs from the contingent negative variation in that it can occur in the absence of attention or during sleep. Attention to the auditory stimulus can increase the amplitude of the sustained potential, possibly through the addition of an extra negative potential related to auditory expectancy or uncertainty.

Adolescent↗

Slow brain potentials and psychomotor retardation in depression.

Event-related cortical potentials were recorded in 11 patients with primary depression and 11 healthy control subjects during a serial choice reaction task. Each new trial was voluntarily initiated when the subject pressed a microswitch; an acoustic go or no-go signal followed after a fixed interval. This elicited a Bereitschaftspotential (BP), a contingent negative variation (CNV), acoustically evoked potentials (N1, P2, P3), and a post-imperative negative variation (PINV) in direct succession. These were evaluated conventionally and by principal component analysis (PCA). Patients exhibited significantly longer reaction times and more negative PINVs. BP and CNV did not differ between groups. In conventional amplitude measurement small P3 amplitudes in depressives may be feigned by markedly negative PINVs.

Adult↗

The generation of cortical slow potentials in the rat anaesthetised with urethane and their modification by nicotine.

This paper reports the generation of cortical slow potentials (SP), similar to the human contingent negative variation, in rats anaesthetised with urethane. Rats previously implanted with silver/silver chloride electrodes for recording slow potentials from the frontal cortex were anaesthetised with urethane, and given extensive associative conditioning in which a 100 msec, 70 dB tone (S1) preceded electric tail shock (S2). The S1-S2 interval was initially set at 0.5 sec, and increased over a number of training sessions to 3 sec. Negative slow potential responses developed during the interval between S1 and S2. Once the slow potential response was fully developed, it persisted without habituation during subsequent sessions. Withholding tail shock (S2) resulted in a rapid extinction of the slow potential response to S1 alone. In further experiments, rats (n = 8) that generated steady slow potentials under urethane, were injected with saline (n = 4) or nicotine (0.4 mg/kg, s.c.; n = 4), and their responses measured 0-10, 15-25 and 30-40 min after administration. While saline did not affect the magnitude of the slow potential responses compared with pre-saline control values, nicotine (0.4 mg/kg) caused significant decreases in the magnitude of slow potentials during all the measurement intervals. These results demonstrate that cortical slow potentials can be generated in rats anaesthetised with urethane, and that these slow potentials are sensitive to drugs such as nicotine. The slow potential responses measured in the rat anaesthetised with urethane thus have similar characteristics to those generated in the conscious rat. Such a preparation may therefore prove useful in carrying out experiments on slow potentials that were previously difficult or impossible in conscious animals.

Anesthesia, General↗

Neuronal activities underlying the electroencephalogram and evoked potentials of sleeping and waking: implications for information processing.

The low amplitude, high frequency waves of the electroencephalogram (EEG) indicative of wakefulness, are produced by a summation of potentials of thalamocortical neurons, which fire in a "tonic mode" of depolarization. In this mode, the transfer of information from the peripheral sense organs to the sensory cortex is facilitated, due to a tonic lowering of the discharge threshold of thalamocortical neurons. The transfer decreases during drowsiness when thalamocortical units are more hyperpolarized and have higher thresholds. In this state, neurons fire synchronously in a "burst mode," which is expressed in EEG spindling. During slow wave sleep sensory blocking reaches a maximum, when thalamocortical cells are yet more deeply hyperpolarized, although that what still passes to the cortex allows a shallow, subconscious, evaluation. The collective burst firing is more irregular, which results in large and slow EEG waves. In contrast, during rapid eye movement (REM) sleep the depolarized tonic mode of firing commonly associated with waking, is again reached. Similar to EEG-patterns, the architecture of evoked potentials is dependent on the state of alertness. During waking, components in event related potentials (ERP) are moderate in amplitude, while during slow wave sleep larger waves are visible. This is caused by more synchronized unit responses with sharper phases of excitations and inhibitions, which results from increased hyperpolarizations. In contrast, visual ERPs belonging to REM sleep closely resemble those of wakefulness. In analyzing unit responses of thalamocortical neurons, it appeared that neuronal excitations are expressed in negative components of the ERP, while inhibitory neuronal activities are associated with positivity. Transient phenomena in the EEG, such as ERP waves, spindles and spike-wave discharges, are the expression of synaptic potentials in superficial cortical layers, where numerous synapses of afferent thalamocortical fibers are localized on the apical dendrites of deeper lying pyramidal neurons. It is suggested that the morphology of these EEG components is primarily due to the discharge characteristics of thalamocortical relay cells, whereby excitations underly negative waves and inhibitions positive waves. The notion of a general correspondence between thalamocortical neuronal activities and the polarity of transients in the cortical surface EEG, allows prudent speculations regarding components of ERPs. Two examples are given: the contingent negative variation (CNV) and the P300 of an ERP which can be elicited by an infrequent stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A multidimensional approach in testing nootropic drug effects (Cerebrolysin).

In an attempt to improve indicators of validity for the therapeutic efficacy of nootropics, the effects of Cerebrolysin(R) were compared across three different dimensions of variables in a randomized placebo-controlled double-blind study. A group of 27 geriatric patients suffering from an organic brain syndrome with moderate cognitive impairment of a vascular or/and degenerative nature received a series of ten Cerebrolysin + multivitamin infusions. They were compared to a second group with 14 clinically comparable patients, who received multivitamin infusions alone. Pre-posttreatment differences from (1) clinical scales (SCAG, Plutchik Geriatric Rating Scale and a self-evaluation scale); (2) psychometric test performance (trail-making and maze subtests from the Nürnberg Age Inventory); and (3) event-related brain activity (contingent negative variation (CNV) amplitude) were in favor of the Cerebrolysin-treated group. A high degree of association as well as high classification rates (95% joint correct classification) underlined their clinical significance. It was concluded that the multidimensional measurement approach could increase the clinical validity of nootropic drug effects.

Clinical Trial↗