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Cortico-cortical coupling in Parkinson's disease and its modulation by therapy.

The role of changes in inter-regional cortical synchronization in the pathophysiology of Parkinson's disease and the mechanism of action of dopaminergic therapy and high frequency subthalamic nucleus (STN) stimulation is unclear. We hypothesized that synchronization between distributed cortical areas would correlate with parkinsonism and that changes in synchronization with treatment would correlate with improvements in parkinsonism. To this end, we recorded scalp EEG in parkinsonian patients off treatment (16 patients, 31 sides) and then separately during high frequency stimulation (HFS) of the STN (16 patients, 31 sides) and following drug treatment (12 patients, 24 sides). All recordings were made at rest to avoid the confounding effects of differences in task performance. The motor Unified Parkinson's Disease Rating Scale (UPDRS) score was determined in each state. We found that EEG-EEG coherence over approximately 10-35 Hz correlated with the severity of parkinsonism, and reductions in cortical coupling over this frequency range with both l-dopa and STN stimulation correlated with clinical improvement. These results suggest that both dopaminergic therapy and STN stimulation may support the restoration of normal cortico-cortical interactions in the frequency domain. This mechanistic similarity may underscore the strong clinical correlation between the therapeutic effects of these treatment modalities.

Adult↗

Relationship between oscillations in the basal ganglia and synchronization of cortical activity.

The functions of oscillations within the basal ganglia are poorly understood. We discuss in the present paper, the possible physiological or pathological roles of oscillatory activities within the basal ganglia, and their relationship to cortical oscillations. Three aspects are presented: 1. What do we know from animal studies? 2. What do we know from neurophysiological studies in parkinsonian patients? 3. What is the effect of L-dopa treatment and electrical stimulation within basal ganglia circuits on cortical oscillations? Animal studies suggest that neuronal oscillations are spontaneously generated within the basal ganglia system, especially from the GPE and the subthalamic nucleus (STN), but are mainly synchronized by cortical activity via the striatal inputs. Dopamine depletion results in a global increase of oscillations within the whole basal ganglia system, particularly in the GP-NST network. Oscillations within the basal ganglia may, in part, be related to tremor since they are enhanced, especially in the globus pallidus internus (GPI) and the STN, in human and animal dopaminergic depletion. However, they also play a role in the physiology of movement as revealed by coherence analysis between cortex, muscles and GPI/STN in parkinsonian patients undergoing deep brain stimulation. It is known that the basal ganglia may influence cortico-muscular oscillations such as the Piper rhythm and other rhythms in the beta band. In off-drug parkinsonian patients, low frequency oscillations (4-10 Hz) are favoured, presumably resulting in bradykinesia and low force. When medically (Ldopa) or surgically (deep brain stimulation) treated, these low frequency oscillations are replaced by high frequency (70 Hz) oscillations that are important for motor programs to be correctly executed. Studies of cortical reactivity related to planning of voluntary movement in parkinsonian patients provide evidence that it is possible to influence cortical reactivity through the basal ganglia system.

Animals↗

Rhythmic cortical EEG synchronization with low frequency stimulation of the anterior and medial thalamus for epilepsy.

OBJECTIVE: To investigate the neurophysiological characteristics and prognostic impact of EEG synchronization with low frequency thalamic stimulation in patients with intractable epilepsy. METHODS: Electrical stimuli were delivered through deep brain stimulating (DBS) electrodes at 2, 5 or 10Hz to the anterior nucleus (AN) and the dorsomedial nucleus (DM) of six patients using the implanted programmable stimulation device. EEGs were recorded from 27 scalp electrodes. "Modeled" responses for 5 and 10Hz stimulation were computed based on the cerebral responses (CRs) evoked by "single pulse" (2Hz) stimulation and compared with the recorded EEG results. RESULTS: Rhythmic cortical 5Hz EEG synchronization occurred in 4/6 patients, with stimulation at 6/11 AN and 5/11 DM sites. Three of four patients with synchronization, but neither of the two patients without, had a significant reduction in seizure frequency. The magnitude of 5 and 10Hz EEG synchronization was positively related to the amplitudes of "single pulse" CRs. Simple temporal superposition of "single pulse" CRs resulted in "modeled" responses with strikingly similar morphology and scalp voltage distribution. CONCLUSIONS: Rhythmic EEG synchronization with low frequency stimulation primarily reflects spatiotemporal summation (interference) of "single pulse" CRs. SIGNIFICANCE: Rhythmic EEG synchronization might not serve as a physiologic verification of optimal localization of DBS electrodes. Its usefulness for the prediction of clinical efficacy is questionable.

Adult↗

[The dynamics of the activating and inhibitory types of cortical neuron synchronization during the realization of a defensive reflex and internal inhibition].

In the visual and sensorimotor areas of the neocortex and in the hippocampus of alert nonimmobilized rabbits, in response to combinations of light flashes with electrocutaneous limb stimulation an increase was observed of synchronization in the activity of the near-by neurones by activation by inhibitory type (coincidence of the presence and absence of impulse activity). In response to flashes against the light background--conditioned inhibitor--in the visual cortex synchronization of neurones increased by inhibitory type, and in the sensorimotor cortex and hippocampus changes of synchronization appeared, similar to the action of pain reinforcement but considerably weaker. The increase of synchronization by the activation type took place mainly in the neurones pairs with unidirected increase of impulses frequency and by the inhibitory one--with its decrease. Along with this, in a considerable part of neurones pairs both changes of synchronization appeared at the impulses frequency changes of different direction.

Animals↗

Influence of acetylcholine on shifts in spatial synchronization of cortical potentials of the rabbit, elicited by reversible interruption of the associations of the mammillary bodies.

A decrease in 25 out of 53 calculated coefficients of linear correlation of the potentials between pickups from the visual and motor areas of the cortex, far removed from one another, was observed during anode polarization (20-30 microA, 24 min) of the mammillary nuclei, the column of the fornix, and the mammillothalamic tract, using monopolar 24-channel pickup of the potentials of the cerebral cortex in six rabbits. Application of a 1-2% solution of acetylcholine to the visual area of the cortex leads to an increase in spatial synchronization (13 out of 53 coefficients of correlation) for 5 minutes and between the 10th and 15th minutes from the start of the application. With the combined effect of the polarization of these formations and of the acetylcholine applied to the cortex, reciprocal compensation of the changes in spatial synchronization which wer elicited by each of the influences separately was observed. The hypothesis is advanced of the existence of a nonspecific cholinergic synchronizing system which is active when the mammillothalamocortical connections are preserved.

Acetylcholine↗

Increased synchronization of cortical oscillatory activities between human supplementary motor and primary sensorimotor areas during voluntary movements.

In human, both primary and nonprimary motor areas are involved in the control of voluntary movements. However, the dynamics of functional coupling among different motor areas has not been fully clarified yet. Because it has been proposed that the functional coupling among cortical areas might be achieved by the synchronization of oscillatory activity, we investigated the electrocorticographic coherence between the supplementary motor and primary sensorimotor areas (SMA and S1-M1) by means of event-related partial coherence analysis in 11 intractable epilepsy patients. We found premovement increase of coherence between the SMA proper and S1-M1 at the frequency of 0-33 Hz and between the pre-SMA and S1-M1 at 0-18 Hz. Coherence between the SMA proper and M1 started to increase 0.9 sec before the movement onset and peaked 0.3 sec after the movement. There was no systematic difference within the SMA (SMA proper vs pre-SMA) or within the S1-M1, in terms of the time course as well as the peak value of coherence. The phase spectra revealed near-zero phase difference in 57% (20 of 35) of region pairs analyzed, and the remaining pairs showed inconsistent results. This increase of synchronization between multiple motor areas in the preparation and execution of voluntary movements may reflect the multiregional functional interactions in human motor behavior.

Adolescent↗

EEG and behavioural effects of polyamines (spermine and spermidine) on rabbits.

The EEG and behavioural changes induced by the administration of polyamines (spermine and spermidine) were studied in rabbit. Spermine and spermidine were administered at different doses (200 and 400 micrograms) into the mesencephalic ventricle (i.c.v.) both as a bolus and in constant perfusion (60 min duration). We also studied the effects of methamphetamine (MA) in a group of rabbits pretreated with spermine and spermidine 200 and 400 micrograms i.c.v. as bolus. Spermine caused a dose-related cortical synchronization associated with a partial sedation; spermidine induced cortical synchronization at a low dose without any behavioural changes while at higher dose (after perfusion) cortical desychronization with an arousal behavioural pattern occurred. The possible interaction of these substances with the mesolimbic dopaminergic system is discussed on the basis of their potential neuroleptic action.

Animals↗

Visuomotor integration is associated with zero time-lag synchronization among cortical areas.

Information processing in the cerebral cortex invariably involves the activation of millions of neurons that are widely distributed over its various areas. These distributed activity patterns need to be integrated into coherent representational states. A candidate mechanism for the integration and coordination of neuronal activity between different brain regions is synchronization on a fine temporal scale. In the visual cortex, synchronization occurs selectively between the responses of neurons that represent related features and that need to be integrated for the generation of coherent percepts; neurons in other areas of the cerebral cortex also synchronize their discharges. However, little is known about the patterns and the behavioural correlates of synchrony among widely separated cortical regions. Here we report that synchronization occurs between areas of the visual and parietal cortex, and between areas of the parietal and motor cortex, in the awake cat. When cats responded to a sudden change of a visual pattern, neuronal activity in cortical areas exhibited synchrony without time lags; this synchrony was particularly strong between areas subserving related functions. During reward and inter-trial episodes, zero-time-lag synchrony was lost and replaced by interactions exhibiting large and unsystematic time lags.

Action Potentials↗

[Effect of electric stimulation of non-specific and specific thalamic nuclei on the spatial synchronization of cortical potentials in the rabbit].

The effect of low-frequency (1-10 Hz) electrical stimulation of nonspecific n. centralis lateralis and n. centrum medianum and specific thalamic (LGB) nuclei on spatial synchronization of biopotentials of neocortical areas and on the process of learning was studied on rabbits. Electrical stimulation of the non-specific nuclei raised the level of correlation of the cortical potentials, while the LGB stimulation, on the contrary, weakened the spatial synchronization between the potentials of the visual and sensorimotor neocortical areas. On the basis of the obtained data a conclusion is made that stimulation of the non-specific thalamus contributes to a more successful formation of defensive conditioned reflex to light unlike LGB stimulation. It is suggested that a certain specificity of the studied subcortical formations in organization of spatial synchronization of the brain biopotentials and in the process of learning is due to morpho-functional peculiarities of these structures.

Animals↗

Synchronization of the electrocorticogram by visceral and somatic bradykinin stimulation in anesthetized cats.

The cortical response to visceral and somatic bradykinin stimulation was studied in cats under light to moderate pentobarbital anesthesia. Following the injection of bradykinin into arteries supplying visceral organs and somatic structures, a marked cortical synchronization was recorded. The bilateral, rhythmic discharge in the theta to alpha range was best seen on SI; occasionally the contralateral SI response was more prominent. The cortical synchronization and its distribution were the same for visceral and somatic stimulation. There was only minimal response desensitization to multiple injections of bradykinin in rapid succession. Following transection of the thoracolumbar spinal cord, synchronization failed to develop after hindlimb injections but continued to be seen after forelimb stimulation; similarly, partial denervation of a limb blocked the bradykinin response. No synchronization or desynchronization could be produced by epinephrine and nitroglycerine which caused phasic changes in systemic blood pressure equal to or greater than those seen with bradykinin. The results are discussed in terms of possible pathways and receptors. It is suggested that bradykinin acts primarily on free nerve endings common to visceral and deep somatic tissue with convergence of impulses occurring at spinal and higher levels. The preferential response of SI may reflect afferent activity generated by natural, painful stimulation of deep somatic and visceral organs. Normally, this component would be masked by the concomitant non-specific arousal response of the medial reticulo-thalamic system which was depressed by the anesthetic.

Afferent Pathways↗

A model of cortically induced synchronization in the lateral geniculate nucleus of the cat: a role for low-threshold calcium channels.

Recently Sillito et al. (Nature 1994;369:479-82) discovered correlations in the spike trains of a relatively distant pair of cat lateral geniculate nucleus cells when simultaneously stimulated by a drifting grating; no such correlation occurs when the visual cortex is removed. In a further analysis of the data, we have found that short, high-frequency bursts contribute substantially to the synchronization and we hypothesize that the origin of the bursts is the low-threshold calcium spike. Guided by this hypothesis, our model of the corticogeniculate pathway and early visual system reproduces the experimental data in nearly every detail, as well as making predictions about cortical activity during the synchronizing process. We also discuss the possible behavioral relevance of correlations in the geniculo-cortical loop as well as other neural systems.

Action Potentials↗

Neurobiology of the integrative activity of the brain. Dynamics of the activational and inhibitory types of synchronization of cortical neurons during the realization of a defensive reflex and of internal inhibition.

An increase in synchronization of the activational type (coincidence of the presence of impulse activity), and a decrease of the inhibitory type (coincidence of both the presence and absence of impulse activity), in the operation of close-lying neurons were observed in the visual and sensorimotor areas of the new cortex and in the hippocampus of wakeful non-immobilized rabbits in response to the combination of flashes of light with electrodermal stimulation (EDS) of the extremity. An increase in the synchronization of the neurons of the inhibitory type took place in the visual cortex in response to flashes against the background of the conditional inhibitor, i.e., continuous light, and changes in synchronization, similar to the effect of pain reinforcement but significantly weaker, appeared in the sensorimotor cortex and in the hippocampus. An increase in synchronicity of the activational type took place primarily in pairs of neurons with increase in the same direction in the frequency of impulse activity in response to a stimulus, and of the inhibitory type, took place with its decrease. In addition, both kinds of changes in synchronization appeared in a significant portion of the pairs of neurons with changes in the frequency of impulse activity of different directions.

Animals↗

Contribution of NMDA and nonNMDA glutamate receptors to synchronized excitation and cortical output in the primary motor cortex of the rat.

Application of a GABA (gamma-aminobutyric acid) type A receptor antagonist through a microdialysis probe into the forelimb primary motor cortex (MI) of ketamine anesthetized rats induced the appearance of paroxysmal field potentials recorded in the supragranular layers of the MI and concomitant electromyographic (EMG) activity in the contralateral forelimb. Application of a nonNMDA (N-methyl-D-aspartate) glutamate receptor antagonist in conjunction with the GABA type A receptor antagonist completely blocked the paroxysmal field potentials and the EMG activity of the contralateral forelimb, while a NMDA receptor antagonist had no effect. The results indicate that the spread of activity within the primary motor cortex and the motor cortex output are mediated by nonNMDA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Comparative study of the EEG profile of neuroleptics selective for D-1 or D-2 dopamine receptors in the rabbit.

The neuroleptics SCH 23390 and raclopride, which interact selectively with either D-1 or D-2 dopamine receptor, were studied for their effects on electroencephalographic (EEG) activity in the rabbit. Haloperidol (0.3 and 1 mg/kg intravenously, i.v.), which was used for comparison, induced synchronization of the cortical EEG activity. Spectral EEG analysis showed increase of power in the whole frequency range (0.1-38.5 Hz) and in all frequency bands in the cortex, whereas a slight decrease of slow and fast theta activity (3.7-7.2 and 7.2-12.2 Hz) was observed in the hippocampus. Animals appeared sedated and arousal response to somatosensory stimuli was markedly inhibited. SCH 23390 (0.03 and 0.3 mg/kg i.v.) induced periods of cortical synchronization and changes of spectral power qualitatively similar to those accompanying haloperidol administration. The drug slightly reduced the duration of arousal elicited by stimuli. Raclopride (1 and 3 mg/kg i.v.) induced weak EEG changes and little effect on arousal response to stimulation. There was an increase of slow wave activity which was particularly evident in the hippocampus. The data indicate that, although to a lesser degree, the D-1 receptor antagonist SCH 23390 induced EEG effects similar to those of haloperidol, whereas blockade of D-2 receptors by raclopride resulted in different patterns of EEG activity.

Animals↗

[Spatial synchronization of cortical electrical activity at different stages of visual set in preschool children].

Changes in the alpha-rhythm synchronization were revealed at different stages of cognitive visual set in 5- to 7-year-old children. We found a clear-cut correlation of these changes with set plasticity. In children with a plastic set, the EEG synchronization between the frontal and other brain regions substantially increased in the period of set-shifting (the actualization stage). At the set extinction stage, after set-shifting has already taken place, the EEG-synchronization becomes minimal. On the contrary, in children who formed a rigid set, EEG coherence considerably increases at the set extinction stage. This finding suggests that the rigid set still affects the cognitive activity even after (judging from oral reports) the set shift has been completed. The age-related differences in cognitive set formation clearly correlate with the time course of the EEG synchronization between the frontal and other brain regions. We think that the ability to form a plastic visual set depends on the frontal cortex maturation, which occurs at the age of 6-7 years, and its age-related effect on the brain cognitive functions.

Age Factors↗

Intersubject synchronization of cortical activity during natural vision.

To what extent do all brains work alike during natural conditions? We explored this question by letting five subjects freely view half an hour of a popular movie while undergoing functional brain imaging. Applying an unbiased analysis in which spatiotemporal activity patterns in one brain were used to "model" activity in another brain, we found a striking level of voxel-by-voxel synchronization between individuals, not only in primary and secondary visual and auditory areas but also in association cortices. The results reveal a surprising tendency of individual brains to "tick collectively" during natural vision. The intersubject synchronization consisted of a widespread cortical activation pattern correlated with emotionally arousing scenes and regionally selective components. The characteristics of these activations were revealed with the use of an open-ended "reverse-correlation" approach, which inverts the conventional analysis by letting the brain signals themselves "pick up" the optimal stimuli for each specialized cortical area.

Adult↗