Search

Background and Aim Passive and active muscle manipulations modify parkinsonian tremor and rigidity. We hypothesized that these outer maneuvers provoke thalamic 3 to 7-Hz (τ-range) and 13 to 27-Hz (β-band) activities, which in turn act to develop and maintain the symptoms. To test the hypothesis, we examined the temporal and quantitative relationships of the thalamic activities with the symptoms in conditions under the outer maneuvers. Methods In thalamotomy for 20 patients with Parkinson's disease, we monitored thalamic local field potentials and multiple unit spikes with surface electromyograms of neck and limb muscles. Results Tremor is intensified in postural and kinetic modes with higher amplitude and faster frequency than the resting state, and in tremor rhythms on the cogwheel rigidity with accelerated muscle tone. Exaggerated thalamic τ-range activities always led to tremor of those intensified modes. The τ-range activities developed and maintained tremor in keeping a quantitative relationship in amplitude. Both the passive and active muscle manipulations transiently abolished the β-band activities, and then made them relapse to lead to rigidity in a waning and waxing fashion. Because of these changes of β-band activities, the patient's active effort to move or hold postures caused a state in conflict between voluntary and involuntary contractions. Conclusion Together, the results suggest that passively activated peripheral kinesthetic afferents, and actively triggered central motor initiatives act to develop and maintain tremor and rigidity through the thalamic motor nuclei as the crucial relay stations.

1) In the encephale isole cat preparation the cerebral peduncle (CP) and the nucleus ventralis lateralis (VL) of the thalamus were stimulated. Short-latency responses recorded from precruciate cortical neurons consisted of excitatory (EPSP) and inhibitory postsynaptic potentials (IPSP). 2) Laminar distributions of these responses and their latencies were viewed as the spatiotemporal pattern of spread of excitation and inhibition within the cortex in comparison with those obtained by epicortical stimulation (EPICS). 3) In contrast with activities by EPICS spreading downwards from superficial to deep layers, CP recurrent activities spread upwards from deep to middle or superficial layers, and those by VL afferents spread from middle to both superficial and deep layers bidirectionally. 4) These three intracortical routes shared common cell assemblies in that they received convergent EPSPs or IPSPs to various extents from different inputs. The routes for EPICS and VL inputs were overlapped particularly with abundant supply of convergence in spite of their functional difference. Relevant potentiality of the cerebral network in forming plural patterns was discussed.

1. Intracellular potentials were recorded from 164 cells in cat precruciate cortex, and their responses were examined during the phasic and tonic phases of EEG arousal. 2. According to the initial responses corresponding to phasic EEG arousal, these cells were classified into 71 E (excitation), 49 I (inhibition), 38 DF (disfacilitation), and 6 DI (disinhibition) cells. 3. The late responses corresponding to tonic EEG arousal varied among these cells. Thirty-two of the 164 cells were unresponsive. Of the remaining cells, 102 showed excitation, 16 inhibition, 12 disfacilitation, and 2 disinhibition. These cells were retermed +E, +I, +DF, and +DI cells, respectively. 4. +E cells were located at all depths through laminae I to VI, but the majority were found in laminae IIIb-VI. +I cells were between lamina I and the lower half of lamina III (IIIb), and +DF and +DI cells were between lamina I and the upper half of lamina III (IIIa). From these characteristic layer distributions it is postulated that an upward cascade transmission from deep to superficial layers occurs during tonic EEG arousal. 5. Nine types of combinations of the initial and late responses were found: E, I, DF or DI with +E, E or I with +I, E or I with +DF, and I with +DI. To explain these various activity patterns, an 'arousal' circuit model was proposed by combining the downward and upward cascade transmission patterns. The elementary structure of cortical arousal was thus formulated, and discussed from the development aspect of behavior.

1. Changes in the resting potential and the effective membrane resistance were measured in 77 cells in cat precruciate cortex during the transition from cortical slow wave phase to EEG arousal. 2. These 77 neurones were classified into the recipient cells of the following five different actions on the EEG arousal: (1) postsynaptic excitation (E cells), (2) postsynaptic inhbition (I cells), (3) disinhibition (DI cells), (4) disfacilitation (DF cells) and (5) disfacilitation followed by excitation (DF-E cells). 3. The location of E cells ranged from laminae I to V, but the majority was found in lamina II. Most I cells were located in the upper half of lamina III, and a few in lamina V. DF, DI and DF-E cells existed deeply from the lower half of lamina III to laminae V-VI. 4. Slow pyramidal tract (PT) cells (n = 6) all belonged to the E cell group, whereas fast PT cells were divided into the DF (n = 10) and DF-E cell groups (n = 4). 5. It is postulated that the EEG arousal is initiated with a direct excitation of laminae I-II cells, followed by excitation and inhibition to the upper lamina III cells and further processed to laminae III-VI cells with indirect excitation, inhibition, disinhibition and disfacilitation. The model of four vertical transmission relays is proposed to depict the casade pattern of information being processed through the cortex during the EEG arousal.

1. Intracellular recordings were made from 92 neurones in the precruciate cortex of encephale isole and midpontine pretrigeminal preparations of the cat. 2. All but only one of these cells showed appreciable changes in the membrane potential during the transition from the cortical slow wave phase to the EEG arousal occurring spontaneously or induced by stimulating the midbrain reticular formation. Thus, 38 cells were depolarized (D-type cells), 48 cells hyperpolarized (H-type cells) and 5 cells showed an early hyperpolarization and a later depolarization (mixed type). 3. The latency of intracellular responses to reticular stimulation was shorter in the D-type cells than the H-type or mixed-type cells, and shorter for each of the D- and H-types in the cells of the superficial layers than those of the deep layers. 4. The D-type cells were distributed widely through laminae I to V, but the majority was sampled in lamina II. The H-type cells were located in laminae III-VI with the mode at the upper half of lamina III. The mixed-type cells were mostly located in laminge V and VI. 5. Antidromically identified slow pyramidal tract (PT) cells n=9) all belonged to the D-type, and fast PT cells either to the H- (n=11) or the mixed type (n=4). 6. These results suggest that the EEG arousal is a state composed of both excitatory and inhibitory responses of cortical cells which are processed from the superficial to the deep layers.

Lateral spread of activity within the motor cortex was examined by means of analyses of the direct cortical responses (DCRs) and intracellular responses to distant epicortical stimulation (EPICS) using cat encephale isole preparations. DCRs to the EPICS at a distance of 1.5-6.5 mm consisted of initial small positive (Pd) and subsequent negative waves (Nd). The reversal of polarity in depths occurred at 400-550 microns for Pd and at 150-250 microns for Nd as well as for the initial negative wave elicited by near EPICS. Intracellular responses to distant EPICS consisted of excitatory (EPSP) and inhibitory postsynaptic potentials (IPSP), disfacilitation (DF), and disinhibition (DI). Depth distributions of cells with EPSPs at two peaks in laminae II and V-VI, with IPSPs mainly in lamina III, and with DF or DI in laminae V-VI were the same with those by near EPICS. The inhibitory effects of distant EPICS on middle layer cells were much greater than those by near EPICS. No linear relations of the latency of EPSPs or IPSPs to the depth were seen for distant EPICS. Instead, the latency increased in proportion to the lateral distance in EPSPs at a slower rate than in IPSPs compared in superficial and middle layer cells. Several routes for lateral spread of activity were postulated. Most conspicuous are the excitatory route via horizontal axons in lamina I and the inhibitory route via laterally running axons in laminae II-III, which produce overall excitation of superficial layer cells and depression of middle and deep layer cells. Their possible role in phasic cortical arousal was discussed.

In the encephale isole cat preparation the surface of precruciate cortex was electrically stimulated. Intracellular responses underneath the stimulated site were recorded to assess the vertical spread of activities across the cortical layers. 2) To the epicortical stimulation (EPICS) with intensity adjusted to evoke a pure negative wave in the direct cortical response (DCR), only some neurons in relatively superficial layers responded with excitatory postsynaptic potentials (EPSPs). 3) Stimuli intensified to evoke both the negative and subsequent positive waves in DCR produced in all tested cells either EPSPs, inhibitory postsynaptic potentials (IPSPs), or both. Direct or axonal antidromic excitation of the cell was observed only infrequently. 4) Cells with EPSPs distributed through all the layers with two peak populations in laminae II and V-VI. Those with IPSPs were located mainly in the upper half of lamina III with a few in more superficial as well as in deeper layers. Both EPSPs and IPSPs showed mono- or oligosynaptic latencies (0.6-10msec) that tended to become longer in deep than in superficial layers. 5) Some deep layer cells including fast and slow pyramidal tract cells showed slowly rising monosynaptic EPSPs of dendritic origin. 6) Further late responses consisted of EPSPs, IPSPs, disfacilitation (DF), and disinhibition (DI). DF or DI occurred in some deep layer cells. 7) Two modes of vertical spread of activities were postulated : one the cascade transmissions which increased response repertoire toward the depths, and the other the electrotonic spread of EPSPs along dendrites.

1. Intracellular activities of fast pyramidal tract (PT) cells and their family neurones were investigated during the EEG arousal of various degrees in terms of (1) the strength of natural or midbrain reticular stimuli, (2) the length of aroused EEG and (3) the extent of stage shift from EEG synchronization to desynchronization. 2. These cells showed a response pattern of either disfacilitation (DF), disfacilitation followed by excitation (DF + E) or excitation (E). DF and E components in these responses were respectively quantified with their amplitude and incidence, and their relations to the above-listed intensity parameters of EEG arousal were examined. 3. The threshold of eliciting DF response was lower than that for E response to natural and reticular stimuli. On intensifying the parameters of EEG arousal, accompanying increases were observed in E response but not in DF response. Rather, DF response was often masked by E response on application of relatively intense stimuli, or was decreased in a reciprocal manner to the increase of E response in accordance with the degree of EEG arousal. 4. It is postulated that the phasic and tonic phases of EEG arousal manifested, respectively, as the initial DF and late E responses bear different functions, the former representing the cerebral state of a general set on receipt of a novel stimulus, and the latter involving the state of actively responding to the stimulus by encoding its intensity.

1) Intracellular responses during phasic Electroencephalograph (EEG) arousal were recorded from 229 motor cortical neurons in the cat encephale isole preparations. Identified dominant responses were excitatory postsynaptic potentials (EPSPs) in 105 cells (E cells), inhibitory postsynaptic potentials (IPSPs) in 74 cells (I cells), disfacilitation in 48 cells (DF cells), and disinhibition in two cells (DI cells). 2) These responses were comparable with those to near or distant epicortical stimulation (EPICS). Thus, most E cells in phasic arousal were EPSP-dominant in response to near (incidence, 104/105) or distant EPICS (51/54), and only a few of the remaining were IPSP-dominant. About two-thirds of I cells were IPSP-dominant (49/74), and the remaining one-third were EPSP-dominant (25/74) to near EPICS. However, most I cells became IPSP-dominant (45/49) to distant EPICS. 3) DF and DI cells were initially EPSP- or IPSP-dominant to EPICS, but later responsive with DF in DF cells and DI in DI cells, respectively. 4) In the interaction experiments, the initial negative wave in the direct cortical responses (DCRs) or the EPSPs of dendritic origin elicited by near EPICS and the initial positive wave in DCRs to distant EPICS were all reduced during phasic EEG arousal perhaps due to the occlusion effect. 5) Common response repertoire in EEG arousal and epicortical activation may support the earlier proposed cascade transmission model of phasic EEG arousal, in which the spread of neuronal activities occurs vertically from the superficial to deep cortical layers as well as laterally along various layers.