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Background In the procedure of thalamotomy, we mark the targets by thalamic 13−27-Hz β-band and 3−7-Hz τ-range hyperactivities as representing parkinsonian rigidity and tremor, respectively. Aim We tested the validity of these thalamic markers in surgically treated non-parkinsonian patients with tremor of complicated pathophysiology. Methods As the cases with tremor, but no thalamic τ-range hyperactivities, we selected four of the 23 previously studied non-parkinsonian patients; examined the shoulder, neck, face and limb electromyograms, brain local field potentials, and multiple unit spikes; and rated the local field potentials in the bands of 3–7, 7–13, 13–27 and 27–80 Hz. Results Tremor rated as moderate in the present study was postural, kinetic, intentional, ballistic, or myoclonic, or of some combined nature with irregular rhythms at variable frequencies widely ranging in 1–13 Hz. Tremor accompanied motor hyperactivities and thalamic β-band hyperactivities, but not τ-range activities. The β-band hyperactivities and high neural noise occurred in the caudate nucleus, thalamic ventroanterior nucleus, nucleus ventralis lateralis and nucleus ventralis intermedius. The thalamic β-band hyperactivities were not accompanied by rigidity in three of the patients. The four patients were thus atypical when compared with the other non-parkinsonian and parkinsonian patients. Yet, thalamotomy alleviated tremor and concurrent motor hyperactivities. Conclusion Non-parkinsonian tremor in the four patients was related to β-band hyperactivities, and elevating neural noise in wide regions of the basal ganglia and thalamus. Thalamotomy was effective by eventually abolishing ventralis lateralis with β-band hyperactivities and high noise that was involved as a part of the widely distributed pathophysiology of these patients.

Background Parkinsonian thalamic 13- to 27-Hz (β-band) and 3- to 7-Hz (τ-range) hyperactivity is linked to rigidity and tremor, respectively, but not to bradykinesia. Aim To clarify the contributions of different types of thalamic activity to the progression of parkinsonian symptoms, we modeled a neural converter that translates thalamic activity into symptoms and examined its input-output relationship. Methods We scored pre- and postoperative rigidity, tremor, and bradykinesia as well as case-representative τ-range (Vτ) and β-band (Vβ) activity in 170 patients with Parkinson's disease. Results The relationship between abolished rigidity (dR) and Vβ was described by a hysteresis curve, which was simulated by two parabolas relating dR and Vβ to preoperative rigidity (preR) using the calculated time lag corresponding to 1.5 preR grades. The abolished tremor was linearly related to Vτ. The partly abolished bradykinesia was related to Vβ by hysteresis. Hysteresis in the dR-to-Vβ relationship was observed as a result of 11 patients with preR scores of 4. Their brain activity was generally low and similar to that of patients without rigidity. Conclusion In contrast to the direct correlation between Vτ and tremor, Vβ caused rigidity and, in part, bradykinesia via time-consuming processes, as demonstrated by the delayed parabola model. Patients with the severest rigidity showed a loss of thalamic activity and the spread of pathophysiological abnormalities in the neural circuitry beyond the thalamus with progressive age.

Background We monitor brain activities in thalamotomy for Parkinson's disease by a bipolar concentric microelectrode. Aim The present study aimed to standardize the quantitative monitoring for targeting and for pathophysiological analysis. Methods To show the process of data analysis, we selected 20 patients who gave informed consent for thalamotomy. The cases were divided into group I with rigidity, but no tremor (n = 10), and the group II with rigidity and tremor (n = 10). Most patients suffered from bradykinesia. We monitored the electromyograms of the neck and limb muscles. Brain activities were sampled as the electrode passed through the caudate and thalamic nuclei, divided into filtered local field potentials and multiple unit spikes, and rated at different depths by the summed periods in percent occupied by the component wavelets of field potentials at 3–7, 7–13, 13–27 and 27–80 Hz. Results Analysis was summarized by the depth distribution histograms of dominant wavelet compositions. The 13–27-Hz activities were exaggerated in the caudate, thalamic ventroanterior and ventrolateral nuclei. The 3–7-Hz activities time-locked with tremor were exaggerated in the nucleus ventralis intermedius. Group I cases showed little 3–7-Hz activities. Thermolesion in the thalamus with those highly-rated activities alleviated tremor and rigidity, but spared most bradykinesia. Conclusion The standardized analysis suggests that the thalamic 3–7-Hz and 13–27-Hz activities serve as the quantitative markers of pathophysiology representing tremor and rigidity, respectively.

Background Parkinsonian rigidity is alleviated by thalamotomy targeting the thalamic nucleus ventralis lateralis. Detecting there the exaggerated 13–27-Hz β-band activities, we hypothesized that these activities centrally drove rigidity. Aim To test this hypothesis, we examined the temporal relationships of rigidity with β-band activities. Methods In 20 patients with Parkinson's disease, we monitored the thalamic local field potentials and multiple unit spikes with the electromyograms of neck and limb muscles. Results The resting state of muscles with exaggerated tonic discharges in electromyograms was regarded to represent rigidity. The compound muscle spikes as such were accompanied by or synchronized with the thalamic β-band activities when the thalamic recording sites somatotopically met the muscles of interest. The β-band activities consisted of the negative-going deflection of local field potentials and negativity-dominant multiple unit spikes. The β-band local field potentials led to the muscle spikes in spontaneous initiation and development of rigidity, as well as in the cyclic sequence of β-band activities and electromyograms. The paired β-band local field potentials and muscle spikes were moderately correlated in amplitude. During the observation, the grade of rigidity spontaneously fluctuated. Accordingly, the phase coincidence of β-band local field potentials and muscle spikes occurred contingently. When the β-band and tremor-locked 3–7-Hz τ-range activities coexisted at the recording site, different groups of thalamic neurons led to rigidity and tremor, respectively, as their peripheral outcomes. Conclusion The results suggest that the thalamic β-band hyperactivities contingently drive rigidity in support for the central origin hypothesis of rigidity.

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.

We investigated the long-lasting effects of mechanical vibratory stimulation of the skin on the excitability of feline cortical neurons in the forelimb areas of the primary (SI) and secondary (SII) somatosensory cortices. Conditioning mechanical stimuli were 300 bursts of 10 pulses at 200 Hz delivered with a 10-s interburst interval from a mechanical stimulator. Test field potentials and unit discharges were evoked by electrical stimulation to the ventral posterolateral thalamic nucleus (VPL) or by single mechanical stimuli applied to the skin. In SII, the mechanical burst stimulation to the skin increased the amplitudes of field potentials and the frequency of unit discharges elicited by single mechanical stimuli applied to the skin. The vibratory conditioning stimulus also produced a similar potentiation of the VPL-evoked field potentials (126-139% increase in amplitude, P0.05) with an associated increase in firing rates of extracellularly recorded neuronal activity (117%, P0.001). These potentiations persisted through the entire experimental period of 120 min. The translaminar current source density analysis calculated from the VPL-evoked field potentials increased to 127% of the control value (P0.01). In contrast, in SI we observed no significant changes in the field potential amplitudes or in the currents generated in superficial layers (91-117%). Taken together with the previous finding that tetanic electrical stimulation of VPL induces long-lasting potentiation of the VPL-evoked cortical responses in SII but not of those in SI, the present results suggest that SII has a large capacity for the rapid functional plasticity involved in the learning that occurs during repeated tactile experiences.

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.

Since the discovery of the gamma system by Leksell11), its role on voluntary muscular contraction has been emphasized by many workers, 1-7, 10, 14). The papers reported by Matthews and Rushworth on the selective blocking of small motor fibers by procaine12, 13) presented the possibility to study their defect symptoms experimentally produced on human subjects. In the present paper the blocking effect of gamma fibers on voluntary contraction was studied by mathematical analysis of the discharge pattern of a single neuromuscular unit (NMU) and EMG wave form. In addition, the same analysis was applied to muscles of myasthenia gravis and its motor symptoms were discussed from the view point of the gamma activity.

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.