[Pain---neurophysiological basis and neurophysiologically founded methods of treatment].
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Thirty-three styrene exposed workers from three different industrial sites were examined with electroencephalography and motor and sensory neurography. The three groups had respective styrene exposures of clearly above the threshold limit value (50 ppm), at about this level, and clearly below it. The neurophysiological results were compared with those of a group of normal controls and a group of 17 patients judged to suffer from sequelae after long-term heavy exposure to organic solvents (mainly painters). Ten subjects in the styrene group presented signs of a mild sensory neuropathy with polyphasic sensory responses of a low amplitude. The same pattern was commonly found among the reference group heavily exposed to solvents. The ten subjects in the styrene group with mild polyneuropathy had a significantly higher age and significantly heavier styrene exposure than the rest of the group. Age difference could not explain the difference in the neurophysiological parameters, and therefore the contributing role of styrene exposure has to be considered. The electroencephalographic analysis showed no changes of the dominant alpha frequency. An increased amount of diffuse slow activity was seen in many of the heavily exposed mixed-solvent cases and was seen in some of the styrene-exposed cases without a clear relation to degree of exposure. An increased occurrence of fast activity in central and precentral areas of the brain was found in the styrene group, as well as in the mixed-solvent group. This pilot study indicates that the same type of neurophysiological changes from the strictly normal are seen among workers exposed to styrene as those found among a group of patients judged to suffer from sequelae after chronic exposure to various organic solvents. The neurophysiological "profile" is (a) sensory nerve responses with low amplitude and long duration, (b) somewhat low sensory conduction velocities, (c) close to normal motor neurographic findings, and (d) an increased amount of fast activity in central and precentral regions in the electroencephalogram in combination with normal occipital alpha activity.
Neurophysiological and histological studies have been performed on the sympathetic nervous system of cats poisoned with acrylamide. The neurophysiological studies indicate that the large and small diameter myelinated fibres are damaged in the sympathetic nervous system in association with damage to the fibres of the peripheral nervous system. Quantative histological studies confirmed and extended the neurophysiological findings; there was a loss of myelinated fibres of all diameters from the sympathetic, parasympathetic and peripheral nervous system.
Treatment-resistant depression (TRD) affects approximately 30% of patients with major depressive disorder. Stanford Neuromodulation Therapy (SNT), a high-dose intermittent theta-burst transcranial magnetic stimulation protocol, produces rapid antidepressant effects, but its neurophysiological mechanisms remain unclear. Here, we used longitudinal TMS-EEG to characterize the progressive neurophysiological changes induced by SNT, assess their site-specificity, and explore whether baseline neural markers are associated with clinical response. We conducted a double-blind, randomized, sham-controlled trial at Stanford University (2017-2018; analysis August 2024-October 2025) in 24 TMS-naïve participants with TRD (Montgomery-Åsberg Depression Rating Scale ≥20; ≥1 failed antidepressant trial). Participants were randomized to active (n = 12) or sham (n = 12) SNT, consisting of 10 sessions per day over 5 consecutive days targeting the left dorsolateral prefrontal cortex (90,000 pulses). TMS-EEG was acquired at two baseline sessions, before and after each treatment session, and at 1-month follow-up (14 TMS-EEG sessions in total). Active SNT progressively reduced cortical excitability at the treatment site, with significant decreases by day 3 in the early window component (-27.9%; P < 0.01), while no changes were observed at the vertex control site. Site-specific comparisons confirmed early window reductions only at the left dorsolateral prefrontal cortex (t₂₂ = -3.82; P < 0.001). SNT also selectively decreased estimated medial prefrontal source activity consistent with the subgenual anterior cingulate cortex (sgACC) across sessions (F₁₃,₂₂₂ = 4.93; P < 0.001), with effects persisting at 1-month follow-up. In an exploratory analysis in the active group (n = 12), higher baseline estimated sgACC source activity was associated with greater clinical improvement (r = -0.67; P = 0.023); although promising, the latter preliminary finding requires replication in larger, adequately powered samples before predictive utility can be established. These findings indicate that SNT induces progressive, site-specific cortical modulation and selective downstream effects on estimated sgACC source activity. Early cortical excitability changes represent candidate neurophysiological markers of SNT response, while the observed association between baseline sgACC activity and clinical outcome, while preliminary, motivates prospective investigation of subcortical source activity as a potential predictor of treatment response in larger trials. ClinicalTrials.gov Identifier: NCT03068715.
Rana pipiens with skin dorosoventrally reversed can respond to stimulation of the back with forelimb wipes to the belly and to stimulation of the belly with hindlimb wipes to the back. These "misdirected wiping responses" have been explained in terms of two alternative hypotheses of nerve regeneration: nerve respecification or selective reinnervation. Experimental behavioral and neurophysiological experiments reported here support the selective reinnervation hypothesis. Severing ventral nerves, which normally innervate the belly, greatly reduced the percentage of misdirected responses on stimulation of belly skin grafted to the back, while severing dorsal nerves, which normally innervate the back, increased the percentage of misdirected responses elicited under the same circumstances. Moreover, neurophysiological recordings of grafted animals showed three effects of skin grafting on nerve distributions: (i) termination of dorsal and ventral nerve receptive field at graft edges; (ii) overlap of nonadjacent ventral nerve receptive fields; and (iii) dorsal coursing of ventral nerves to reinnervate target belly skin displaced to the back. These neurophysiological observations, and particularly the third effect, also support selective reinnervation as the mechanism of nerve regeneration in skin-grafted Rana pipiens.
Neurophysiological and behavioral measures were obtained from 32 senescent (28--34 mo) and 32 mature adult (10--16 mo) rats. Extracellularly recorded synaptic responses were obtained from electrodes chronically implanted in the fascia dentata and perforant path. The rats were first tested on a circular platform, which favored the use of spatial cues for its solution, and the senescent rats were shown to exhibit poorer memory for the rewarded place. When granule cell synaptic responses were recorded after a single session of very brief high-frequency stimulation, the amount of elevation and time course of decline were equivalent between age groups. Af ter three repetitions, however, the young rats maintained the increased synaptic strength for at least 14 days, whereas the old rats declined after the first session. The amount of synaptic enhancement was statistically correlated with the ability to perform the circular platform task both within and between groups. Furthermore, the aftereffects of the high-frequency stimulation selectively impaired the old rats' spontaneous alternation behavior on a T-maze. Certain other neurophysiological and electroencephalographic measures did not distinguish between age groups. The results are discussed in terms of the synaptic theory of memory formation and of their relevance to the aging process.
The author provides a brief primer of the biologic processes in the brain that produce affect and implement communication. These neuroanatomic and neurophysiologic processes are presented in broad configuration rather than in detail and as distributive systems rather than just as localized mechanisms. The basic viewpoint is that of a continuum between the biologic processes within the brain and their manifestation as behavioral phenomena expressed in, and visible to, the culture. The primary focus is not clinical but on neuroanatomy and neurophysiology as basic medical sciences for psychiatry.
The early statements that the EEG alone could correctly be used for the assessment of gestational age (cf., among others, Dreyfus-Brisac, 1964; Parmelee et al., 1968; and Nolte et al., 1969), even in pathological babies, need some restrictive qualifications. Likewise, the more recent statements that certain neurophysiological parameters, including nerve conduction velocity and basic EEG patterns are independent not only of gestational age and body weight, but also of various abnormal factors in the pre- and perinatal periods, appear also too rigid, at least as regards the EEG and the other parameters used in this study. As a matter of fact, some authors who had adhered rather strictly to these concepts have later on presented evidence suggesting some deviations in bioelectric brain maturation in some cases, as for example, in small-for-date newborns of toxemic mothers (Schulte et al., 1972). When more exact quantification by coding techniques was applied (Parmelee et al., 1968), the conclusion was also reached that extrauterine and intrauterine development of bioelectric brain activity developed according to the conceptional age, regardless of variable extrauterine experience, although it was recognized that other categories of behavioral and neurophysiological activities, for example, Moro reflex, states stability, crying, sucking, scores, etc., are more labile to environmental and pathological factors (Prechtl et al., 1972; Michaelis et al., 1973).
Neurophysiological studies have yielded new insights into sleep disorders. Neurophysiological processes play a major roll in sleep disorders in children. Learning theory can be used for the explanation and treatment of sleeping disorders.
After a discussion concerning the semantic contents of terms such as: emotions, pulsions, motivations, as much from the physiological as from the psychological point of view as well as with regard to the role of the processes of memory and learning in their elaboration, the neurophysiological plane of fundamental behaviour patterns is approached. The role of the dorsomedian amygdala and of the lateral hypothalamus in the processes of behavioural activation as well as that of the septal area, of the hippocampus, of the lateral amygdala, of the ventro-median hypothalamus in the processes of inhibition are recalled. The action upon the environment and the reaction to the environment (conditioned or unconditioned) of this system are studied. Anxiety is considered as resulting from the inhibition of action and its endogenous or exogenous causes, as well as the mechanisms of its disappearance, are examined. The distinction between hypophyso-corticoadrenal alarm reaction and sympatho-adrenergic defence reaction is recalled. Basing himself upon the experimental work of his laboratory, the author shows that in the defence reaction it is necessary to make the distinction between the sympathetic reaction, noradrenergic, brrenergic reaction, medullo-adrenal, controlled by the system of behavioural activation. He shows the interest of such a distinction on the physio-pathological plane. Finally he approaches the biochemical level, that of the neuro-modulators and of their central role. He suggests that the effect alpha of catecholamines and the nicotinic effect of acetylcholine indeed seem to have a direct role in the control of synaptic activity, while the beta effect and the muscarinic effect could have a secondary role through the intermediary of the synthesis of cAMP and cGMP respectively. The second messengers would intervene principally in the neuronal protein synthesis and the long term memory. The work ends with a rapid summary concerning the biochemical and neurophysiological mechanisms of drugs which act upon behaviour patterns. This summary is based on the outline previously elaborated.
Morphology, biochemistry and neurophysiological comparisons with effects of brain-toxic substances. The acute damage of the liver by thioacetamide is characterized neurophysiologically by a far--reached synchronous beginning of cortical and subcortical alteration of activity, a retardation of cortical and subcortical EEG, threshold increase of the EEG--arousal reaction, reductions in amplitude of centrally evoked potentials and increase of acoustically evoked potentials. We impute that according to an acute "toxic" damage of the liver a "membrane hyperpolarisation" results in all or nearly all areas of the brain. A general decrease of excitability of the brain seems consequently plausible. In opposition to this results only activities of the cortex or structures nearby the cortex (areas above the midbrain reticular formation) will be affected by exogenous arterial hyperammoniemia up to 1700 mug/100 ml.
It is a common clinical misconception to regard the spinal micturition reflex center as fundamentally overactive and dependent on cerebral inhibition. Initiation and cessation of micturition is simplistically viewed as a manifestation of voluntary withdrawal and resumption of inhibitory corticospinal "regulation''. This view is in conflict with basic neurophysiologic experimental data. Actually, the organization of the micturition reflex is extremely complex. It is affected by multiple sources of facilitative and inhibitory influence, peripheral as well as central. During the past half century, at least twelve reflexes involved in urine storage and coordinated micturition have been described by various neurologic investigators. In this article the integral reflexes are identified and described. A functional organization of the integral reflexes which includes a modern concept of their role in the physiology of urine storage and micturition is presented. It is implicit that overactivity or functional failure of any one or combination of the integral reflexes may cause a significant disorder of lower urinary tract function.
Within the limits of standard neurophysiologic techniques, we have attempted to redefine laryngeal spasm as distinct from the glottic closure reflex. This distinction is based upon the observation that laryngeal spasm is solely mediated by the superior laryngeal nerve. Stimulation of other afferent nerves, capable of eliciting the glottic closure reflex, produces little adductor after-discharge activity that is characteristic of laryngeal spasm. In this regard, modification of output function from the adductor motoneuron aggregate by means of temporal and spatial summation of sensory input data has been described, and its characteristics further defined in response to varying ventilatory states and barbiturate levels.
Clinical study of three schizophrenic men without known seizure disorders has heuristic implications, pointing to neurophysiological factors in their somesthetic hallucinations: (a) In two instances the body areas involved in such hallucinations (the abdominal cavity and the top of one foot) also happen to be represented side by side on the "map" of the receptive somesthetic areas at the postcentral gyrus. (b) In all three schizophrenic men the occurrence of their somesthetic hallucinations can be conceptualized along the lines of MacKay's (1970) information flow model for perception in general, with some specific modifications, which center around the key roles of sufficient change occurring in two specific aspects of this model. (c) Further conceptualization is suggested within Grey Walter's (1973) testable model of triple association among Conditional, Imperative and Operant Response--albeit mostly in reverse sequence with respect to somesthetic hallucinations under discussion. These schizophrenic men reveal in their past and present experiences a pattern in which the sequence of events is initiated through changes at the efferent side (restriction of voluntary motility), which trigger afferent experiences, albeit hallucinated ones. Practical implications center around the probably salutary role of voluntary motility performed purposefully and at the person's own pace.
Consciousness may be understood as a behavioural state and thus levels of consciousness may be distinguished. But consciousness as we understand it is an experience. Any critical reasoning about it will lead to a dualistic formula. A neurophysiological mechanism may exist for this. In the neocortex various aspects of the world and of the physical and social relationships of the individuum to the world are represented through thalamocortical projection systems. There is no unified representation of the world in any single cortical area. All neocortical outputs feed into action systems of the brain. The synthesis of the distributed cortical representations of the world is thus realized through the action elicited by their combination. The action systems of the midbrain-cerebellum and the basal ganglia feed back into neocortical areas (internal loops). The action itself changes the relationship of the individual to the outside world and thus its representation in the brain (external loops). The role of the basal ganglia in the normal functioning of processes in consciousness and in the synthesis of cortical representations is described, which further emphasizes the intricate connections between motor performance and consciousness. The function of the reticular substance and related structures is seen as a gating mechanism for the (thalmic) access gates to the cortex and thus to mechanisms of conscious experience. The basis for the experience of consciousness is the symbolic representation of the world and of the individual to that individual's brain. This self-representation is based on the linguistic competence of the brain in a broad sense and is therefore possible only for brains with such a competence. The symbolic self-representation is called the reflective loop and its conditons are briefly discussed.
The relation of the cortex, cerebellum, and basal ganglia and their participation in movement disorders is presented. Studies have shown that lesions to the cortex will produce contralateral paralysis while damage to the basal ganglia or cerebellum will result in movement abnormalities. These data provide support for the view that subcortical but not cortical structures initiate the control movement activity. It would appear that the basal ganglia and cerebellum receive signals from the auditory, visual, and somatosensory cortex integrate this information, and relay signals back to the motor cortex, which in turn sends out efferent fibers to the motor neurons of the spinal cord. The electronic and neurophysiological basis of the somatosensory evoked responses (SER) test following peripheral nerve stimulation and sensory recording in human cortex is given. Control values of SER peak to peak latency waveforms from 66 normal volunteers show the practicality of this test. Preliminary results using SER in patients are discussed from clinical case reports. The subjects had mild to marked movement disorders secondary to Parkinson's disease, vascular occlusion, multiple sclerosis, and spino-cerebellar degeneration. The potential of the SER as a clinical and experimental tool in evaluating movement abnormalities and other neuropathological conditions is presented.