There is growing evidence that Parkinson's disease (PD) is associated with pathological synch... more There is growing evidence that Parkinson's disease (PD) is associated with pathological synchronous oscillatory activity in the basal ganglia. These synchronized oscillations primarily occur in the 11–30 Hz range, the so-called beta band. Studies of local field potential activity in the subthalamic nucleus (STN) of PD patients suggest that exaggerated beta band oscillatory activity can disrupt function and, in particular, may
Deep brain stimulation (DBS) has been playing an increasing role in the treatment of various move... more Deep brain stimulation (DBS) has been playing an increasing role in the treatment of various movement disorders with the most common being Parkinson’s disease (PD). Currently, the preferred target for treating PD motor symptoms is the subthalamic nucleus (STN). Microelectrode recordings are frequently used to aid in the determination of the optimal target for implanting the DBS electrode. Changes in
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2000
It has been hypothesized that in Parkinson's disease (PD) there is increased synchronization ... more It has been hypothesized that in Parkinson's disease (PD) there is increased synchronization of neuronal firing in the basal ganglia. This study examines the discharge activity of 121 pairs of subthalamic nucleus (STN) neurons in nine PD patients undergoing functional stereotactic mapping. Four patients had a previous pallidotomy. A double microelectrode setup was used to simultaneously record from two neurons separated by distances as small as 250 micrometer. In the six patients who had limb tremor during the recording session (n = 76 pairs), the discharge pattern of 12 pairs of tremor cells (TCs) was found to be coherent at the frequency of the limb tremor. Both in-phase and out-of-phase relationships were observed between TCs. Interestingly, in these six patients, 63/129 single neurons displayed 15-30 Hz oscillations, whereas 36/76 pairs were coherent in this frequency range. Although the oscillatory frequencies were variable between patients, they were highly clustered withi...
A new method was developed to aid in the localization of the optimal site for a permanent lesion ... more A new method was developed to aid in the localization of the optimal site for a permanent lesion in movement disorder patients undergoing stereotactic thalamotomy. The method involved making small injections of a local anesthetic into the thalamus, which was also useful in assessing any possible side effects that could potentially arise from the lesion. Initial results indicate that 0.5 to 2-microliters injections of 2% lidocaine at appropriate sites in the thalamic ventrocaudal or ventrointermedius nucleus can produce a temporary marked suppression of tremor. In most cases the lidocaine induced effects mimicked those produced by high frequency electrical stimulation delivered to the same site. However, lidocaine had no effect at some sites where stimulation arrested tremor. This technique promises to be useful not only in the treatment of motor disorder patients but also in other cases where functional localization prior to lesioning is desirable.
Increased afferent input may alter receptive field sizes, properties and somatotopographic repres... more Increased afferent input may alter receptive field sizes, properties and somatotopographic representation in the cortex. Changes in the motor thalamus may also occur as a result of altered afferent input. Such plasticity has been implicated in both sensory and movement disorders. Using tremor as a model of augmented afferent input to kinaesthetic/deep neurons representing the shaking limbs, we studied the representation and properties of these neurons in human thalamus in patients with resting tremor (RestTr) from Parkinson's disease, patients with action- or posture-induced tremor (ActionTr), and patients without tremor (NoTr). Data were collected during stereotactic thalamotomy or insertion of deep brain stimulators for relief of pain or movement disorder. Using microelectrode recording, 58 kinaesthetic neurons responding to wrist and/or elbow movement were studied by mapping the receptive field, carefully isolating each joint during testing. There were no significant differen...
Dopaminergic agents reverse parkinsonism but commonly induce dyskinesia in patients with Parkinso... more Dopaminergic agents reverse parkinsonism but commonly induce dyskinesia in patients with Parkinson's disease (PD) on long-term levodopa therapy. The aim of this study was to determine the neurophysiologic correlates of the amelioration of parkinsonism and the involuntary movements produced by the dopamine agonist apomorphine. Seventeen PD patients were given apomorphine (2-6 mg) before surgery. Neural activity was recorded for individual neurons and for populations of neurons before and after apomorphine. Both internal (GPi) and external (GPe) segments of the globus pallidus were sampled in patients undergoing pallidal surgery. The subthalamic nucleus (STN) was sampled in STN surgery patients. Results suggest that dopaminergic agents act by decreasing GPi and STN activity, and increasing GPe activity, and that drug-induced dyskinesias results from a large reduction in GPi firing.
Thalamic neurons are known to switch their firing from a tonic pattern during wakefulness to a bu... more Thalamic neurons are known to switch their firing from a tonic pattern during wakefulness to a bursting pattern during sleep. Several studies have described the existence of bursting activity in awake chronic pain patients and have suggested that this activity is abnormal and may be related to their pain. However, we have frequently observed bursting activity in awake non-pain patients suggesting that there may not be a causal relationship between thalamic bursting activity and chronic pain. To examine this issue more rigorously we compared the incidence and pattern of bursting activity of lateral thalamic neurons of both pain and non-pain patients in a state of wakefulness. Recordings were obtained from lateral thalamic areas of different groups of patients (n = 91) suffering from pain disorders (e.g. anaesthesia dolorosa, phantom limb pain, trigeminal neuralgia, post-stroke pain) and motor disorders (e.g. Parkinson's disease, essential tremor) during stereotactic surgical proc...
The neural pathways subserving the sensation of temperature are virtually unknown. However, recen... more The neural pathways subserving the sensation of temperature are virtually unknown. However, recent findings in the monkey suggest that the sensation of cold may be mediated by an ascending pathway relaying in the posterior part of the thalamic ventromedial nucleus (VMpo). To test this hypothesis we examined the responses of neurons to thermal stimulation of the skin and determined the perceptual effects of microstimulation in the VMpo region in awake patients undergoing functional stereotactic surgery. In 16 patients, microstimulation in the VMpo region evoked cold sensations in a circumscribed body part. Furthermore, at some of these sites thalamic neurons were found that responded to innocuous cooling of the skin area corresponding to the stimulation-evoked cold sensations. These data provide the first direct demonstration of a pathway mediating cold sensation and its location in the human thalamus.
Experimental studies indicate that deafferentation results in reorganization of the somatosensory... more Experimental studies indicate that deafferentation results in reorganization of the somatosensory map at various levels of the CNS, such that the representation of a body part adjacent to a region that is denervated expands into the deafferented area. Recent data suggest that in the human this occurs at the cortical level, but subcortical structures have not been systematically investigated. To test the hypothesis that the human thalamus is capable of significant reorganization as a result of changes in afferent input, microelectrode recording and stimulating techniques were used to define thalamic somatotopy in 61 patients undergoing stereotactic procedures. Five groups were compared: those with pain in the deafferented body part, face (n = 9), arm/hand (n = 4), leg/foot (n = 8) and hemibody (n = 5) and those with neither pain nor deafferentation, i.e., movement disorder (n = 24). Trunk representation, as determined from receptive fields, was significantly larger in patients with l...
Electroencephalography and clinical neurophysiology, 1986
Recordings were performed in the thalamus of 13 patients suffering from either abnormal movements... more Recordings were performed in the thalamus of 13 patients suffering from either abnormal movements or intractable pain, with the aim of delimiting the region to be destroyed or stimulated in order to diminish the syndrome. In 11 of these patients averaged evoked potentials were recorded simultaneously from the scalp and specific thalamus (VP) hand area levels following median nerve stimulation. These recordings were done during the operation or afterwards when an electrode was left in place for a program of stimulation. The latencies of onsets and peaks on the scalp 'P15' were compared with those of the VP wave; a clear correspondence was found. Moreover, when increased stimulation was used, both waves began to develop in parallel. Thus in the contralateral 'P15' a component exists due to the field produced by the thalamic response. To explain the presence of an ipsilateral scalp 'P15' wave, we propose that a second wave having the same latency and a slightly ...
Neurons in the lateral thalamus of a patient undergoing stereotactic surgery were found to fire i... more Neurons in the lateral thalamus of a patient undergoing stereotactic surgery were found to fire in a characteristic bursting pattern only when the patient was asleep. These novel observations are consistent with animal studies in which the tonic firing pattern of thalamic neurons during wakefulness changes to a bursting pattern during slow-wave sleep.
There is growing evidence that Parkinson's disease (PD) is associated with pathological synch... more There is growing evidence that Parkinson's disease (PD) is associated with pathological synchronous oscillatory activity in the basal ganglia. These synchronized oscillations primarily occur in the 11–30 Hz range, the so-called beta band. Studies of local field potential activity in the subthalamic nucleus (STN) of PD patients suggest that exaggerated beta band oscillatory activity can disrupt function and, in particular, may
Deep brain stimulation (DBS) has been playing an increasing role in the treatment of various move... more Deep brain stimulation (DBS) has been playing an increasing role in the treatment of various movement disorders with the most common being Parkinson’s disease (PD). Currently, the preferred target for treating PD motor symptoms is the subthalamic nucleus (STN). Microelectrode recordings are frequently used to aid in the determination of the optimal target for implanting the DBS electrode. Changes in
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2000
It has been hypothesized that in Parkinson's disease (PD) there is increased synchronization ... more It has been hypothesized that in Parkinson's disease (PD) there is increased synchronization of neuronal firing in the basal ganglia. This study examines the discharge activity of 121 pairs of subthalamic nucleus (STN) neurons in nine PD patients undergoing functional stereotactic mapping. Four patients had a previous pallidotomy. A double microelectrode setup was used to simultaneously record from two neurons separated by distances as small as 250 micrometer. In the six patients who had limb tremor during the recording session (n = 76 pairs), the discharge pattern of 12 pairs of tremor cells (TCs) was found to be coherent at the frequency of the limb tremor. Both in-phase and out-of-phase relationships were observed between TCs. Interestingly, in these six patients, 63/129 single neurons displayed 15-30 Hz oscillations, whereas 36/76 pairs were coherent in this frequency range. Although the oscillatory frequencies were variable between patients, they were highly clustered withi...
A new method was developed to aid in the localization of the optimal site for a permanent lesion ... more A new method was developed to aid in the localization of the optimal site for a permanent lesion in movement disorder patients undergoing stereotactic thalamotomy. The method involved making small injections of a local anesthetic into the thalamus, which was also useful in assessing any possible side effects that could potentially arise from the lesion. Initial results indicate that 0.5 to 2-microliters injections of 2% lidocaine at appropriate sites in the thalamic ventrocaudal or ventrointermedius nucleus can produce a temporary marked suppression of tremor. In most cases the lidocaine induced effects mimicked those produced by high frequency electrical stimulation delivered to the same site. However, lidocaine had no effect at some sites where stimulation arrested tremor. This technique promises to be useful not only in the treatment of motor disorder patients but also in other cases where functional localization prior to lesioning is desirable.
Increased afferent input may alter receptive field sizes, properties and somatotopographic repres... more Increased afferent input may alter receptive field sizes, properties and somatotopographic representation in the cortex. Changes in the motor thalamus may also occur as a result of altered afferent input. Such plasticity has been implicated in both sensory and movement disorders. Using tremor as a model of augmented afferent input to kinaesthetic/deep neurons representing the shaking limbs, we studied the representation and properties of these neurons in human thalamus in patients with resting tremor (RestTr) from Parkinson's disease, patients with action- or posture-induced tremor (ActionTr), and patients without tremor (NoTr). Data were collected during stereotactic thalamotomy or insertion of deep brain stimulators for relief of pain or movement disorder. Using microelectrode recording, 58 kinaesthetic neurons responding to wrist and/or elbow movement were studied by mapping the receptive field, carefully isolating each joint during testing. There were no significant differen...
Dopaminergic agents reverse parkinsonism but commonly induce dyskinesia in patients with Parkinso... more Dopaminergic agents reverse parkinsonism but commonly induce dyskinesia in patients with Parkinson's disease (PD) on long-term levodopa therapy. The aim of this study was to determine the neurophysiologic correlates of the amelioration of parkinsonism and the involuntary movements produced by the dopamine agonist apomorphine. Seventeen PD patients were given apomorphine (2-6 mg) before surgery. Neural activity was recorded for individual neurons and for populations of neurons before and after apomorphine. Both internal (GPi) and external (GPe) segments of the globus pallidus were sampled in patients undergoing pallidal surgery. The subthalamic nucleus (STN) was sampled in STN surgery patients. Results suggest that dopaminergic agents act by decreasing GPi and STN activity, and increasing GPe activity, and that drug-induced dyskinesias results from a large reduction in GPi firing.
Thalamic neurons are known to switch their firing from a tonic pattern during wakefulness to a bu... more Thalamic neurons are known to switch their firing from a tonic pattern during wakefulness to a bursting pattern during sleep. Several studies have described the existence of bursting activity in awake chronic pain patients and have suggested that this activity is abnormal and may be related to their pain. However, we have frequently observed bursting activity in awake non-pain patients suggesting that there may not be a causal relationship between thalamic bursting activity and chronic pain. To examine this issue more rigorously we compared the incidence and pattern of bursting activity of lateral thalamic neurons of both pain and non-pain patients in a state of wakefulness. Recordings were obtained from lateral thalamic areas of different groups of patients (n = 91) suffering from pain disorders (e.g. anaesthesia dolorosa, phantom limb pain, trigeminal neuralgia, post-stroke pain) and motor disorders (e.g. Parkinson's disease, essential tremor) during stereotactic surgical proc...
The neural pathways subserving the sensation of temperature are virtually unknown. However, recen... more The neural pathways subserving the sensation of temperature are virtually unknown. However, recent findings in the monkey suggest that the sensation of cold may be mediated by an ascending pathway relaying in the posterior part of the thalamic ventromedial nucleus (VMpo). To test this hypothesis we examined the responses of neurons to thermal stimulation of the skin and determined the perceptual effects of microstimulation in the VMpo region in awake patients undergoing functional stereotactic surgery. In 16 patients, microstimulation in the VMpo region evoked cold sensations in a circumscribed body part. Furthermore, at some of these sites thalamic neurons were found that responded to innocuous cooling of the skin area corresponding to the stimulation-evoked cold sensations. These data provide the first direct demonstration of a pathway mediating cold sensation and its location in the human thalamus.
Experimental studies indicate that deafferentation results in reorganization of the somatosensory... more Experimental studies indicate that deafferentation results in reorganization of the somatosensory map at various levels of the CNS, such that the representation of a body part adjacent to a region that is denervated expands into the deafferented area. Recent data suggest that in the human this occurs at the cortical level, but subcortical structures have not been systematically investigated. To test the hypothesis that the human thalamus is capable of significant reorganization as a result of changes in afferent input, microelectrode recording and stimulating techniques were used to define thalamic somatotopy in 61 patients undergoing stereotactic procedures. Five groups were compared: those with pain in the deafferented body part, face (n = 9), arm/hand (n = 4), leg/foot (n = 8) and hemibody (n = 5) and those with neither pain nor deafferentation, i.e., movement disorder (n = 24). Trunk representation, as determined from receptive fields, was significantly larger in patients with l...
Electroencephalography and clinical neurophysiology, 1986
Recordings were performed in the thalamus of 13 patients suffering from either abnormal movements... more Recordings were performed in the thalamus of 13 patients suffering from either abnormal movements or intractable pain, with the aim of delimiting the region to be destroyed or stimulated in order to diminish the syndrome. In 11 of these patients averaged evoked potentials were recorded simultaneously from the scalp and specific thalamus (VP) hand area levels following median nerve stimulation. These recordings were done during the operation or afterwards when an electrode was left in place for a program of stimulation. The latencies of onsets and peaks on the scalp 'P15' were compared with those of the VP wave; a clear correspondence was found. Moreover, when increased stimulation was used, both waves began to develop in parallel. Thus in the contralateral 'P15' a component exists due to the field produced by the thalamic response. To explain the presence of an ipsilateral scalp 'P15' wave, we propose that a second wave having the same latency and a slightly ...
Neurons in the lateral thalamus of a patient undergoing stereotactic surgery were found to fire i... more Neurons in the lateral thalamus of a patient undergoing stereotactic surgery were found to fire in a characteristic bursting pattern only when the patient was asleep. These novel observations are consistent with animal studies in which the tonic firing pattern of thalamic neurons during wakefulness changes to a bursting pattern during slow-wave sleep.
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