Passing lanes and slow lanes into the nociceptive network of the human brain.
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Biomedical subjects
Publications and source records attributed to Frederick A Lenz.
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Over the past two decades, deep brain stimulation (DBS) has supplanted lesioning techniques for the treatment of movement disorders, and has been shown to be safe and efficacious. The primary therapeutic indications for DBS are essential tremor, dystonia and Parkinson's disease. In the case of Parkinson's disease, DBS is effective for treating the primary symptoms--tremor, bradykinesia and rigidity--as well as the motor complications of drug treatment. Progress has been made in understanding the effects of stimulation at the neuronal level, and this knowledge should eventually improve the effectiveness of this therapy. Preliminary studies also indicate that DBS might be used to treat Tourette's syndrome, obsessive-compulsive disorder, depression and epilepsy. As we will discuss in this review, the success of DBS depends on an appropriate rationale for the procedure, and on collaborations between neurologists and neurosurgeons in defining outcomes.
PURPOSE: To evaluate speech recognition in patients with focal intractable epilepsy and surgical resections in the nondominant (right) hemisphere. METHODS: Speech recognition was tested prospectively, under different listening conditions, in 22 patients with right temporal lobe (11 patients) or extra-temporal lobe epilepsy. All were left-hemisphere dominant for language on preoperative intracarotid sodium amobarbital testing. RESULTS: All patients demonstrated normal auditory recognition of words and environmental sounds before and after surgery. However, when real-world listening conditions were simulated by using acoustically degraded (filtered) words, patients with temporal lobe epilepsy performed significantly worse than patients with frontal or parietooccipital lobe epilepsy before and after surgery (p<0.0001). CONCLUSIONS: Patients with intractable right temporal lobe epilepsy are at risk for speech recognition impairments in real-world listening environments, independent of surgery. The impact of speech recognition difficulties on verbal communication, coupled with the prevalence of adverse listening environments, underscores the importance of testing speech recognition under different listening conditions in patients with intractable right temporal lobe epilepsy.
Lesion or degeneration of the cerebellum can profoundly impair adaptive control of reaching in humans. Computational models have proposed that internal models that help control movements form in the cerebellum and influence planned motor output through the cerebello-thalamo-cortical pathway. However, lesion studies of the cerebellar thalamus have not consistently found impairment in reaching or adaptation of reaching. To elucidate the role of the cerebellar thalamus in humans, we studied a group of essential tremor (ET) patients with deep brain stimulation (DBS) electrodes placed in the cerebellar thalamus. The stimulation can be turned on or off remotely and is thought to reduce tremor by blocking the spread of the pathological output from the cerebellum. We studied the effect of thalamic DBS on the ability to adapt arm movements to novel force fields. Although thalamic DBS resulted in a dramatic and significant reduction of tremor in ET, it also impaired motor adaptation: the larger the stimulation voltage, the greater the reduction in rates of adaptation. We next examined ET patients that had undergone unilateral thalamotomy in the cerebellar thalamus and found that adaptation with the contralateral arm was impaired compared with the ipsilateral arm. Therefore, although both lesion and electrical stimulation of the cerebellar thalamus are highly effective in reducing tremor, they significantly impair the ability of the brain to form internal models of action. Adaptive control of reaching appears to depend on the integrity of the cerebello-thalamo-cortical pathway.
Subdural electrocorticographic (ECoG) recordings in patients undergoing epilepsy surgery have shown that functional activation is associated with event-related broadband gamma activity in a higher frequency range (>70 Hz) than previously studied in human scalp EEG. To investigate the utility of this high gamma activity (HGA) for mapping language cortex, we compared its neuroanatomical distribution with functional maps derived from electrical cortical stimulation (ECS), which remains the gold standard for predicting functional impairment after surgery for epilepsy, tumours or vascular malformations. Thirteen patients had undergone subdural electrode implantation for the surgical management of intractable epilepsy. Subdural ECoG signals were recorded while each patient verbally named sequentially presented line drawings of objects, and estimates of event-related HGA (80-100 Hz) were made at each recording site. Routine clinical ECS mapping used a subset of the same naming stimuli at each cortical site. If ECS disrupted mouth-related motor function, i.e. if it affected the mouth, lips or tongue, naming could not be tested with ECS at the same cortical site. Because naming during ECoG involved these muscles of articulation, the sensitivity and specificity of ECoG HGA were estimated relative to both ECS-induced impairments of naming and ECS disruption of mouth-related motor function. When these estimates were made separately for 12 electrode sites per patient (the average number with significant HGA), the specificity of ECoG HGA with respect to ECS was 78% for naming and 81% for mouth-related motor function, and equivalent sensitivities were 38% and 46%, respectively. When ECS maps of naming and mouth-related motor function were combined, the specificity and sensitivity of ECoG HGA with respect to ECS were 84% and 43%, respectively. This study indicates that event-related ECoG HGA during confrontation naming predicts ECS interference with naming and mouth-related motor function with good specificity but relatively low sensitivity. Its favourable specificity suggests that ECoG HGA can be used to construct a preliminary functional map that may help identify cortical sites of lower priority for ECS mapping. Passive recordings of ECoG gamma activity may be done simultaneously at all electrode sites without the risk of after-discharges associated with ECS mapping, which must be done sequentially at pairs of electrodes. We discuss the relative merits of these two functional mapping techniques.
The mechanism of essential tremor (ET) is unclear. Animal models of tremor and functional imaging studies in ET predict that the cerebellum and a cerebellar recipient thalamic nucleus (ventral intermediate, Vim) should exhibit oscillatory activity during rest and during tremor due to abnormal olivo-cerebellar activity. Physiologic responses of 152 single neurons were recorded during awake mapping of the ventral thalamus in seven patients with ET prior to thalamotomy. During postural tremor, spectral cross-correlation analysis demonstrated that 51% of the neurons studied exhibited a concentration of power at tremor frequency that was correlated with electromyography, i.e., tremor neurons. During rest, thalamic neurons did not exhibit tremor-frequency activity. Among the three thalamic nuclei surveyed, Vim had a significantly higher proportion of tremor neurons than did the principal somatic sensory nucleus (ventral caudal, Vc) or a pallidal recipient thalamic nucleus (ventral oral posterior, Vop). Neurons related to active movement (voluntary neurons) had significantly greater tremor-related activity than did nonvoluntary neurons. These findings are not consistent with a model of continuous olivo-cerebellar driving of the motor cortex through thalamic connections. Instead ET may be facilitated by motor circuits that enable tremor-related thalamic activity during voluntary movement. Additionally, a subgroup of tremor neurons with proprioceptive inputs were identified that may allow sensory feedback to access the central tremor network.
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The authors present the case of a 49-year-old woman with disabling bilateral upper-extremity cerebellar tremor that resolved unexpectedly after placement of an intrathecal baclofen pump for lower-extremity spasticity. The tremor amplitude decreased nearly linearly with increasing intrathecal baclofen dosage, and disappeared completely at a dose of 250 microg/day. In this report the authors demonstrate the role of the gamma-aminobutyric acidergic system in the pathogenesis of cerebellar tremor, and these findings may lead to a new treatment modality for patients disabled by this manifestation of their disease.
We review the techniques of physiological localization of the site for ventralis intermedius (Vim) thalamotomy or implantation of Vim-deep brain stimulation (DBS) for treatment of parkinsonian, essential, and intention tremor. Both microelectrode and semi-microelectrode techniques are reviewed. We believe the use of microelectrode and semi-microelectrode recordings in combination with Radiological landmarks provide the most accurate localization of the target. In addition to recording, microstimulation of subcortical structures such as Vim and thalamic nucleus ventralis caudal through the microelectrode may improve physiological identification by altering the tremor and evoking somatic sensations, respectively. Microelectrode recording provides the highest resolution picture of the target site at a cost of increased time to locate the target. We also review the relationship between thalamic neuronal firing and electromyographic activity during tremor. Implications of these results for the mechanisms for parkinsonian, essential, and intention tremors are discussed.
Many lines of evidence implicate the somatosensory areas near the lateral sulcus (Sylvian fissure) in the cortical representation of pain. Anatomical tracing studies in the monkey show nociceptive projection pathways to the vicinity of the secondary somatosensory cortex in the parietal operculum, and to anterior parts of insular cortex deep inside the Sylvian fissure. Clinical observations demonstrate alterations in pain sensation following lesions in these two areas in human parasylvian cortex. Imaging studies in humans reveal increased blood flow in parasylvian cortex, both contralaterally and ipsilaterally, in response to painful stimuli. Painful stimuli (such as laser radiant heat) evoke potentials with a scalp maximum at anterior temporal positions (T3 and T4). Several dipole source analyses as well as subdural recordings have confirmed that the earliest evoked potential following painful laser stimulation of the skin derives from sources in the parietal operculum. Thus, imaging and electrophysiological studies in humans suggest that parasylvian cortex is activated by painful stimuli, and is one of the first cortical relay stations in the central processing of these stimuli. There is mounting evidence for closely located but separate representations of pain (deep parietal operculum and anterior insula) and touch (secondary somatosensory cortex and posterior insula) in parasylvian cortex. This anatomical separation may be one of the reasons why single unit recordings of nociceptive neurons are scarce within regions comprising low-threshold mechanoreceptive neurons. The functional significance (sensory-discriminative, affective-motivational, cognitive-evaluative) of the closely spaced parasylvian cortical areas in acute and chronic pain is only poorly understood. It is likely that some of these areas are involved in sensory-limbic projection pathways that may subserve the recognition of potentially tissue damaging stimuli as well as pain memory.
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We have performed single unit analysis of the activity of cells located in the ventral nuclear group of thalamus in a patient with dysesthetic pain below the level of a clinically complete traumatic spinal cord transection at C5. Cells located in the parasagittal plane 14 mm lateral to the midline responded to tactile stimulation in small facial and intraoral receptive fields, which were characteristic of patients without somatosensory abnormality [30]. In this patient the 16 mm lateral parasagittal plane contained cells with receptive fields located on the occiput and neck instead of the upper extremity as would normally be expected. Cells with receptive fields on the neck and occiput had not previously been observed in recordings from single units (n = 531) responding to somatosensory stimulation [30]. Thus, on the basis of their location in a region of thalamus which normally represents parts of the body below the level of the spinal cord transection and their unusual receptive fields adjacent to these same parts of the body, we propose that the cells in the 16 mm lateral plane have lost their normal afferent input. Analysis of the autopower spectra of spike trains indicates that cells in the 16 mm lateral plane exhibited a higher mean firing rate and greater tendency to fire in bursts than cells in the 14 mm lateral plane (P less than 0.005). Finally, electrical stimulation at the recording sites in the 16 mm lateral plane evoked a burning sensation in the occiput, neck and upper extremity. These results suggest that regions of thalamus which have lost their normal somatosensory input contain neurons which exhibit abnormal spontaneous and evoked activity and that electrical stimulation of these regions can produce the sensation of burning dysesthesia.