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Biomedical subjects

William D Hutchison

Publications and source records attributed to William D Hutchison.

At least 19 recordsLinked to original sources
PubMed2006

Saccade-related potentials recorded from human subthalamic nucleus.

OBJECTIVE: To investigate an ocular motor role for the STN in Parkinson's disease (PD) patients. METHODS: Potentials were recorded from deep brain stimulation (DBS) electrodes implanted in the vicinity of STN in five PD patients, while patients simultaneously performed visually cued saccades, self-paced saccades and in two patients self-paced wrist extensions. RESULTS: Premovement potentials related to visually cued saccades were found in 4/5 patients and 56% (5/9) of potentials showed phase reversal indicating a local generator. Onsets of these potentials began closer to saccade initiation from STN contacts (0.88+/-0.30s) than thalamic ones (1.39+/-0.28 s). Self-paced saccade-related potentials were found in 4/4 patients. Self-paced saccade potential onsets (1.82+/-0.88 s) were not different from self-paced wrist extension onsets (1.27+/-0.98 s), suggesting a non-specific mechanism could be responsible for both potentials. 50% (3/6) of potentials to self-paced saccades and 66% (2/3) of potentials to self-paced wrist extensions showed phase reversal. Potentials could be found either ipsilaterally or contralaterally with respect to saccade direction. CONCLUSIONS: These subcortical premovement potentials to saccades are similar to Bereitschaftspotentials and contingent negative variations to limb movements recorded in cortical and subcortical regions. SIGNIFICANCE: These studies further support a role of STN in ocular motor control and suggest a common mechanism of motor preparation for both eye and limb movements in the basal ganglia.

Adult↗
PubMed2006

Beta oscillatory activity in the subthalamic nucleus and its relation to dopaminergic response in Parkinson's disease.

Recent studies suggest that beta (15-30 Hz) oscillatory activity in the subthalamic nucleus (STN) is dramatically increased in Parkinson's disease (PD) and may interfere with movement execution. Dopaminergic medications decrease beta activity and deep brain stimulation (DBS) in the STN may alleviate PD symptoms by disrupting this oscillatory activity. Depth recordings from PD patients have demonstrated beta oscillatory neuronal and local field potential (LFP) activity in STN, although its prevalence and relationship to neuronal activity are unclear. In this study, we recorded both LFP and neuronal spike activity from the STN in 14 PD patients during functional neurosurgery. Of 200 single- and multiunit recordings 56 showed significant oscillatory activity at about 26 Hz and 89% of these were coherent with the simultaneously recorded LFP. The incidence of neuronal beta oscillatory activity was significantly higher in the dorsal STN (P = 0.01) and corresponds to the significantly increased LFP beta power recorded in the same region. Of particular interest was a significant positive correlation between the incidence of oscillatory neurons and the patient's benefit from dopaminergic medications, but not with baseline motor deficits off medication. These findings suggest that the degree of neuronal beta oscillatory activity is related to the magnitude of the response of the basal ganglia to dopaminergic agents rather than directly to the motor symptoms of PD. The study also suggests that LFP beta oscillatory activity is generated largely within the dorsal portion of the STN and can produce synchronous oscillatory activity of the local neuronal population.

Aged↗
PubMed2006

Toxicity of indoxacarb and spinosad to the multicolored Asian lady beetle, Harmonia axyridis (Coleoptera: Coccinellidae), via three routes of exposure.

The use of selective insecticides may improve conservation of natural enemies and therefore contribute to the success of integrated pest management (IPM) programs. In this study, the toxicity of two commonly used selective insecticides, indoxacarb and spinosad, to the multicolored Asian lady beetle, Harmonia axyridis (Pallas), was evaluated. Third instars and adults of H. axyridis were exposed to indoxacarb at 50 and 100% of the field rate (FR), to spinosad at 100% FR and to water (untreated check) under laboratory conditions via three routes of exposure. Treatments were applied directly on insects (i.e., topical application), on Petri dishes (i.e., residues), or on soybean aphids, Aphis glycines Matsumara (i.e., treated prey). Mortality of exposed individuals in each life stage was recorded 2 and 7 days after treatment. Logistic regression indicated that indoxacarb at 100% FR, followed by indoxacarb at 50% FR, was more insecticidal than spinosad to third instars. Mortality was higher when H. axyridis were exposed to both insecticides via residues followed by treated prey. Indoxacarb at 100 or 50% FR was insecticidal to adults. Adults were tolerant to spinosad via all routes of exposure. The present results suggest that indoxacarb may decrease H. axyridis field populations by causing mortality to larvae and adults via all routes of exposure. Implications of the toxicity of indoxacarb to H. axyridis within an IPM context and possible reasons for the differences in susceptibility of H. axyridis for each route of exposure are discussed.

Animals↗
PubMed2005

Human anterior cingulate cortex neurons encode cognitive and emotional demands.

The cortical mechanisms and substrates of cognitive and emotional demands are poorly understood. Lesion studies and functional imaging implicate the anterior cingulate cortex (ACC). The caudal ACC (cACC) has been implicated in cognitive processes such as attention, salience, interference, and response competition, mostly on the basis of neuroimaging results. To test the hypothesis that individual cACC neurons subserve these functions, we monitored neuronal activity from single cells in the cACC while subjects were engaged in a mental arithmetic task, the cognitively demanding counting Stroop task, and/or the emotional Stroop interference task. We now report the first direct measures of single neurons in humans identifying a population of cACC neurons that respond differentially or in a graded manner to cognitively demanding high- and low-conflict Stroop tasks, including those with emotional valence. These data indicate that cACC neurons may be acting as salience detectors when faced with conflict and difficult or emotional stimuli, consistent with neuroimaging results of cACC responses to abrupt sensory, novel, task-relevant, or painful stimuli.

Brain Mapping↗
PubMed2005

Firing rates of pallidal neurons are similar in Huntington's and Parkinson's disease patients.

According to the now classical basal ganglia-thalamocortical circuitry model, the chorea of Huntington's disease (HD) and the hypokinesia in Parkinson's disease (PD) are explained by a decrease in the inhibitory output (reduced firing rates) from the globus pallidus internus (GPi) in HD and increased output in PD. Differences between firing patterns might also be a factor contributing to the different symptoms, however. To test the predictions of the model we examined neuronal firing rates and patterns in two HD patients and 14 PD patients. Single-cell, microelectrode recordings were obtained from awake patients undergoing stereotactic surgery for implantation of deep brain stimulating (DBS) electrodes in the GPi. The mean neuronal firing rate in the GPi of HD patients was 81.8+/-4.3 Hz (mean+/-SEM), which was not significantly different from that in PD patients (89.9+/-3.0 Hz). Firing pattern analyses using measurements of burst index, coefficient of variation, and percentage participation of spikes in bursts revealed, however, that GPi neurons in HD patients fired in a more regular pattern (fewer "bursts") than in PD patients. These results suggest that the rate-based model does not adequately explain the motor abnormalities present in the two HD patients studied. Furthermore, the findings did reveal a difference between firing patterns in the HD and PD groups, thereby supporting the role of altered firing patterns in the pathophysiology of these diseases.

Action Potentials↗
PubMed2005

Pallidal deep brain stimulation influences both reflexive and voluntary saccades in Huntington's disease.

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is being evaluated as a potential new therapy for patients with Huntington's disease (HD). In addition to skeletal movement disorders, HD patients have difficulty initiating voluntary saccades and have difficulty in suppressing rapid saccades toward newly appearing stimuli. We measured several saccade parameters in an HD patient who had marked improvement of clinical symptoms with bilateral GPi DBS to determine whether oculomotor performance improved in parallel with clinical scores. Oculomotor performance was assessed using three testing paradigms: pro-saccades, anti-saccades, and memory-guided saccades. The data from the HD patient was also compared to that of two healthy controls. Pallidal DBS decreased pro-saccade latency, total movement time, and the number of correctly executed trials, as well as increasing saccade gain. Memory-saccade performance was negatively affected with stimulation: saccade gain decreased, latency increased, and the patient's ability to suppress unwanted saccades decreased with stimulation. Our data demonstrate a task-specific improvement of oculomotor deficits in this HD patient with pallidal DBS, supporting a role of GPi in oculomotor control.

Adult↗
PubMed2004

Eye movement-related responses of neurons in human subthalamic nucleus.

Intraoperative microelectrode single unit recordings are routinely made in the subthalamic nucleus (STN) of awake and alert Parkinson's disease (PD) patients during surgery for implantation of deep brain stimulation (DBS) electrodes. These recordings not only assist in determining the optimal target for electrode implantation, but also offer the unique opportunity to study movement-evoked responses from the basal ganglia. We report on the responses of human STN neurons to eye movements from eight PD patients (five men and three women). Twenty percent (18/89) of tested STN neurons showed responses to eye movements. Patients made pro-saccades, voluntary saccades or smooth pursuit eye movements in four directions: up, down, left, right. The majority of STN neurons (72% or 13/18), that responded to eye movements were found in the ventral half of the nucleus, while 58% (22/38) of STN neurons that had somatic responses were found in the dorsal half of the nucleus. The firing rate for STN oculomotor neurons was 33+/-15 Hz (n = 18), which was not different from that reported previously for STN neurons. Most neurons only responded to eye movements in a single direction, but 17% (3/18) showed responses to more than one direction. The majority of responses (17/18) to eye movements were increases in firing rate although one neuron did show a pause in firing with eye movement onset. The phasic changes in firing rate in response to eye movement usually occurred up to 250 ms following eye movement onset. Neurons were found that showed task-specific responses to cued versus self-paced saccades, responded to both passive limb movement and voluntary eye movement, and appeared to show either visual or attentional responses. These human physiological data, in conjunction with previous anatomical studies, suggest that the STN might have an oculomotor role. Although there is no evidence that STN is responsible for driving eye movements, it may have a role in either sensory feedback, corollary discharge, or in focusing the substantia nigra pars reticulata to allow a saccade to occur through disinhibition of the superior colliculus.

Action Potentials↗
PubMed2004

Very fast oscillations evoked by median nerve stimulation in the human thalamus and subthalamic nucleus.

Very fast oscillations (VFOs; 500-1,500 Hz) are associated with sensory-evoked potentials (SEPs), but their origin is unknown. To characterize the origins of VFOs, we studied 35 patients with deep brain stimulation (DBS) electrodes [15 with thalamic and 20 with the subthalamic nucleus (STN) electrodes]. We recorded median nerve stimulation-evoked SEPs from the thalamus and STN with microelectrodes during stereotactic surgery and from the contacts of the DBS electrodes postoperatively. We also examined the firing of individual neurons in thalamus in relation to the VFOs. In the thalamus, VFOs with frequencies around 1,000 Hz were superimposed on slow potentials. Both slow and fast SEP components showed phase reversals in the somatosensory thalamus [ventralis caudalis (Vc)]. Median nerve poststimulus time histograms showed that single thalamic neurons fired at preferred times at intervals between 0.8 to 1.2 ms that were synchronous with the VFOs, although the neurons fired only once or a few times per trial. In the STN, low-amplitude SEPs with VFOs were observed at a latency similar to the thalamic SEPs. The VFOs from STN probably represent volume conduction, possibly from the medial lemniscus. We conclude that the thalamic VFOs are generated within Vc and that they induce time-locked firing in a network of neurons.

Adult↗
PubMed2004

Stimulation-induced inhibition of neuronal firing in human subthalamic nucleus.

The subthalamic nucleus (STN) is an important component of the basal ganglia (BG) and plays a major role in the pathogenesis of Parkinson's disease (PD). Hyperactivity of STN as a consequence of the loss of dopaminergic inputs to the BG is believed to be a major factor in producing the motor symptoms of PD. High-frequency (HF) deep brain stimulation (DBS) of the STN has recently become an important treatment in PD patients where medications no longer provide satisfactory therapy. However, the mechanisms underlying DBS therapy are unknown, and there is seemingly conflicting data suggesting inhibition or excitation of STN neurons. This study directly examined the effects of stimulation in STN on the activity of STN neurons in PD patients during functional stereotactic mapping prior to insertion of DBS electrodes. Electrical stimulation in STN was investigated in twelve PD patients by recording the neural activity of a cell in STN with one electrode while applying current pulses through a second electrode located about 600 microm away. Stimulation at high frequencies (100-300 Hz) was found to produce inhibition following the stimulus train in 42% of the 60 cells tested. Inhibition during the train was seen in 13 of 15 neurons where it was possible to detect such activity. Furthermore, in 44% of the cases where HF stimulation produced inhibition there was an early inhibition followed by rebound excitation and a further inhibitory period, suggesting that the inhibitions observed are due to hyperpolarization. In eight of the 25 neurons inhibited by HF stimulation, the effects of single stimuli were determined and revealed that in seven of these there was an inhibitory period of 15-20 ms following each stimulus. Thus, the present findings suggest that local HF stimulation inhibits many STN neurons. However, these studies could not determine whether the stimulus also directly excited the cell and/or its axon, but other recent findings suggest that this is likely the case. Therefore, the overall effects of DBS stimulation in STN are likely to be inhibition of intrinsic and synaptically mediated activity, and its replacement by regular high-frequency firing.

Action Potentials↗
PubMed2004

Bilateral globus pallidus stimulation for Huntington's disease.

Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) was performed in a patient with Huntington's disease (HD) with severe chorea. Stimulation at 40 and 130 Hz improved chorea. Stimulation at 130 Hz slightly worsened bradykinesia overall, whereas 40 Hz had little effect. A [15O] H2O positron emission tomography showed increased regional cerebral blood flow in motor decision making and execution areas more evident at 40 Hz. Adjustment of stimulation parameters in GPi DBS may have the potential to optimize the motor response in HD, improving chorea without aggravating bradykinesia.

Adult↗
PubMed2004

Neuronal activity in the globus pallidus of multiple system atrophy patients.

The pathophysiological changes in neural activity that characterize multiple system atrophy (MSA) are largely unknown. We recorded the activity of pallidal neurons in 3 patients with clinical and radiological features of MSA who underwent unilateral microelectrode-guided pallidotomy for disabling parkinsonism. Findings in these patients were compared with 4 control patients with a clinical diagnosis of Parkinson's disease (PD). The position, firing rates, and firing patterns of single neurons in the pallidal complex were analyzed in both MSA and PD patients. The mean spontaneous firing rate of neurons in the internal segment of the globus pallidus internus (GPii) was significantly lower in MSA than in PD patients. There were no significant differences between MSA and PD patients, however, in firing rates of neurons in the external globus pallidus (GPe) or in the external segment of GPi (GPie). In addition, no significant differences in firing pattern were found between MSA and PD patients. In conclusion, this study has shown that firing rates of neurons in GPii but not in GPie and GPe are different in MSA patients compared with that in PD patients, a finding that may reflect the poor clinical results of pallidotomy reported in patients with MSA.

Adult↗
PubMed2004

Somatosensory evoked potentials (SEPs) recorded from deep brain stimulation (DBS) electrodes in the thalamus and subthalamic nucleus (STN).

OBJECTIVE: To examine the location of deep brain stimulation (DBS) electrode somatosensory evoked potentials (SEPs) and determine the generators of the median nerve SEPs recorded in thalamus and subthalamic nucleus (STN). METHODS: SEPs were recorded from contacts of DBS electrodes and microelectrodes in thalamus and STN to establish the latencies of N13, N18 and N20 in 24 patients (8 tremor, 4 chronic pain, 12 Parkinson disease) undergoing chronic DBS. RESULTS: A large SEP with a mean latency of 17.9+/-1.7 ms was recorded from thalamic contacts. Phase reversal occurred at the horizontal level of the anterior commissure-posterior commissure line. Smaller potentials with similar latency but no reversal could be recorded from STN electrodes. CONCLUSIONS: We propose that the thalamic SEP is generated by excitatory post-synaptic potentials in sensory relay neurons in nucleus ventrocaudalis. A small potential in STN at a similar latency, may be due to volume conduction from thalamus. Intraoperative and postoperative SEP recordings from DBS electrodes could be used to determine the optimal position of the contacts relative to the sensory pathways and the choice of contacts for chronic stimulation.

Adult↗
PubMed2004

Cingulotomy for psychiatric disease: microelectrode guidance, a callosal reference system for documenting lesion location, and clinical results.

OBJECTIVE: To evaluate magnetic resonance imaging (MRI)- and microelectrode recording-guided cingulotomy for patients with psychiatric disorders and to develop a new method of mapping lesion location in anterior cingulate cortex that takes into account the significant interindividual variability in callosal morphometry. METHODS: MRI and microelectrode recording were used to guide placement of radiofrequency lesions in patients with obsessive-compulsive disorder (n = 21) or affective disorders (n = 5). Postoperative improvement was evaluated with the Yale-Brown Obsessive-Compulsive Scale in 15 of the 21 obsessive-compulsive disorder patients studied. From the postoperative MRI scans, we developed a coordinate system for position in the anterior cingulate cortex. The callosal line passes from the most anterior point of the corpus callosum (c = 0) to the most posterior (c = 100). We reconstructed the lesions onto a sagittal map from the Talairach and Tournoux atlas using the distance along the callosal line and the distance above the upper surface of the corpus callosum. RESULTS: The location of neuronal activity distinguished gray and white matter and was useful in delineating the upper and lower cortical banks of the cingulate gyrus, the cingulate bundle, and the corpus callosum. This information was used to place the lesions. Lesions typically were 6 to 8 mm in diameter on T2-weighted MRI scans. The inferior margins were along the corpus callosum from c = 16 to c = 38. Four of 15 patients with obsessive-compulsive disorder had a documented decrease of more than 35% on the Yale-Brown Obsessive-Compulsive Scale, but only one patient had a sustained benefit for more than 1 year. CONCLUSION: Microelectrode recording is useful for lesion placement. Our system for reporting location in anterior cingulate cortex normalizes for differences in callosal morphometry. These techniques may aid future study.

Adult↗
PubMed2003

Pallidal neuronal activity: implications for models of dystonia.

Dystonia is a neurological syndrome involving sustained contractions of opposing muscles leading to abnormal movements and postures. Recent studies report abnormally low pallidal neuronal activity in patients with generalized dystonia, suggesting hyperkinetic disorders result from underactive basal ganglia output. We examined this hypothesis in 11 patients with segmental and generalized dystonia undergoing microelectrode exploration of the internal globus pallidus (GPi) before pallidotomy or deep brain stimulation (DBS) implantation. The mean firing rates and firing patterns were compared with those in six patients with Parkinson's disease (PD). In seven patients who underwent surgery under local anesthesia, the mean GPi firing rate was 77 Hz, similar to the 74 Hz observed in the PD patients. However, in three dystonic patients under propofol anesthesia, GPi mean firing rate was much reduced (31 Hz), and the firing pattern was distinguished by long pauses in activity, as reported by others. Low-dose propofol in one other dystonia patient also seemed to suppress GPi firing. These results indicate that an abnormally low basal ganglia output is not the sine qua non of dystonia. The widely accepted pathophysiological models of dystonia that propose global decreases in basal ganglia output need to be viewed with caution in light of these findings.

Adolescent↗
PubMed2002

Synchronized neuronal discharge in the basal ganglia of parkinsonian patients is limited to oscillatory activity.

It has been proposed that an increase in synchronization between neurons in the basal ganglia contributes to the clinical features of Parkinson's disease (PD). To examine this hypothesis, we looked for correlations in the discharge activity of pairs of neurons in the globus pallidus internus (GPi), globus pallidus externus (GPe), and the substantia nigra pars reticulata (SNr). Recordings were performed in PD patients undergoing functional stereotactic mapping for pallidotomy (eight patients) or subthalamic nucleus deep brain stimulation (four patients). A double-microelectrode setup was used to simultaneously record from neurons separated by distances as small as 250 microm. In the five pallidotomy patients without limb tremor during the procedure, none of the 73 GPi pairs and 15 GPe pairs displayed synchronous activity. In the three pallidotomy patients with limb tremor, 6 of 21 GPi pairs and 5 of 29 GPe pairs displayed oscillatory synchronization in the frequency range of the ongoing limb tremor (3-6 Hz) or at higher frequencies (15-30 Hz). Synchronized activity was not observed in the SNr (10 pairs). The findings indicate that oscillatory synchronization between pairs of GPi or GPe neurons is found in patients with limb tremor. These results also suggest that overt neuronal synchronization, which may be attributable to an increase in direct synaptic connections or common collateral afferent inputs, is not present in the basal ganglia of patients with PD.

Action Potentials↗
PubMed2002

Microelectrode recordings in the pallidum.

The internal segment of the globus pallidus (GPi) is being targeted in neurosurgical procedures to treat Parkinson's disease and dystonia. Precise targeting of the pallidal complex is important in determining the efficacy of the surgical intervention and for the avoidance of adverse effects. Intraoperative microelectrode recording can be used to characterize the patterns of activity and receptive field properties of single pallidal neurons and to identify important bordering structures, including the optic tract and internal capsule. Because the clinical features of movement disorders can be differentially affected as a function of location within the pallidal complex, further refinements in intraoperative targeting may become important.

Brain Mapping↗
PubMed2002

Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson's disease.

Local field potentials and pairs of neurones in the subthalamic nucleus (STN) of patients with Parkinson's disease show high-frequency oscillations (HFOs) at 15-30 Hz. This study explores how these HFOs are modulated by voluntary movements and by dopaminergic medication. We examined 15 patients undergoing implantation of bilateral deep brain stimulating electrodes using microelectrode recordings of pairs of STN neurones (eight patients) and macroelectrode recordings of local field potentials from the STN (14 patients). Synchronized HFOs between STN neurones were observed in 28 out of 37 pairs in five patients who had tremor in the operating room and none of 45 pairs in three patients who did not. In two of the three non-tremulous patients, HFOs in the frequency spectra of local field potentials were detected but were weaker than in those patients with tremor. Active movement suppressed synchronized HFOs in three out of five pairs of neurones, independent of changes in firing rate. HFOs observed in the local field potentials in nine out of 14 patients were reduced with voluntary movement in six of the eight patients tested. Dopaminergic medication decreased the incidence of synchronized HFOs in STN neurone pairs, reduced HFO synchrony in a pair of tremor cells concurrent with a reduction in firing rate and limb tremor, and decreased HFOs of local field potentials in the STN. These results demonstrate that HFO synchronization in the STN is reduced by voluntary movements and by exogenous dopaminergic medication. A mechanism for neuronal oscillatory synchronization in basal ganglia is proposed. It is suggested that the firing of STN neurones can be synchronized by 15-30 Hz cortical beta oscillatory activity, particularly when dopamine deficiency results in a higher background firing rate of STN neurones, and that this synchronization contributes to parkinsonian pathophysiology.

Action Potentials↗