Search

A novel, spinal cord stimulation (SCS) system with a battery-free miniaturized implantable pulse generator (IPG) was used in this feasibility study. The system uses an external power source that communicates bidirectionally with the IPG ( 1.5 cmA prospective, multicenter, open-label clinical trial was initiated to evaluate the safety and performance of a novel miniaturized stimulator in the treatment of chronic, intractable leg and low-back pain. Eligible subjects were recruited for the study and gave consent. Subjects who passed the screening/trial phase (defined as ≥ 50% decrease in pain) continued to the long-term implant phase and were followed up at predefined time points after device activation. Interim clinical and usability outcomes were captured and reported at 90 days.Results of 22 subjects who chose a novel pulsed stimulation pattern therapy using the battery-free IPG ( 1.5 cmThese interim results from the ongoing study indicate the favorable efficacy and usability of a novel, externally powered, battery-free SCS IPG (1.5 cmThe Clinicaltrials.gov registration number for the study is ACTRN12618001862235.

Background Efficacy in deep brain stimulation (DBS) is dependent on precise positioning of electrodes within the brain. Intraoperative fluoroscopy, computed tomography (CT), or magnetic resonance imaging are used for stereotactic intraoperative localization (StIL), but the utility of biplanar X-ray has not been evaluated in detail. Objective To determine if analysis of orthogonal biplanar X-rays using graphical analysis (GA), ray tracing (RT), and/or perspective projection (PP) can be utilized for StIL. Methods A review of electrode tip positions comparing postoperative CT to X-ray methods was performed for DBS operations containing orthogonal biplanar X-ray with referential spheres and pins. Results Euclidean (Re) errors for final DBS electrode position on intraoperative X-rays vs postoperative CT using GA, RT, and PP methods averaged 1.58 mm (±0.75), 0.74 mm (±0.45), and 1.07 mm (±0.64), respectively (n = 56). GA was more accurate with a ventriculogram. RT and PP predicted positions that correlated with third ventricular structures on ventriculogram cases. RT was the most stable but required knowledge of the geometric setup. PP was more flexible than RT but required well-distributed reference points. A single case using the O-arm demonstrated Re errors of 0.43 mm and 0.28 mm for RT and PP, respectively. In addition, these techniques could also be used to calculate directional electrode rotation. Conclusion GA, RT, and PP can be employed for precise StIL during DBS using orthogonal biplanar X-ray. These methods may be generalized to other stereotactic procedures or instances of biplanar imaging such as angiograms, radiosurgery, or injection therapeutics.

The alpha rhythm is the longest-studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used microelectrodes and macroelectrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We first found that alpha in both visual and somatosensory cortex propagates from higher-order to lower-order areas. In posterior cortex, alpha propagates from higher-order anterosuperior areas toward the occipital pole, whereas alpha in somatosensory cortex propagates from associative regions toward primary cortex. Several analyses suggest that this cortical alpha leads pulvinar alpha, complicating prevailing theories of a thalamic pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortical layers. Together, these results suggest that the alpha rhythm likely reflects short-range supragranular feedback, which propagates from higher- to lower-order cortex and cortex to thalamus. These physiological insights suggest how alpha could mediate feedback throughout the thalamocortical system.

Facial pain is often debilitating and can be characterized by a sharp, stabbing, burning, aching, and dysesthetic sensation. Specifically, trigeminal neuropathic pain (TNP), anesthesia dolorosa, and persistent idiopathic facial pain (PIFP) are difficult diseases to treat, can be quite debilitating and an effective, enduring treatment remains elusive. We retrospectively reviewed our early experience with stimulation involving the trigeminal and sphenopalatine ganglion stimulation for TNP, anesthesia dolorosa, and PIFP between 2010–2014 to assess the feasibility of implanting at these ganglionic sites. Seven patients received either trigeminal and/or sphenopalatine ganglion stimulation with or without peripheral nerve stimulation, having failed multiple alternative modalities of treatment. The treatments were tailored on the physical location of pain to ensure regional coverage with the stimulation. Fluoroscopy or frameless stereotaxy was utilized to place the sphenopalatine and/or trigeminal ganglion stimulator. All patients were initially trialed before implantation. Trial leads implanted in the pterygopalatine fossa near the sphenopalatine ganglion were implanted via transpterygoid (lateral-medial, infrazygomatic) approach. Trial leads were implanted in the trigeminal ganglion via percutaneous Hartel approach, all of which resulted in masseter contraction. Patients who developed clinically significant pain improvement underwent implantation. The trigeminal ganglion stimulation permanent implants involved placing a grid electrode over Meckel’s cave via subtemporal craniotomy, which offered a greater ability to stimulate subdivisions of the trigeminal nerve, without muscular (V3) side effects. Two of the seven overall patients did not respond well to the trial and were not implanted. Five patients reported pain relief with up to 24-month follow-up. Several of the sphenopalatine ganglion stimulation patients had pain relief without any paresthesias. There were no electrode migrations or post-surgical complications. Refractory facial pain may respond positively to ganglionic forms of stimulation. It appears safe and durable to implant electrodes in the pterygopalatine fossa via a lateral transpterygoid approach. Also, implantation of an electrode grid overlying Meckel’s cave appears to be a feasible alternative to the Hartel approach. Further investigation is needed to evaluate the usefulness of these approaches for various facial pain conditions.

Summary Purpose: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. Methods: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation. Results: One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and “most severe” seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. Discussion: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.

It is widely accepted that patients with Parkinson's disease experience immediate but temporary improvement in motor signs after surgical implantation of subthalamic nucleus (STN) deep brain stimulating electrodes before the electrodes are activated, although this has never been formally studied. Based on anecdotal observations that limb mobility improved just after microelectrode recording (MER) during deep brain stimulation (DBS) procedures, we designed a prospective study to measure upper extremity bradykinesia using a quantitative measure of angular velocity. Measurements were made pre- and post-MER and during intraoperative DBS. Analysis of 98 STN DBS procedures performed on 61 patients showed that MER did not create adverse clinical symptoms despite concerns that MER increases morbidity. Quantitative upper extremity bradykinesia improved after MER alone, and further improvement was seen during intraoperative DBS. Electrophysiological data from each case were then compared to the improvement in bradykinesia post-MER alone and a significant correlation was found between the improvement in arm bradykinesia, the number of passes through the STN with somatosensory driving, and also with the number of arm cells with somatosensory driving in the STN, but not with total number of passes, total number of passes through the STN, or total number of cells with somatosensory driving in the STN. This study demonstrates that there is a significant improvement in upper extremity bradykinesia just after MER, before inserting or activating the DBS electrode in patients with Parkinson's disease who undergo STN DBS. © 2006 Movement Disorder Society

Postural control requires precise integration of sensory inputs and motor output, but clinical assessments of postural control do not differentiate between these. Previously, we found that this differentiation is important in Parkinson's disease (PD) as there was a dissociated effect of medication versus pallidotomy on sensory aspects of postural instability. In this study, we address several questions that emerged from that work in 28 different patients with PD off and on medication, before and after bilateral subthalamic nucleus deep brain stimulation (B-STN DBS): (1) In a different cohort is there still an unusually large percentage of patients with postural instability in sensory-deprived conditions? (2) Are more specific measures of motor aspects of postural control using dynamic posturography (postural movement velocity [MV] and reaction time [RT]) abnormal in PD as seen clinically using the Postural Instability and Gait Disorder score of the Unified Parkinson's Disease Rating Scale? (3) What is the effect of B-STN DBS versus medication on sensory versus motor aspects of postural instability in PD? The results included (1) substantially more patients (39%) versus controls (5%) exhibited postural instability in conditions of limited sensory feedback; (2) postural MV and postural RT were abnormal off medication preoperatively (N(subset) = 23; P < 0.001 for both); (3) B-STN DBS improved abnormal sensory aspects of postural instability (P < 0.05) and postural MV (P = 0.005), whereas medication did not. Neither B-STN DBS nor medication improved postural RT. For the group as a whole, STN DBS plus medication was better therapy than medication preoperatively for sensory aspects of postural control (P = 0.003).

Power spectra from local field potentials (LFPs) recorded post-operatively from the deep brain stimulation (DBS) macroelectrode show prominence of the beta rhythm (11-30 Hz) in untreated Parkinson's disease (PD). Dopaminergic medication and movement attenuate this beta band in PD. In this pilot study of six sides in four patients, we recorded LFPs from the DBS electrode in untreated PD patients in the operating room. In all cases, there was a peak in the time-frequency spectrogram in the beta frequency range when the patients were at rest, which was associated with attenuation in the same range with movement. The actual frequency range and the strength of the beta peak varied among cases. In two patients, intra-operative constraints permitted recording of LFPs at rest, before and immediately after subthalamic nucleus (STN) DBS. In both patients we documented that STN DBS caused a significant attenuation in power in the beta band at rest that persisted for 15-25 s after DBS had been turned off (P < 0.01). From one case, our data suggest that the beta rhythm attenuation was most prominent within the STN itself. This study shows for the first time that STN DBS attenuates the power in the prominent beta band recorded in the STN of patients with PD. These pilot findings raise the interesting possibility of using this biomarker for closed loop DBS or neuromodulation.

Object. The goal of this study was to determine the effect of hydrocephalus on cerebrospinal fluid (CSF) production rates in patients with acute and chronic hydrocephalus. Methods. The authors studied CSF production both in patients presenting with acute and chronic hydrocephalus, and patients with Parkinson disease (PD) of a similar mean age, whose CSF production was known to be normal. A modification of the Masserman method was used to measure CSF production through a ventricular catheter. The CSF production rates (means ± standard deviations) in the three groups were then compared. The patients with PD had a mean CSF production rate of 0.42 ± 0.13 ml/minute; this value lies within the normal range measured using this technique. Patients with acute hydrocephalus had a similar CSF production rate of 0.4 ± 0.13 ml/minute, whereas patients with chronic hydrocephalus had a significantly decreased mean CSF production rate of 0.25 ± 0.08 ml/minute. Conclusions. The authors postulate that chronic increased intracranial pressure causes downregulation of CSF production.

Purpose To investigate the peak temperature and thermal dose (T43) as tissue damage indicators for thermal therapy. Materials and Methods The proton resonant frequency (PRF) shift thermal coefficient was calibrated on six in vivo rabbit brains during interstitial laser ablation. The peak temperature and T43 were correlated with the lesion boundary observed on T2-weighted spin-echo (SE) MRI at 4 hours post-heating in seven thermal lesions using direct MR measurement and analysis based on a binary discriminate model. Results The peak temperature and T43 were 48.3 ± 1.7°C and 191 ± 219 minutes, respectively, from the direct MR measurement. The values derived by the binary discriminate analysis were 47.8 ± 2.2°C and 28 ± 41 minutes, respectively. Conclusion Our results suggest that tissue damage in rabbit brain 4 hours after thermal ablation can be predicted reliably from a threshold temperature of approximately 48°C. J. Magn. Reson. Imaging 2002;16:147–152. © 2002 Wiley-Liss, Inc.

Objective: To evaluate the production rate of CSF in patients with differing disease states. Methods: The authors measured the production rate of CSF in three groups of patients: five patients with PD below age 60 (aged 51 ± 4 years, mean ± SD), nine with PD over age 60 (aged 69 ± 6 years, mean ± SD), and seven with dementia of the Alzheimer’s type (AD) (aged 72 ± 9 years, mean ± SD). This method, based on the Masserman technique, employs ventricular rather than a lumbar access to the CSF space. Furthermore, the volume of CSF removed during the procedure is only 3 mL rather than 10 mL. Results: These measurements indicate that the mean rate of CSF production in patients with PD under age 60 was 0.47 ± 0.13 mL/minute, in patients with PD aged 60 or older the mean rate was 0.40 ± 0.12 mL/minute, and in patients with AD the mean rate was 0.20 ± 0.06 mL/minute. Conclusion: These results indicate that the rate of CSF production in patients with PD is normal, and that the rate of CSF production in patients with AD is markedly reduced.

Deep brain stimulation is a rapidly expanding therapy initially designed for the treatment of movement disorders and pain syndromes. The therapy includes implantation of electrodes in specific targets of the brain, delivering programmable small and safe electric impulses, like a pacemaker, that modulates both local and broad neurologic networks. The effects are thought to primarily involve a focus in the brain, probably inhibitory, which then restores a network of neural circuitry. Psychiatric diseases can be refractory and severe, leading to high medical costs, significant morbidity, and even death. Whereas surgery for psychiatric disease used to include destructive procedures, deep brain stimulation allows safe, reversible, and adjustable treatment that can be tailored for each patient. Deep brain stimulation offers new hope for these unfortunate patients, and the preliminary results are promising.

Patients with Parkinson’s disease (PD) become dependent upon caregivers because motor and cognitive disabilities interfere with their ability to carry out activities of daily living (ADLs). However, PD patients display diverse motor and cognitive symptoms, and it is not yet known which are most responsible for ADL dysfunction. The purpose of this study was to identify the contributions that specific cognitive and motor functions make to ADLs. Executive functioning, in particular sequencing, was a significant independent predictor of instrumental ADLs whereas simple motor functioning was not. By contrast, simple motor functioning, but not executive functioning, was a significant independent predictor of physical ADLs. Dementia severity, as measured by the Dementia Rating Scale, was significantly correlated with instrumental but not physical ADLs. The identification of selective relationships between motor and cognitive functioning and ADLs may ultimately provide a model for evaluating the benefits and limitations of different treatments for PD.

We report a technique based on patient-controlled stimulation to restore analgesia after development of tolerance to deep brain stimulation (DBS). A 45-year-old female with neurogenic pain after cerebellar stroke underwent DBS implantation in the right ventralis caudalis (VC) thalamus with excellent stimulus-controlled analgesia for 29 months, followed by development of tolerance and loss of analgesia. Analgesia was restored when a stimulation module that allowed patient-controlled stimulation was implanted.

Event-related potentials were recorded from 1221 sites in the medial, lateral and posterior aspects of the temporal lobe in 39 patients. Depth electrodes were implanted for about 4 days in order to localize seizure origin prior to surgical treatment. Subjects received an auditory discrimination task with target and non-target rare stimuli. In some cases, the target, distracting and frequent tones were completely balanced across blocks for pitch and volume. Some subjects also received an analogous visual discrimination task, or auditory tasks in which the rare target event was the omission of a tone, or the repetition of a tone within a series of alternating tones. In some subjects, the same auditory stimuli were delivered but the patient ignored them while reading. A complex field was recorded, indicating multiple components with overlapping time-courses, task correlates and generators. Two general patterns could be distinguished on the basis of their waveforms, latencies and task correlates. In the temporal pole and some middle temporal, posterior parahippocampal and fusiform gyrus sites, a sharp triphasic negative-positive-negative waveform with peaks at about 220-320-420 msec was usually observed. This wave was of relatively small amplitude and diffuse, and seldom inverted in polarity. It was multimodal but most prominent to auditory stimuli, appeared to remain when the stimuli were ignored, and was not apparent to repeated words and faces. A second broad, often monophasic, waveform peaking at about 380 msec was generated in the hippocampus, a limited region of the superior temporal sulcus, and (by inference) in the anterobasal temporal lobe (possible rhinal cortex). This waveform was of large amplitude, often highly focal, and could invert over short distances. It was equal to visual and auditory stimuli, was greatly diminished when the stimuli were ignored, and was also evoked by repeating words and faces. Preceding this waveform was a non-modality-specific negativity, possibly generated in rhinal cortex, and a visual-specific negativity in inferotemporal cortex. The early triphasic pattern may embody a diffuse non-specific orienting response that is also reflected in the scalp P3a. The late monophasic pattern may embody the cognitive closure that is also reflected in the scalp P3b or late positive component.

A 17-year-old woman with intractable seizures since infancy underwent resection of an epileptic focus in the left frontal cortex. The cytoplasm of many cortical astrocytes contained amorphous eosinophilic inclusions, which ultrastructurally were non-membrane bound and consisted of densely packed osmiophilic material. Similar inclusions have previously been observed, at autopsy, in patients with unspecified mental retardation and various brain malformations. The present report is unique in that the inclusions were detected in the resected specimen of an epileptic focus. The patient is neurologically intact except for the seizures that presently are totally controlled by the surgery. The pathogenesis of these inclusions is unclear. The fact they occurred in an epileptic focus raises the possibility that prolonged seizures or its underlying precipitating factors may cause conglutination of an indeterminate element of the protoplasmic astrocytes resulting in inclusion formation.

Evoked potentials (EPs) were used to help identify the timing, location, and intensity of the information-processing stages applied to faces and words in humans. EP generators were localized using intracranial recordings in 33 patients with depth electrodes implanted in order to direct surgical treatment of drug-resistant epilepsy. While awaiting spontaneous seizure onset, the patients gave their fully informed consent to perform cognitive tasks. Depth recordings were obtained from 1198 sites in the occipital, temporal and parietal cortices, and in the limbic system (amygdala, hippocampal formation and posterior cingulate gyrus). Twenty-three patients received a declarative memory recognition task in which faces of previously unfamiliar young adults without verbalizable distinguishing features were exposed for 300 ms every 3 s; 25 patients received an analogous task using words. For component identification, some patients also received simple auditory (21 patients) or visual (12 patients) discrimination tasks. Eight successive EP stages preceding the behavioral response (at about 600 ms) could be distinguished by latency, and each of 14 anatomical structures was found to participate in 2–8 of these stages. The earliest response, an N75-P105, focal in the most medial and posterior of the leads implanted in the occipital lobe (lingual g), was probably generated in visual cortical areas 17 and 18. These components were not visible in response to words, presumably because words were presented foveally. A focal evoked alpha rhythm to both words and faces was also noted in the lingual g. This was followed by an N130-P180-N240 focal and polarity-inverting in the basal occipitotemporal cortex (fusiform g, probably areas 19 and 37). In most cases, the P180 was evoked only by faces, and not by words, letters or symbols. Although largest in the fusiform g this sequence of potentials (especially the N240) was also observed in the supramarginal g, posterior superior and middle temporal g, posterior cingulate g, and posterior hippocampal formation. The N130, but not later components of this complex, was observed in the anterior hippocampus and amygdala. Faces only also evoked longer-latency potentials up to 600 ms in the right fusiform g. Words only evoked a series of potentials beginning at 190 ms and extending to 600 ms in the fusiform g and near the angular g (especially left). Both words and faces evoked a N150-P200-PN260 in the lingual g, and posterior inferior and middle temporal g. A N310-N430-P630 sequence to words and faces was largest and polarity-inverted in the hippocampal formation and amygdala, but was also probably locally-generated in many sites including the lingual g, lateral occipitotemporal cortex, middle and superior temporal g, temporal pole, supramarginal g, and posterior cingulate g. The P660 had the same distribution as has been noted for the P3b to rare target simple auditory and visual stimuli in ‘oddball’ tasks, with inversions in the hippocampus. In several sites, the N310 and N430 were smaller to repeated faces, and the P630 was larger. Putative information-processing functions were tentatively assigned to successive EP components based upon their cognitive correlates, as well as the functions and connections of their generating structures. For the N75-P105, this putative function is simple feature detection in primary visual cortex (V1 and V2). The N130-P180-N240 may embody structural face encoding in posterobasal inferotemporal cortex (homologous to V4?), with the results being spread widely to inferotemporal, multimodal and paralimbic cortices. For words, similar visual-form encoding (in fusiform g) or visual-phonemic encoding (in angular g) may occur between 150 and 280 ms. During the N310, faces and words may be multiply encoded for form and identity (inferotemporal), emotional (amygdala), recent declarative mnestic (hippocampal formation), and semantic (supramarginal and superior temporal sulcal supramodal cortices) characteristics. These multiple characteristics may be contextually integrated across inferotemporal, supramodal association, and limbic cortices during the N430, with cognitive closure following in the P630. In sum, visual information arrives at area 17 by about 75 ms, and is structurally-encoded in occipito-temporal cortex during the next 110 ms. By 150–200 ms after stimulus onset, activation has spread to parietal, lateral temporal, and limbic cortices, all of which continue to participate with the more posterior areas for the next 500 ms of event-encoding. Thus, face and word processing is serial in the sense that it can be divided into successive temporal stages, but highly parallel in that (after the initial stages where visual primitives are extracted) multiple anatomical areas with distinct perceptual, mnestic and emotional functions are engaged simultaneously. Consequently, declarative memory and emotional encoding can participate in early stages of perceptual, as well as later stages of cognitive integration. Conversely, occipitotemporal cortex is involved both early in processing (immediately after V1), as well as later, in the N430. That is, most stages of face and word processing appear to take advantage of the rich ‘upstream’ and ‘downstream’ anatomical connections in the ventral visual processing stream to link the more strictly perceptual networks with semantic, emotional, and mnestic networks.

Objective. Motor cortex stimulation (MCS) is increasingly being utilized for the treatment of intractable pain. While the risks of MCS are relatively low, focal or generalized seizures may be produced during programming of MCS systems. Occasionally, patients may experience seizures hours after programming. In order to understand this phenomenon better, we undertook a retrospective analysis of five patients in whom seizures limited the efficacy of MCS. Methods. A retrospective chart review was performed in five patients who underwent MCS between 2002 and 2006 and who had persistent seizures that limited programming. Results. The initial seizure during programming in these patients occurred at amplitudes of between 4.8 and 6.6 V. Four patients experienced generalized tonic-clonic seizures and one patient experienced focal seizures. Subsequent seizures occurred at amplitudes of between 4.4 and 5.5 V, with a tendency for seizure thresholds to progressively decrease. All five patients experienced at least one seizure occurring many minutes to hours after programming, with no side-effects initially observed once the final settings had been programmed. Four out of five patients were programmed with frequencies documented at between 70 and 90 Hz; documentation on frequency was unavailable for the remaining patient. One patient never achieved adequate pain relief and had the MCS system explanted. Conclusions. Despite the overall safety of MCS for the treatment of chronic pain, seizures during and after programming are a serious risk that should be anticipated. In this group of patients, seizures were associated only with stimulus rates between 70 and 90 Hz. No patient developed chronic epilepsy from the stimulation.

Background: Pain and pain-related diseases pose a major treatment challenge. Current medical treatments frequently provide inadequate pain control to patients, or cause dependence and other unwanted side-effects. Despite initial failures of open-label trials to show efficacy in the use of deep brain stimulation (DBS) for pain, several groups have reported utility of this modality on carefully selected patients. There are several characterized pain pathways in operation in the human brain. A common theme to the pathways thus far identified is their dependence on the neurotransmitter serotonin for modulation of pain. Deep brain stimulation for pain may well activate one of the serotonin-dependent pathways to stimulate relief. Greater experience, and improvements in both technology and patient selection, has paved the way for the potential use of electrical stimulation of subcortical structures to manage intractable and nociceptive pain syndromes and also for the mechanistic study of the pathways involved in the symptomatic relief of pain caused by stimulation.

Human medial temporal lobe neuronal activity and event-related potentials were recorded during the following behaviours: contextual recognition of words and faces, semantic discrimination of nonwords from words, and discrimination of stimulus classes based on perceptual attributes. Three distinct classes of behavioural correlates of unit activity were demonstrated by visual inspection of peristimulus histograms and by nonparametric statistics: (1) neuronal excitation during a keypress related to the subject's choice; (2) specific and nonspecific excitation to words; (3) excitation or inhibition to rare stimuli in a sensory discrimination task. Responses specifically to familiar (as opposed to unfamiliar) words or faces, or to tasks requiring recent memory per se were never seen. Keypress excitation was relatively common (32/76 units) and occurred regardless of whether the keypress target was a repeated or nonrepeated word, or the task required recent or remote semantic memory. In a more complex recognition task utilizing two responses and an imperative cue for the patient's response, units with prior keypress excitation failed to generate the response. This suggests that keypress excitation is not strictly tied either to response choice or to generation. The onset latencies and temporal relationship to event-related potentials of the nonspecific and specific excitation to words and the excitation to rare stimuli suggest that they represent contextual encoding of stimuli. Similar evidence suggests that the inhibition to rare stimuli represents inhibitory processes terminating contextual encoding. Thus human medial temporal lobe neurons seem to contribute information during successive stages of a cognitive stimulus-response task: contextual encoding, closure and response-selection.

The Unified Parkinson's Disease Rating Scale (UPDRS) is the primary outcome measure in most clinical trials of Parkinson's disease (PD) therapeutics. Each subscore of the motor section (UPDRS III) compresses a wide range of motor performance into a coarse-grained scale from 0 to 4; the assessment of performance can also be subjective. Quantitative digitography (QDG) is an objective, quantitative assessment of digital motor control using a computer-interfaced musical keyboard. In this study, we show that the kinematics of a repetitive alternating finger-tapping (RAFT) task using QDG correlate with the UPDRS motor score, particularly with the bradykinesia subscore, in 33 patients with PD. We show that dopaminergic medication and an average of 9.5 months of bilateral subthalamic nucleus deep brain stimulation (B-STN DBS) significantly improve UPDRS and QDG scores but may have different effects on certain kinematic parameters. This study substantiates the use of QDG to measure motor outcome in trials of PD therapeutics and shows that medication and B-STN DBS both improve fine motor control. © 2005 Movement Disorder Society

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is viewed by many as the ultimate therapy targeting severe advanced stages of Parkinson’s disease (PD). A fundamental constituent of the mechanisms underlying the therapeutic effects of DBS is clearly the functional organization of the STN; however, there is limited understanding of the organization of this structure in humans. Data from primates suggest that different domains can be identified in the STN, including a sensorimotor area with a segregated body map, as well as nonmotor areas. Recent clinical studies have used microelectrode recording to investigate the presence of a body map in the sensorimotor STN of PD patients. This paper will review and compare experimental and clinical data regarding the functional organization of the STN and discuss the clinical implications for PD patients undergoing STN DBS.

Growing experimental and clinical evidence supports the notion that the cortico-basal ganglia-thalamo-cortical loops proceed along parallel circuits linking cortical and subcortical regions subserving the processing of sensorimotor, associative and affective tasks. In particular, there is evidence that a strict topographic segregation is maintained during the processing of sensorimotor information flowing from cortical motor areas to the sensorimotor areas of the basal ganglia. The output from the basal ganglia to the motor thalamus, which projects back to neocortical motor areas, is also organized into topographically segregated channels. This high degree of topographic segregation is demonstrated by the presence of a well-defined somatotopic organization in the sensorimotor areas of the basal ganglia. The presence of body maps in the basal ganglia has become clinically relevant with the increasing use of surgical procedures, such as lesioning or deep brain stimulation, which are selectively aimed at restricted subcortical targets in the sensorimotor loop such as the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi). The ability to ameliorate the motor control dysfunction without producing side effects related to interference with non-motor circuits subserving associative or affective processing requires the ability to target subcortical areas particularly involved in sensorimotor processing (currently achieved only by careful intraoperative microelectrode mapping). The goal of this article is to review current knowledge about the somatotopic segregation of basal ganglia sensorimotor areas and outline in detail what is known about their body maps.

Multicontact microelectrodes were chronically implanted in epilepsy patients undergoing subdural grid implantation for seizure localization. Current source density and multiple unit activity of interictal spikes (IISs) were sampled every approximately 150 microm in a line traversing all layers of a cortical column. Our data suggest that interictal epileptiform events in humans are initiated by large postsynaptic depolarizations, consistent with the hypothesis that human IISs correspond to animal paroxysmal depolarization shifts. Furthermore, the cortical layer where the initial depolarization occurs may differ according to whether the IIS is locally generated or propagated from a distant location, and among the propagated IISs, whether the IIS is in the direct path of propagation or on the periphery of that path.

Object. The subthalamic nucleus (STN) is a key structure for motor control through the basal ganglia. The aim of this study was to show that the STN in patients with Parkinson disease (PD) has a somatotopic organization similar to that in nonhuman primates. Methods. A functional map of the STN was obtained using electrophysiological microrecording during placement of deep brain stimulation (DBS) electrodes in patients with PD. Magnetic resonance imaging was combined with ventriculography and intraoperative x-ray film to assess the position of the electrodes and the STN units, which were activated by limb movements to map the sensorimotor region of the STN. Each activated cell was located relative to the anterior commissure—posterior commissure line. Three-dimensional coordinates of the cells were analyzed statistically to determine whether those cells activated by movements of the arm and leg were segregated spatially. Three hundred seventy-nine microelectrode tracks were created during placement of 71 DBS electrodes in 44 consecutive patients. Somatosensory driving was found in 288 tracks. The authors identified and localized 1213 movement-related cells and recorded responses from 29 orofacial cells, 480 arm-related cells, 558 leg-related cells, and 146 cells responsive to both arm and leg movements. Leg-related cells were localized in medial (p < 0.0001) and ventral (p < 0.0004) positions and tended to be situated anteriorly (p = 0.063) relative to arm-related cells. Conclusions. Evidence of somatotopic organization in the STN in patients with PD supports the current theory of highly segregated loops integrating cortex—basal ganglia connections. These loops are preserved in chronic degenerative diseases such as PD, but may subserve a distorted body map. This finding also supports the relevance of microelectrode mapping in the optimal placement of DBS electrodes along the subthalamic homunculus.

Background: We present preliminary results using Cyberknife radiosurgery as a noninvasive treatment for trigeminal neuralgia (TN). Methods: Ten patients with medically refractory TN who were deemed unsuitable for conventional surgery underwent Cyberknife radiosurgery using CT cisternography for localization. Results: Pain relief was achieved in 7 patients, in 5 of them within 24–72 h after irradiation. Conclusion: Cyberknife radiosurgery can achieve early-onset pain relief in a subset of TN patients. Improvements using this technique include the absence of a stereotactic ring, potentially improved targeting accuracy produced by CT cisternography and improved dose homogeneity.

Radiosurgery is a non-invasive alternative to treat medically refractory trigeminal neuralgia (TN) in selected patients. Several reports have described outcomes after gamma knife radiosurgery (GKR)

The use of a new hybrid imaging system for guidance of a brain biopsy is described. The system combines the strengths of MRI (soft-tissue contrast, arbitrary plane selection) with those of x-ray fluoroscopy (high-resolution real-time projection images, clear portrayal of bony structures) and allows switching between the imaging modalities without moving the patient. The biopsy was carried out using x-ray guidance for direction of the needle through the foramen ovale and MR guidance to target the soft-tissue lesion. Appropriate samples were acquired. The system could be particularly effective for guidance of those cases where motion, swelling, resection and other intra-operative anatomical changes cannot be accounted for using traditional stereotactic-based imaging approaches.

✓ Holmes tremor is characterized by resting, postural, and intention tremor. Deep brain stimulation (DBS) of both the nucleus ventralis intermedius (Vim) and the subthalamic nucleus (STN) may be required to control these three tremor components. A 79-year-old man presented with a long-standing combination of resting, postural, and intention tremor, which was associated with severe disability and was resistant to medical treatment. Neuroimaging studies failed to reveal areas of discrete brain damage. A DBS device was placed in the Vim and produced an improvement in both the intention and postural tremor, but there was residual resting tremor, as demonstrated by clinical observation and quantitative tremor analysis. Placement of an additional DBS device in the STN resolved the resting tremor. Stimulation of the Vim or STN alone failed to produce global resolution of mixed tremor, whereas combined Vim—STN stimulation produced global relief without creating noticeable side effects. Combined Vim—STN stimulation can thus be a safe and effective treatment for Holmes tremor.

A laminar probe was chronically implanted in human putative MT+. The area was specifically responsive to globally coherent visual motion, a crucial aspect of the perception of movement through space. The probe contained 23 microcontacts spaced every 175μ in a linear array roughly perpendicular to the cortical surface. Current-source density (CSD) and multiunit activity (MUA) were recorded while viewing initially stationary random dot patterns that either moved incoherently or dilated from the central fixation. Onset of visual motion evoked large MUA/CSD activity, with coherent motion evoking earlier and faster-rising MUA/CSD activity than incoherent, in both superficial and deep pyramidal layers. The selective response, peaking at ≈115 ms, was especially large in deep pyramids, providing evidence that information necessary for visual flow calculations is projected from MT+ at an early latency to distant structures. The early onset of differential MUA/CSD implies that the selectivity of this area does not depend on recurrent inhibition or other intrinsic circuitry to detect coherent motion. The initially greater increase of MUA to coherent stimuli was followed by a greater decrease beginning at ≈133 ms, apparently because of recurrent inhibition. This resulted in the total MUA being greater to incoherent than coherent stimuli, whereas total rectified CSD was overall greater to coherent than to incoherent stimuli. However, MUA distinguished stationary from moving stimuli more strongly than did CSD. Thus, while estimates of total cell firing (MUA), and of total synaptic activity (CSD) generally correspond to previously reported BOLD results, they may differ in important details. Hum. Brain Mapping 13:226–238, 2001. © 2001 Wiley-Liss, Inc.

The human brain is dominated by the neocortex, a large folded surface, whose cellular and synaptic elements are arranged in layers. Since cortical structure is relatively constant across its surface, local information processing can be inferred from multiple laminar recordings of its electrical activity along a line perpendicular to its surface. Such recordings need to be spaced at least as close together as the cortical layers, and need to be wideband in order to sample both low frequency synaptic currents as well as high-frequency action potentials. Finally, any device used in the human brain must comply with strict safety standards. The current paper presents details of a system meeting these criteria, together with sample results obtained from epileptic subjects undergoing acute or chronic intracranial monitoring for definition of the epileptogenic region.

We present a method to reduce the geometric distortion in fast spin echo (FSE) images to levels appropriate for guiding stereotactic pallidotomy. We quantify the accuracy of FSE- guided target localization before and after correction using a cadaver head model. These results strongly suggest that stereotactic pallidotomy can be performed using MR and stimulation responses alone, thus avoiding the morbidity associated with pallidotomy and the costs of x-ray apparatus and personnel during surgery. This method, however, must be tested further and validated clinically before it can be applied.

Evoked potentials (EPs) were recorded from 991 frontal and peri-rolandic sites (106 electrodes) in 36 patients during an auditory discrimination task with target and non-target (distractor) rare stimuli. Variants of this task explored the effects of attention, dishabituation and stimulus characteristics (including modality). Rare stimuli evoked a widespread triphasic waveform with negative, positive and negative peaks at about 210, 280 and 390 msec, respectively. This waveform was identified with the scalp EP complex termed the N2a/P3a/slow wave and associated with orienting. It was evoked by rare target and distractor auditory and visual stimuli, as well as by rare stimulus repetitions or omissions. Across most frontal trajectories, N2a/P3a/SW amplitudes changed only slowly with distance. However, large (120 μV) P3as with steep voltage gradients were observed laterally, especially near the inferior frontal sulcus, and clear inversions of the P3a were noted in the orbito-frontal and the anterior cingulate cortices. The frontal P3a was earlier to distractor than to target stimuli, but only in some sites and with a latency difference much smaller than that observed at the scalp. Frontal P3a latencies were significantly shorter than those recorded simultaneously at the scalp and often were also shorter than P3a latency in the parietal or temporal lobes. In summary, this study demonstrates an early P3a-like activity that polarity inverts over short distances in the medial frontal lobe, and that it has a significantly shorter latency than similar potentials recorded in the temporal and parietal cortices.

Event-related potentials were recorded from 537 sites in the superior temporal plane and parietal lobe of 41 patients. Depth electrodes were implanted to localize seizure origin prior to surgical treatment. Subjects received an auditory discrimination task with target and non-target rare stimuli (“standard oddball paradigm”). In some cases, the target, distracting and frequent tones were completely balanced across blocks for pitch and volume. Variants included an analogous visual discrimination task, or auditory tasks where the rare target event was the omission of a tone, or the repetition of a tone within a series of alternating tones. In some subjects, the same auditory stimuli were delivered but the patient ignored them while reading. Three general response patterns could be distinguished on the basis of their wave forms, latencies and task correlates. First, potentials apparently related to rarity per se, as opposed to differences in sensory characteristics, or in habituation, were observed in the posterior superior temporal plane, beginning with a large positivity superimposed on early components. This positivity peaked at 150 msec after stimulus onset and inverted in sites superior to the Sylvian fissure. Subsequent components could be large, focal and/or inverting in polarity, and usually included a positivity at 230 msec and a negativity at 330 msec. All components in this area were specific to the auditory modality. Second, in the posterior cingulate and supramarginal gyri, a sharp triphasic negative-positive-negative wave form with peaks at about 210-300-400 msec was observed. This wave form was of relatively small amplitude and diffuse, and seldom inverted in polarity. It was multimodal but most prominent to auditory stimuli, appeared to remain when the stimuli were ignored, and was not apparent to repeated words and faces. Third, a broad, often monophasic, wave form peaking at about 380 msec was observed in the superior parietal lobe, similar to that which has been recorded in the hippocampus. This wave form could be of large amplitude, often highly focal, and could invert over short distances. It was equal to visual and auditory stimuli and was also evoked by repeating words and faces. The early endogenous activity in auditory cortex may embody activity that is antecedent to the other patterns in multimodal association cortex. The “triphasic” pattern may embody a diffuse non-specific orienting response that is also reflected in the scalp P3a. The later broad pattern may embody the cognitive closure that is also reflected in the scalp P3b or late positive component.

Evoked potentials (EPs) were recorded directly from 650 frontal and peri-Rolandic sites in 26 subjects during face and/or word recognition, as well as during control tasks (simple auditory and visual discrimination). Electrodes were implanted in order to localize epileptogenic foci resistant to medication, and thus direct their surgical removal. While awaiting spontaneous seizure onset, the patients gave informed consent to perform cognitive tasks during intracerebral EEG recording. The earliest potentials appeared to be related to sensory stimulation, were prominent in lateral prefrontal cortex, and occurred at peak latencies of about 150 and 190 ms. A small triphasic complex beginning slightly later (peak latencies about 200-285-350 ms) appeared to correspond to the scalp N2-P3a-slow wave, associated with non-specific orienting. Multiple components peaking from 280 to 900 ms, and apparently specific to words were occasionally recorded in the left inferior frontal g, pars triangularis (Broca's area). Components peaking at about 430 and 600 ms were recorded in all parts of the prefrontal cortex, but were largest (up to 180 microV) and frequently polarity-inverted in the ventro-lateral prefrontal cortex. These components appeared to represent the N4-P3b, which have been associated with contextual integration and cognitive closure. Finally, a late negativity (650-900 ms) was recorded in precentral and premotor cortices, probably corresponding to a peri-movement readiness potential. In summary, EP components related to early sensory processing were most prominent in lateral prefrontal, to orienting in medial limbic, to word-specific processing in Broca's area, to cognitive integration in ventro-lateral prefrontal, and to response organization in premotor cortices.(ABSTRACT TRUNCATED AT 250 WORDS)