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Biomedical subjects

R P Lesser

Publications and source records attributed to R P Lesser.

At least 19 recordsLinked to original sources

Electrocorticographic gamma activity during word production in spoken and sign language.

OBJECTIVE: To investigate the functional-neuroanatomic substrates of word production using signed versus spoken language. METHODS: The authors studied single-word processing with varying input and output modalities in a 38-year-old woman with normal hearing and speech who had become proficient in sign language 8 years before developing intractable epilepsy. Subdural electrocorticography (ECoG) was performed during picture naming and word reading (visual inputs) and word repetition (auditory inputs); these tasks were repeated with speech and with sign language responses. Cortical activation was indexed by event-related power augmentation in the 80- to 100-Hz gamma band, and was compared with general principles of functional anatomy and with subject-specific maps of the same or similar tasks using electrical cortical stimulation (ECS). RESULTS: Speech outputs activated tongue regions of the sensorimotor cortex, and sign outputs activated hand regions. In addition, signed word production activated parietal regions that were not activated by spoken word production. Posterior superior temporal gyrus was activated earliest and to the greatest extent during auditory word repetition, and the basal temporal-occipital cortex was activated similarly during naming and reading, reflecting the different modalities of input processing. With few exceptions, topographic patterns of ECoG gamma were consistent with ECS maps of the same or similar language tasks. CONCLUSIONS: Spoken and signed word production activated many of the same cortical regions, particularly those processing auditory and visual inputs; however, they activated different regions of sensorimotor cortex, and signing activated parietal cortex more than did speech. This study illustrates the utility of electrocorticographic gamma for studying the neuroanatomy and processing dynamics of human language.

Brain Mapping↗

Anterior spinal cord injury with preserved neurogenic 'motor' evoked potentials.

OBJECTIVE: To describe two cases in which intraoperative monitoring of neurogenic 'motor' evoked potentials (NMEPs) did not identify a spinal cord injury that resulted in paraplegia. METHODS: Bilateral tibial nerve somatosensory evoked potential (SEP) and NMEP testing was performed in two patients during spinal deformity corrective surgery using standard stimulation and recording parameters. These potentials were obtained repetitively throughout the primary procedures and were performed again during a subsequent procedure that took place after the discovery of paraplegia. RESULTS: SEP and NMEP signals were preserved in both patients and no adverse events were identified during the initial procedures. Postoperatively, paraplegia was identified immediately upon recovery from anesthesia and preserved posterior column function was apparent on clinical exam. In the procedures following the discovery of paraplegia, SEP and NMEP signals remained comparable with signals elicited in the initial surgeries. CONCLUSIONS: Based on these cases and previously published experimental evidence, we conclude that while 'NMEPs' remain a useful second test of spinal cord function, they are not reliable indicators of motor tract function. An alternate term, such as 'spinally-elicited peripheral nerve responses' should be used.

Adult↗

Brief bursts of pulse stimulation terminate afterdischarges caused by cortical stimulation.

OBJECTIVE: To determine whether cortical electrical stimulation can terminate bursts of epileptiform activity in humans, we used afterdischarges (ADs) as a model of epileptiform activity. METHODS: Cortical stimulation was performed for clinical localization purposes using subdural electrodes implanted in patients undergoing preresection evaluations for treatment of medically intractable seizures. We used 0.3-millisecond pulses of alternating polarity, repeated at 50 pulses/second. When stimulation produced AD, we often applied short additional brief bursts of pulse stimulation (BPS). We examined the effectiveness of BPS in aborting ADs in 17 patients using survival analysis. RESULTS: With BPS, ADs stopped within 2 seconds in 115 cases, 2 to 5 seconds in 22 cases, and in more than 5 seconds in 89 cases. Without BPS, ADs stopped within 2 seconds in 21 cases, 2 to 5 seconds in 114 cases, and in more than 5 seconds in 340 cases. BPS was an effective method to abort ADs (Cox proportional hazards model: p<0.0001). At any time during the course of ADs, the instantaneous rate of stopping ADs within 2 seconds after BPS was applied was 4.6 times greater than when BPS was not applied (95% CI = 3.7, 5.7). In eight cases, ADs progressed to the occurrence of clinical seizures, always when BPS was not applied. CONCLUSIONS: Afterdischarges significantly decreased in duration after we applied brief bursts of pulse stimulation. Although afterdischarges are not identical to spontaneous epileptiform activity, these results support the idea that electrical stimulation, applied in an appropriate manner at seizure onset, could abort seizures in humans.

Adolescent↗

Temporal dynamics of verbal object comprehension.

Knowledge of the stage composition and the temporal dynamics of human cognitive operations is critical for building theories of higher mental activity. This information has been difficult to acquire, even with different combinations of techniques such as refined behavioral testing, electrical recording/interference, and metabolic imaging studies. Verbal object comprehension was studied herein in a single individual, by using three tasks (object naming, auditory word comprehension, and visual word comprehension), two languages (English and Farsi), and four techniques (stimulus manipulation, direct cortical electrical interference, electrocorticography, and a variation of the technique of direct cortical electrical interference to produce time-delimited effects, called timeslicing), in a subject in whom indwelling subdural electrode arrays had been placed for clinical purposes. Electrical interference at a pair of electrodes on the left lateral occipitotemporal gyrus interfered with naming in both languages and with comprehension in the language tested (English). The naming and comprehension deficit resulted from interference with processing of verbal object meaning. Electrocorticography indices of cortical activation at this site during naming started 250-300 msec after visual stimulus presentation. By using the timeslicing technique, which varies the onset of electrical interference relative to the behavioral task, we found that completion of processing for verbal object meaning varied from 450 to 750 msec after current onset. This variability was found to be a function of the subject's familiarity with the objects.

Adult↗

Enhancing the detection of seizures with a clustering algorithm.

Automated detection algorithms of EEG seizures or similar clinical events typically analyze a finite epoch a given channel at a time, producing a probability or a weight estimating how likely it is for the event to resemble a clinical pattern. Epochs are normally shorter than the duration of a seizure, which may spread to more than one electrode. This may result in a weak correspondence between the seizure pattern in the record and its calculated detector event counterpart. As a result, such algorithms suffer from a high rate of false detections. We show that the weights/probabilities of a generic detector can be described as a weight function embedded in a directed graph (digraph). Extended objects such as seizures therefore correspond to the connected components of the digraph. We introduce a clustering algorithm that accounts for the shortcomings of a generic detector of the type described above. By correlating detector results with respect to both time and channel, we effectively extend the detection to an unlimited number of electrodes over an indefinite time. The algorithm is fast (linear - O(m)) and may be implemented in real time. We argue that the algorithm enhances the detection of seizure onset and lowers the rate of false detections. Preliminary results demonstrate a strong correlation between the seizure and the cluster's boundaries and over 50% reduction of false detection rate.

Algorithms↗

Functional mapping of human sensorimotor cortex with electrocorticographic spectral analysis. I. Alpha and beta event-related desynchronization.

Human scalp EEG studies have shown that event-related desynchronization (ERD) in the alpha (8-13 Hz) and beta (15-25 Hz) bands may be used to detect functional activation of sensorimotor cortex. However, in most previous studies somatotopy has not been examined in detail and brief, self-paced movements, focusing on the planning of motor output, have been used. We recorded electrocorticographic (ECoG) signals in five clinical subjects during a visual-motor decision task that was designed to activate the representations of different body parts in sensorimotor cortex. To focus more on execution of motor output than on its planning, subjects were instructed to make sustained isometric muscle contractions in different body parts (tongue protrusion, fist-clenching or foot dorsiflexion) in response to randomized visual stimuli depicting each action. ECoG spectral analysis utilized a mixed-effects analysis of variance model in which within-trial temporal dependencies were taken into account, and the magnitude and statistical significance of alpha and beta ERDs were mapped onto a surface rendering of each subject's brain MRI. Cortical electrical stimulation was performed in all subjects for clinical purposes, and the resulting maps of sensorimotor function were compared with those generated by ECoG spectral analysis. During the early phases of the motor responses, alpha ERD commonly occurred in a diffuse spatial pattern that was not somatotopically specific. During the late phases, the spatial pattern of alpha ERD usually became more focused and somatotopically specific. Maps of alpha ERD were closer to cortical stimulation maps when alpha ERD was sustained throughout the late phases of the motor responses. Thus, the topography of alpha ERD more resembled traditional somatotopy when its temporal profile approximated that of the motor response. The topography of beta ERD was often more discrete and somatotopically specific than that of alpha ERD, but beta ERD was often transient and sometimes absent. Sometimes, unilateral limb movement produced sustained alpha and beta ERD over bilateral sensorimotor cortices, with overlapping patterns for different body parts. The topographical spread of alpha ERD beyond expected functional-anatomical boundaries during early (and sometimes late) phases of motor responses invites a re-examination of traditional assumptions about sensorimotor functional neuroanatomy, as well as the role of alpha ERD as an index of cortical activation. We agree with others that the somatotopic representations of different body parts overlap more than previously thought. Also, unilateral limb movements may be associated with both contralateral and ipsilateral activation of sensorimotor cortex. We conjecture that alpha ERD may reflect activity within a broad synaptic network with distributed cortical representations.

Adult↗

Functional mapping of human sensorimotor cortex with electrocorticographic spectral analysis. II. Event-related synchronization in the gamma band.

It has been shown in animals that neuronal activity in the 'gamma band' (>30 Hz) is associated with cortical activation and may play a role in multi-regional and multi-modal integration of cortical processing. Studies of gamma activity in human scalp EEG have typically focused on event-related synchronization (ERS) in the 40 Hz band. To assess further the gamma band ERS further, as an index of cortical activation and as a tool for human functional brain mapping, we recorded subdural electrocorticographic (ECoG) signals in five clinical subjects while they performed visual-motor decision tasks designed to activate the representations of different body parts in sensorimotor cortex. ECoG spectral analysis utilized a mixed-effects analysis of variance model in which within-trial temporal dependencies were accounted for. Taking an exploratory approach, we studied gamma ERS in 10-Hz-wide bands (overlapping by 5 Hz) ranging from 30 to 100 Hz, and compared these findings with changes in the alpha (8-13 Hz) and beta (15-25 Hz) bands. Gamma ERS (observed in three out of subjects) occurred in two broad bands-'low gamma' included the 35-45 and 40-50 Hz bands, and 'high gamma' the 75-85, 80-90, 85-95 and 90-100 Hz bands. The temporal and spatial characteristics of low and high gamma ERS were distinct, suggesting relatively independent neurophysiological mechanisms. Low gamma ERS often began after onset of the motor response and was sustained through much of it, in parallel with event-related desynchronization (ERD) in the alpha band. High gamma ERS often began during, or slightly before, the motor response and was transient, ending well before completion of the motor response. These temporal differences in low and high gamma suggest different functional associations with motor performance. Compared with alpha and beta ERD, the topographical patterns of low and high gamma ERS were more discrete and somatotopically specific and only occurred over contralateral sensorimotor cortex during unilateral limb movements (alpha and beta ERD were also observed ipsilaterally). Maps of sensorimotor function inferred from gamma ERS were consistent with maps generated by cortical electrical stimulation for clinical purposes. In addition, different task conditions in one subject produced consistent differences in both motor response latencies and onset latency of gamma ERS, particularly high gamma ERS. Compared with alpha and beta ERD, the topography of gamma ERS is more consistent with traditional maps of sensorimotor functional anatomy. In addition, gamma ERS may provide complementary information about cortical neurophysiology that is useful for mapping brain function in humans.

Adult↗

An automated injection system (with patient selection) for SPECT imaging in seizure localization.

PURPOSE: Ictal single-photon-emission computed tomography (SPECT) provides lateralization but has technical limitations: (a) a "truly ictal" injection must be shortly after seizure onset; (b) therefore, a seizure of brief duration may be missed; (c) more than one patient may need testing at any given time; (d) a trained health professional must stay next to each patient to inject; and (e) because the radionuclide is placed in the syringe in advance of the injection, decay of the radioactive element could result in less than optimal uptake, if the same volume of material were to be used regardless of the time after ligand preparation. METHODS: We developed an automated method of ligand injection that shortens time and increases efficiency of ictal SPECT ligand injection. By using an experimental setup, we compared manual injection times with times using an automated injection system. We determined relative costs and efficiency in work hours for the manual and automated methods. RESULTS: Injection times were 8-14 s with automated versus 19-26 s with manual injection. Readjusting volume for "ligand" decay was simple and accurate with the automated system. Injection times for clinical SPECT studies in three patients were 13, 13, and 12 s, respectively. The price of one pump equals 120 work hours of a nurse or 24 ictal injection attempts. Much of the nurse's time is "wasted" because no seizure occurs. CONCLUSIONS: The method can be more efficient of staff, shorten injection time, and facilitate obtaining "truly ictal" injections. It allows more cost-effective use of personnel.

Algorithms↗

Motor and sensory mapping of the frontal and occipital lobes.

In patients with intractable epilepsy, surgical resections are performed with the primary goal of improving seizure control. The risk is that the resections may also remove tissues crucial for normal activities. The goal of surgical planning is therefore to determine as accurately as possible the regions of seizure onset and the regions controlling important functions, so that one can determine what to remove and what to leave in place. Clinical functional localization has been performed using cortical stimulation for over half a century, using both intraoperative and extraoperative methods. Signal averaging also has been widely used. More recently, techniques based on analysis of EEG in the frequency domain have shown promise. The methods appear to accurately indicate the function of the region assessed but do not necessarily predict functional consequences of resection. We review these methods, their indications, and the results obtained by their use.

Brain Mapping↗

Painful stimuli evoke potentials recorded over the human anterior cingulate gyrus.

Clinical studies of cingulotomy patients and imaging studies predict that the human cingulate gyrus might display pain-related activity. We now report potentials evoked by painful cutaneous stimulation with a CO2 laser (LEP) and recorded from subdural electrodes over the medial wall of the hemisphere. In response to facial laser stimulation on both sides, a negative (latency 211-242 ms) and then a positive wave (325-352 ms) were recorded from the cortex of right medial wall and from the falcine dura overlying the left medial wall. Medial wall LEPs were similar to scalp LEPs and were largest over the anterior cingulate and superior frontal gyri just anterior to motor cortex contralateral to the side of stimulation. These results demonstrate that there is significant direct nociceptive input to the human anterior cingulate gyrus (Brodmann's area 24).

Adult↗

Painful stimuli evoke potentials recorded from the parasylvian cortex in humans.

Cutaneous stimulation of the face and hand with a CO2 laser in three awake patients evoked potentials (LEPs) recorded from the dominant left parasylvian cortex. These were recorded by means of a subdural grid of electrodes implanted for evaluation of epilepsy. Stimulation of the contralateral face resulted in waveforms consisting of a negative potential (N2, 162 +/- 5 ms; mean +/- SE) followed by a positive potential (P2, 340 +/- 18 ms). Both waves occurred at longer latency after hand than after facial stimulation. N2 and P2 potentials recorded from the grid correspond well in morphology to those recorded from the scalp in four additional patients tested with the same stimulation paradigm. The N2 waves recorded from the subdural grid occurred at significantly shorter latencies than did those recorded from the scalp (184 +/- 6 ms), but the P2 waves at the grid occurred at significantly longer latencies than did those recorded at the scalp (281 +/- 13 ms). The amplitudes of the potentials recorded from the grid were maximal over the parietal operculum both for contralateral stimulation of the face or hand and for ipsilateral stimulation of the face. Potentials also were recorded in this area after stimulation of the ipsilateral hand. The cortical distributions of these potentials suggest that their generators are located in the parietal operculum or in the insula, or in both, consistent with previous PET, magnetoencephalographic, and scalp LEP source analyses. These previous analyses provide indirect evidence of nociceptive input to parasylvian cortex because the interpretation of each analysis incorporates multiple assumptions. The present results are the first direct evidence of nociceptive input to the human parasylvian cortex.

Adult↗

Right hemisphere speech perception revealed by amobarbital injection and electrical interference.

OBJECTIVE: To investigate the right hemispheric speech perception capabilities of an adult right-handed patient with seizures. METHODS: Consecutive, unilateral, intracarotid sodium amobarbital injections and left hemispheric electrical interference mapping were used to determine lateralization and localization of speech perception, measured as syllable discrimination. RESULTS: Syllable discrimination remained intact after left and right intracarotid sodium amobarbital injections. Language otherwise strongly lateralized to the left hemisphere. Despite evidence of bilateral speech perception capabilities, electrical interference testing in the left posterior temporal lobe impaired syllable discrimination. CONCLUSIONS: The results suggest a functionally symmetric, parallel system in the adult brain with preferential use of left hemispheric pathways for speech perception.

Adult↗