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  • Magnetic Oculomotor Prosthetics for Acquired Nystagmus.

    15 February 2018

    PURPOSE: Acquired nystagmus, a highly symptomatic consequence of damage to the substrates of oculomotor control, often is resistant to pharmacotherapy. Although heterogeneous in its neural cause, its expression is unified at the effector-the eye muscles themselves-where physical damping of the oscillation offers an alternative approach. Because direct surgical fixation would immobilize the globe, action at a distance is required to damp the oscillation at the point of fixation, allowing unhindered gaze shifts at other times. Implementing this idea magnetically, herein we describe the successful implantation of a novel magnetic oculomotor prosthesis in a patient. DESIGN: Case report of a pilot, experimental intervention. PARTICIPANT: A 49-year-old man with longstanding, medication-resistant, upbeat nystagmus resulting from a paraneoplastic syndrome caused by stage 2A, grade I, nodular sclerosing Hodgkin's lymphoma. METHODS: We designed a 2-part, titanium-encased, rare-earth magnet oculomotor prosthesis, powered to damp nystagmus without interfering with the larger forces involved in saccades. Its damping effects were confirmed when applied externally. We proceeded to implant the device in the patient, comparing visual functions and high-resolution oculography before and after implantation and monitoring the patient for more than 4 years after surgery. MAIN OUTCOME MEASURES: We recorded Snellen visual acuity before and after intervention, as well as the amplitude, drift velocity, frequency, and intensity of the nystagmus in each eye. RESULTS: The patient reported a clinically significant improvement of 1 line of Snellen acuity (from 6/9 bilaterally to 6/6 on the left and 6/5-2 on the right), reflecting an objectively measured reduction in the amplitude, drift velocity, frequency, and intensity of the nystagmus. These improvements were maintained throughout a follow-up of 4 years and enabled him to return to paid employment. CONCLUSIONS: This work opens a new field of implantable therapeutic devices-oculomotor prosthetics-designed to modify eye movements dynamically by physical means in cases where a purely neural approach is ineffective. Applied to acquired nystagmus refractory to all other interventions, it is shown successfully to damp pathologic eye oscillations while allowing normal saccadic shifts of gaze.

  • Constitutive spectral EEG peaks in the gamma range: suppressed by sleep, reduced by mental activity and resistant to sensory stimulation.

    7 December 2017

    OBJECTIVE: In a systematic study of gamma activity in neuro-psychiatric disease, we unexpectedly observed distinctive, apparently persistent, electroencephalogram (EEG) spectral peaks in the gamma range (25-100 Hz). Our objective, therefore, was to examine the incidence, distribution and some of the characteristics of these peaks. METHODS: High sample-rate, 128-channel, EEG was recorded in 603 volunteers (510 with neuropsychiatric disorders, 93 controls), whilst performing cognitive tasks, and converted to power spectra. Peaks of spectral power, including in the gamma range, were determined algorithmically for all electrodes. To determine if peaks were stable, 24-h ambulatory recordings were obtained from 16 subjects with peaks. In 10 subjects, steady-state responses to stimuli at peak frequency were compared with off-peak-frequency stimulation to determine if peaks were a feature of underlying network resonances and peaks were evaluated with easy and hard versions of oddball tasks to determine if peaks might be influenced by mental effort. RESULTS: 57% of 603 subjects exhibited peaks >2 dB above trough power at or above 25 Hz. Larger peaks (>5 dB) were present in 13% of subjects. Peaks were distributed widely over the scalp, more frequent centrally. Peaks were present through the day and were suppressed by slow-wave-sleep. Steady-state responses were the same with on- or off-peak sensory stimulation. In contrast, mental effort resulted in reductions in power and frequency of gamma peaks, although the suppression did not correlate with level of effort. CONCLUSIONS: Gamma EEG can be expressed constitutively as concentrations of power in narrow or wide frequency bands that play an, as yet, unknown role in cognitive activity. SIGNIFICANCE: These findings expand the described range of rhythmic EEG phenomena. In particular, in addition to evoked, induced and sustained gamma band activity, gamma activity can be present constitutively in spectral peaks.

  • Visual Experiences during Paralysis.

    15 February 2018

    RATIONALE: Paralyzed human volunteers (n = 6) participated in several studies the primary one of which required full neuromuscular paralysis while awake. After the primary experiment, while still paralyzed and awake, subjects undertook studies of humor and of attempted eye-movement. The attempted eye-movements tested a central, intentional component to one's internal visual model and are the subject of this report. METHODS: Subjects reclined in a supportive chair and were ventilated after paralysis (cisatracurium, 20 mg intravenously). In illumination, subjects were requested to focus alternately on the faces of investigators standing on the left and the right within peripheral vision. In darkness, subjects were instructed to look away from a point source of light. Subjects were to report their experiences after reversal of paralysis. RESULTS: During attempted eye-movement in illumination, one subject had an illusion of environmental movement but four subjects perceived faces as clearly as if they were in central vision. In darkness, four subjects reported movement of the target light in the direction of attempted eye-movements and three could control the movement of the light at will. CONCLUSION: The hypothesis that internal visual models receive intended ocular-movement-information directly from oculomotor centers is strengthened by this evidence.

  • Electroencephalographic correlates of states of concentrative meditation.

    28 January 2018

    Meditative techniques aim for and meditators report states of mental alertness and focus, concurrent with physical and emotional calm. We aimed to determine the electroencephalographic (EEG) correlates of five states of Buddhist concentrative meditation, particularly addressing a correlation with meditative level. We studied 12 meditators and 12 pair-matched meditation-naïve participants using high-resolution scalp-recorded EEG. To maximise reduction of EMG, data were pre-processed using independent component analysis and surface Laplacian transformed data. Two non-meditative and five meditative states were used: resting baseline, mind-wandering, absorptions 1, 2, 3, 4 and 5 (corresponding to four levels of absorption and an absorption with a different object of focus, otherwise equivalent to level 4; these five meditative states produce repeatable, distinctly different experiences for experienced meditators). The experimental protocol required participants to experience the states in the order listed above, followed immediately by the reverse. We then calculated EEG power in standard frequency bands from 1 to 80Hz. We observed decreases of central scalp beta (13-25Hz), and central low gamma (25-48Hz) power in meditators during deeper absorptions. In contrast, we identified increases in frontal midline and temporo-parietal theta power in meditators, again, during deeper absorptions. Alpha activity was increased over all meditative states, not depth-related. This study demonstrates that the subjective experiences of deepening meditation partially correspond to measures of EEG. Our results are in accord with prior studies on non-graded meditative states. These results are also consistent with increased theta correlating with tightness of focus, and reduced beta/gamma with the desynchronization associated with enhanced alertness.

  • Mental tasks induce gamma EEG with reduced responsiveness in primary generalized epilepsies.

    7 December 2017

    PURPOSE: We previously revealed an interictal increase in intensity of EEG rhythms during quiescent mental activity in the 30- to 100-Hz frequency (gamma) range in primary generalized epilepsy (PGE). We have evidence that there is induction of gamma EEG in normal subjects in response to controlled mental activity. Here we test whether mental tasks further augment interictal gamma oscillations in people with PGE. METHODS: We recorded interictal EEG from patients with PGE and partial epilepsy and compared EEG power spectral responses (increases over resting) during mental tasks. RESULTS: In partial epilepsy, mental tasks (except for alternating checkerboard visual stimulation) induced 1.5- to 2.5-fold increases in power of gamma EEG. In generalized epilepsy, generalized increases of 1.5-fold in gamma EEG were induced by only two mental tasks (reading and subtraction), and enhancement of 1- to 1.5-fold in the remaining six (checkerboard, expectancy, music, learning, recalling, and a video). CONCLUSIONS: Gamma EEG is less responsive to mental activation in PGE than in partial epilepsy, confirming an abnormality in gamma mechanisms in PGE. Our findings also provide a possible mechanistic link between mental activity and seizures in reading- and arithmetic-induced seizures.

  • Cortical network dynamics during verbal working memory function.

    14 February 2018

    This study is an exploratory investigation of the regional timing of cortical activity associated with verbal working memory function. ERP activity was obtained from a single subject using a 124-channel sensor array during a task requiring the monitoring of imageable words for occasional targets. Distributed cortical activity was estimated every 2.5 ms with high spatial resolution using real head, boundary element modelling of non-target activity. High-resolution structural MRI was used for segmentation of tissue boundaries and co-registration to the scalp electrode array. The inverse solution was constrained to the cortical surface. Cortical activity was observed in regions commonly associated with verbal working memory function. This included: the occipital pole (early visual processing); the superior temporal and inferior parietal gyrus bilaterally and the left angular gyrus (visual and phonological word processing); the dorsal lateral occipital gyrus (spatial processing); and aspects of the bilateral superior parietal lobe (imagery and episodic verbal memory). Activity was also observed in lateral and superior prefrontal regions associated with working memory control of sensorimotor processes. The pattern of cortical activity was relatively stable over time, with variations in the extent and amplitude of contributing local source activations. By contrast, the pattern of concomitant scalp topography varied considerably over time, reflecting the linear summation effects of volume conduction that often confound dipolar source modelling.

  • Surface Laplacian of scalp electrical signals and independent component analysis resolve EMG contamination of electroencephalogram.

    7 December 2017

    The serious impact of electromyogram (EMG) contamination of electroencephalogram (EEG) is well recognised. The objective of this research is to demonstrate that combining independent component analysis with the surface Laplacian can eliminate EMG contamination of the EEG, and to validate that this processing does not degrade expected neurogenic signals. The method involves sequential application of ICA, using a manual procedure to identify and discard EMG components, followed by the surface Laplacian. The extent of decontamination is quantified by comparing processed EEG with EMG-free data that was recorded during pharmacologically induced neuromuscular paralysis. The combination of the ICA procedure and the surface Laplacian, with a flexible spherical spline, results in a strong suppression of EMG contamination at all scalp sites and frequencies. Furthermore, the ICA and surface Laplacian procedure does not impair the detection of well-known, cerebral responses; alpha activity with eyes-closed; ERP components (N1, P2) in response to an auditory oddball task; and steady state responses to photic and auditory stimulation. Finally, more flexible spherical splines increase the suppression of EMG by the surface Laplacian. We postulate this is due to ICA enabling the removal of local muscle sources of EMG contamination and the Laplacian transform being insensitive to distant (postural) muscle EMG contamination.

  • Scalp electrical recording during paralysis: quantitative evidence that EEG frequencies above 20 Hz are contaminated by EMG.

    19 February 2018

    OBJECTIVE: To identify the possible contribution of electromyogram (EMG) to scalp electroencephalogram (EEG) rhythms at rest and induced or evoked by cognitive tasks. METHODS: Scalp EEG recordings were made on two subjects in presence and absence of complete neuromuscular blockade, sparing the dominant arm. The subjects undertook cognitive tasks in both states to allow direct comparison of electrical recordings. RESULTS: EEG rhythms in the paralysed state differed significantly compared with the unparalysed state, with 10- to 200-fold differences in the power of frequencies above 20 Hz during paralysis. CONCLUSIONS: Most of the scalp EEG recording above 20 Hz is of EMG origin. Previous studies measuring gamma EEG need to be re-evaluated. SIGNIFICANCE: This has a significant impact on measurements of gamma rhythms from the scalp EEG in unparalysed humans. It is to be hoped that signal separation methods will be able to rectify this situation.