Perceived timing of cutaneous vibration and intracortical microstimulation of human somatosensory cortex.

BACKGROUND: Intracortical microstimulation (ICMS) of somatosensory cortex can partially restore the sense of touch. Though ICMS bypasses much of the neuraxis, prior studies have found that conscious detection of touch elicited by ICMS lags behind the detection of cutaneous vibration. These findings may have been influenced by mismatched stimulus intensities, which can impact temporal perception. OBJECTIVE: Evaluate the relative latency at which intensity-matched vibration and ICMS are perceived by a human participant. METHODS: One person implanted with microelectrode arrays in somatosensory cortex performed reaction time and temporal order judgment (TOJ) tasks. To measure reaction time, the participant reported when he perceived vibration or ICMS. In the TOJ task, vibration and ICMS were sequentially presented and the participant reported which stimulus occurred first. To verify that the participant could distinguish between stimuli, he also performed a modality discrimination task, in which he indicated if he felt vibration, ICMS, or both. RESULTS: When vibration was matched in perceived intensity to high-amplitude ICMS, vibration was perceived, on average, 48 ms faster than ICMS. However, in the TOJ task, both sensations arose at comparable latencies, with points of subjective simultaneity not significantly different from zero. The participant could discriminate between tactile modalities above chance level but was more inclined to report feeling vibration than ICMS. CONCLUSIONS: The latencies of ICMS-evoked percepts are slower than their mechanical counterparts. However, differences in latencies are small, particularly when stimuli are matched for intensity, implying that ICMS-based somatosensory feedback is rapid enough to be effective in neuroprosthetic applications.

Spatially distributed computation in cortical circuits.

The traditional view of neural computation in the cerebral cortex holds that sensory neurons are specialized, i.e., selective for certain dimensions of sensory stimuli. This view was challenged by evidence of contextual interactions between stimulus dimensions in which a neuron's response to one dimension strongly depends on other dimensions. Here, we use methods of mathematical modeling, psychophysics, and electrophysiology to address shortcomings of the traditional view. Using a model of a generic cortical circuit, we begin with the simple demonstration that cortical responses are always distributed among neurons, forming characteristic waveforms, which we call neural waves. When stimulated by patterned stimuli, circuit responses arise by interference of neural waves. Results of this process depend on interaction between stimulus dimensions. Comparison of modeled responses with responses of biological vision makes it clear that the framework of neural wave interference provides a useful alternative to the standard concept of neural computation.

Intracortical microstimulation of somatosensory cortex enables object identification through perceived sensations.

Advances in brain-machine interfaces have helped restore function and independence for individuals with sensorimotor deficits; however, providing efficient and effective sensory feedback remains challenging. Intracortical microstimulation (ICMS) of sensorimotor brain regions is a promising technique for providing bioinspired sensory feedback. In a human participant with chronically-implanted microelectrode arrays, we provided ICMS to the primary somatosensory cortex to generate tactile percepts in his hand. In a 3-choice object identification task, the participant identified virtual objects using tactile sensory feedback and no visual information. We evaluated three different stimulation paradigms, each with a different weighting of the grip force and its derivative, to explore the potential benefits of a more bioinspired stimulation strategy. In all paradigms, the participant's ability to identify the objects was above-chance, with object identification accuracy reaching 80% correct when using only sustained grip force feedback and 76.7% when using equal weighting of both sustained grip force and its derivative. These results demonstrate that bioinspired ICMS can provide sensory feedback that is functionally beneficial in sensorimotor tasks. Designing more efficient stimulation paradigms is important because it will allow us to 1) provide safer stimulation delivery methods that reduce overall injected charge without sacrificing function and 2) more effectively transmit sensory information to promote intuitive integration and usage by the human body.

Mechanisms of Spatiotemporal Selectivity in Cortical Area MT.

Cortical sensory neurons are characterized by selectivity to stimulation. This selectivity was originally viewed as a part of the fundamental "receptive field" characteristic of neurons. This view was later challenged by evidence that receptive fields are modulated by stimuli outside of the classical receptive field. Here, we show that even this modified view of selectivity needs revision. We measured spatial frequency selectivity of neurons in cortical area MT of alert monkeys and found that their selectivity strongly depends on luminance contrast, shifting to higher spatial frequencies as contrast increases. The changes of preferred spatial frequency are large at low temporal frequency, and they decrease monotonically as temporal frequency increases. That is, even interactions among basic stimulus dimensions of luminance contrast, spatial frequency, and temporal frequency strongly influence neuronal selectivity. This dynamic nature of neuronal selectivity is inconsistent with the notion of stimulus preference as a stable characteristic of cortical neurons.

Recovery of rod photoresponses in ABCR-deficient mice.

PURPOSE: The ABCR protein of the rod outer segment is thought to facilitate movement of the all-trans retinal photoproduct of rhodopsin bleaching out of the disc lumen. This study was undertaken to investigate the extent to which ABCR deficiency affects the post-bleach recovery of the rod photoresponse in ABCR-deficient (abcr-/-) mice. METHODS: Electroretinographic (ERG) a-wave responses were recorded from abcr-/- mice and two control strains. A bright probe flash was used to examine the course of rod recovery after fractional rhodopsin bleaches of approximately 10(-6), approximately 3 x 10(-5), approximately 0.03, and approximately 0.30 to approximately 0.40. RESULTS: Dark-adapted abcr-/- mice and control animals exhibited similar normalized near-peak amplitudes of the paired-flash-ERG-derived, weak-flash response. Response recovery after approximately 10(-6) bleaching exhibited an average exponential time constant of 319, 171, and 213 ms, respectively, in the abcr-/- and the two control strains. Recovery time constants determined for approximately 3 x 10(-5) bleaching did not differ significantly among strains. However, those determined for the approximately 0.03 bleach indicated significantly faster recovery in abcr-/- mice (2.34 +/- 0.74 minutes) than in the controls (5.36 +/- 2.20 and 5.92 +/- 2.44 minutes). After approximately 0.30 to approximately 0.40 bleaching, the initial recovery in the abcr-/- mice was, on average, faster than in control mice. CONCLUSIONS: By comparison with control animals, abcr-/- mice exhibit faster rod recovery after a bleach of approximately 0.03. The data suggest that ABCR in normal rods may directly or indirectly prolong all-trans retinal clearance from the disc lumen over a significant bleaching range, and that the essential function of ABCR may be to promote the clearance of residual amounts of all-trans retinal that remain in the discs long after bleaching.

Survival and early differentiation of human neural stem cells transplanted in a nonhuman primate model of stroke.

OBJECT: Neural cell transplantation has been proposed as a treatment after stroke. The purpose of this study was to establish if human neural stem cells (HNSCs) could survive in the nonhuman primate brain after an ischemic event. METHODS: Three adult cynomolgus monkeys received a unilateral occlusion of the M, segment of the right middle cerebral artery (MCA). One week later each animal received five magnetic resonance (MR) image-guided stereotactic intracerebral injections of HNSC neurospheres labeled with bromodeoxyuridine (BrdU) in the areas surrounding the ischemic lesion as defined in T1- and T2-weighted images. On the day of transplantation and throughout the study the monkeys received oral cyclosporine (10 mg/kg twice a day), and plasma levels were monitored routinely. The animals were killed at 45, 75, or 105 days after transplantation. Magnetic resonance images revealed a cortical and subcortical infarction in the MCA distribution area. Postmortem morphological brain analyses confirmed the distribution of the infarcted area seen in the MR images, with loss of tissue and necrosis in the ischemic region. Cells that were positive for BrdU were present in the three experimental monkeys, mainly along injection tracks. Double-label immunofluorescence for BrdU and betaIII-tubulin (a marker of young neurons) revealed colocalization of few HNSCs, most of which were observed outside the immediate injection site. Colocalization with nestin was also observed, indicating an early neural/glial fate. CONCLUSIONS: In a model of stroke in nonhuman primates, HNSCs can survive up to 105 days when transplanted 1 week after an ischemic event and can partly undergo neuronal differentiation.