Bis-cyclooctatetraenyl Thulium(II): Highly Reducing Lanthanide Sandwich Single Molecule Magnets.

Divalent lanthanide organometallics are well-known highly reducing compounds usually used for single electron transfer reactivity and small molecule activation. Thus, their very reactive nature prevented for many years the study of their physical properties, such as magnetic studies on a reliable basis. In this article, the access to rare organometallic sandwich compounds of TmII with the cyclooctatetraenyl (Cot) ligand impacts on the use of divalent organolanthanide compounds as an additional strategy for the design of performing Single Molecule Magnets (SMM). Herein, the first divalent thulium sandwich complex with f13 configuration behaving as a Single Molecule Magnet in absence of DC field is highlighted.

Neural subspaces of imagined movements in parietal cortex remain stable over several years in humans.

Objective.A crucial goal in brain-machine interfacing is the long-term stability of neural decoding performance, ideally without regular retraining. Long-term stability has only been previously demonstrated in non-human primate experiments and only in primary sensorimotor cortices. Here we extend previous methods to determine long-term stability in humans by identifying and aligning low-dimensional structures in neural data.Approach.Over a period of 1106 and 871 d respectively, two participants completed an imagined center-out reaching task. The longitudinal accuracy between all day pairs was assessed by latent subspace alignment using principal components analysis and canonical correlations analysis of multi-unit intracortical recordings in different brain regions (Brodmann Area 5, Anterior Intraparietal Area and the junction of the postcentral and intraparietal sulcus).Main results.We show the long-term stable representation of neural activity in subspaces of intracortical recordings from higher-order association areas in humans.Significance.These results can be practically applied to significantly expand the longevity and generalizability of brain-computer interfaces.Clinical TrialsNCT01849822, NCT01958086, NCT01964261.

Quantifying physical degradation alongside recording and stimulation performance of 980 intracortical microelectrodes chronically implanted in three humans for 956-2246 days.

Motivation: The clinical success of brain-machine interfaces depends on overcoming both biological and material challenges to ensure a long-term stable connection for neural recording and stimulation. Therefore, there is a need to quantify any damage that microelectrodes sustain when they are chronically implanted in the human cortex. Methods: Using scanning electron microscopy (SEM), we imaged 980 microelectrodes from Neuroport arrays chronically implanted in the cortex of three people with tetraplegia for 956-2246 days. We analyzed eleven multi-electrode arrays in total: eight arrays with platinum (Pt) electrode tips and three with sputtered iridium oxide tips (SIROF); one Pt array was left in sterile packaging, serving as a control. The arrays were implanted/explanted across three different clinical sites surgeries (Caltech/UCLA, Caltech/USC and APL/Johns Hopkins) in the anterior intraparietal area, Brodmann's area 5, motor cortex, and somatosensory cortex.Human experts rated the electron micrographs of electrodes with respect to five damage metrics: the loss of metal at the electrode tip, the amount of separation between the silicon shank and tip metal, tissue adherence or bio-material to the electrode, damage to the shank insulation and silicone shaft. These metrics were compared to functional outcomes (recording quality, noise, impedance and stimulation ability). Results: Despite higher levels of physical degradation, SIROF electrodes were twice as likely to record neural activity than Pt electrodes (measured by SNR), at the time of explant. Additionally, 1 kHz impedance (measured in vivo prior to explant) significantly correlated with all physical damage metrics, recording, and stimulation performance for SIROF electrodes (but not Pt), suggesting a reliable measurement of in vivo degradation.We observed a new degradation type, primarily occurring on stimulated electrodes ("pockmarked" vs "cracked") electrodes; however, tip metalization damage was not significantly higher due to stimulation or amount of charge. Physical damage was centralized to specific regions of an array often with differences between outer and inner electrodes. This is consistent with degradation due to contact with the biologic milieu, influenced by variations in initial manufactured state. From our data, we hypothesize that erosion of the silicon shank often precedes damage to the tip metal, accelerating damage to the electrode / tissue interface. Conclusions: These findings link quantitative measurements, such as impedance, to the physical condition of the microelectrodes and their capacity to record and stimulate. These data could lead to improved manufacturing or novel electrode designs to improve long-term performance of BMIs making them are vitally important as multi-year clinical trials of BMIs are becoming more common.

Neural subspaces of imagined movements in parietal cortex remain stable over several years in humans.

A crucial goal in brain-machine interfacing is long-term stability of neural decoding performance, ideally without regular retraining. Here we demonstrate stable neural decoding over several years in two human participants, achieved by latent subspace alignment of multi-unit intracortical recordings in posterior parietal cortex. These results can be practically applied to significantly expand the longevity and generalizability of future movement decoding devices.

A shared neural substrate for action verbs and observed actions in human posterior parietal cortex.

High-level sensory and motor cortical areas are activated when processing the meaning of language, but it is unknown whether, and how, words share a neural substrate with corresponding sensorimotor representations. We recorded from single neurons in human posterior parietal cortex (PPC) while participants viewed action verbs and corresponding action videos from multiple views. We find that PPC neurons exhibit a common neural substrate for action verbs and observed actions. Further, videos were encoded with mixtures of invariant and idiosyncratic responses across views. Action verbs elicited selective responses from a fraction of these invariant and idiosyncratic neurons, without preference, thus associating with a statistical sampling of the diverse sensory representations related to the corresponding action concept. Controls indicated that the results are not the product of visual imagery or arbitrary learned associations. Our results suggest that language may activate the consolidated visual experience of the reader.

Encoding of spatial location by posterior parietal neurons.

The cortex of the inferior parietal lobule in primates is important for spatial perception and spatially oriented behavior. Recordings of single neurons in this area in behaving monkeys showed that the visual sensitivity of the retinotopic receptive fields changes systematically with the angle of gaze. The activity of many of the neurons can be largely described by the product of a gain factor that is a function of the eye position and the response profile of the visual receptive field. This operation produces an eye position-dependent tuning for locations in head-centered coordinate space.

Reach plans in eye-centered coordinates.

The neural events associated with visually guided reaching begin with an image on the retina and end with impulses to the muscles. In between, a reaching plan is formed. This plan could be in the coordinates of the arm, specifying the direction and amplitude of the movement, or it could be in the coordinates of the eye because visual information is initially gathered in this reference frame. In a reach-planning area of the posterior parietal cortex, neural activity was found to be more consistent with an eye-centered than an arm-centered coding of reach targets. Coding of arm movements in an eye-centered reference frame is advantageous because obstacles that affect planning as well as errors in reaching are registered in this reference frame. Also, eye movements are planned in eye coordinates, and the use of similar coordinates for reaching may facilitate hand-eye coordination.

Mechanisms of heading perception in primate visual cortex.

When we move forward while walking or driving, what we see appears to expand. The center or focus of this expansion tells us our direction of self-motion, or heading, as long as our eyes are still. However, if our eyes move, as when tracking a nearby object on the ground, the retinal image is disrupted and the focus is shifted away from the heading. Neurons in primate dorso-medial superior temporal area responded selectively to an expansion focus in a certain part of the visual field, and this selective region shifted during tracking eye movements in a way that compensated for the retinal focus shift. Therefore, these neurons account for the effect of eye movements on what we see as we travel forward through the world.

Reaches to sounds encoded in an eye-centered reference frame.

A recent hypothesis suggests that neurons in the lateral intraparietal area (LIP) and the parietal reach region (PRR) encode movement plans in a common eye-centered reference frame. To test this hypothesis further, we examined how PRR neurons encode reach plans to auditory stimuli. We found that PRR activity was affected by eye and initial hand position. Population analyses, however, indicated that PRR neurons were affected more strongly by eye position than by initial hand position. These eye position effects were appropriate to maintain coding in eye coordinates. Indeed, a significant population of PRR neurons encoded reaches to auditory stimuli in an eye-centered reference frame. These results extend the hypothesis that, regardless of the modality of the sensory input or the eventual action, PRR and LIP neurons represent movement plans in a common, eye-centered representation.

Mechanism of gain modulation at single neuron and network levels.

Gain modulation, in which the sensitivity of a neural response to one input is modified by a second input, is studied at single-neuron and network levels. At the single neuron level, gain modulation can arise if the two inputs are subject to a direct multiplicative interaction. Alternatively, these inputs can be summed in a linear manner by the neuron and gain modulation can arise, instead, from a nonlinear input-output relationship. We derive a mathematical constraint that can distinguish these two mechanisms even though they can look very similar, provided sufficient data of the appropriate type are available. Previously, it has been shown in coordinate transformation studies that artificial neurons with sigmoid transfer functions can acquire a nonlinear additive form of gain modulation through learning-driven adjustment of synaptic weights. We use the constraint derived for single-neuron studies to compare responses in this network with those of another network model based on a biologically inspired transfer function that can support approximately multiplicative interactions.

Visual self-motion perception during head turns.

Extra-retinal information is critical in the interpretation of visual input during self-motion. Turning our eyes and head to track objects displaces the retinal image but does not affect our ability to navigate because we use extra-retinal information to compensate for these displacements. We showed observers animated displays depicting their forward motion through a scene. They perceived the simulated self-motion accurately while smoothly shifting the gaze by turning the head, but not when the same gaze shift was simulated in the display; this indicates that the visual system also uses extra-retinal information during head turns. Additional experiments compared self-motion judgments during active and passive head turns, passive rotations of the body and rotations of the body with head fixed in space. We found that accurate perception during active head turns is mediated by contributions from three extra-retinal cues: vestibular canal stimulation, neck proprioception and an efference copy of the motor command to turn the head.

Evidence for the lateral intraparietal area as the parietal eye field.

It has long been appreciated that the posterior parietal cortex plays a role in the processing of saccadic eye movements. Only recently has it been discovered that a small cortical area, the lateral intraparietal area, within this much larger area appears to be specialized for saccadic eye movements. Unlike other cortical areas in the posterior parietal cortex, the lateral intraparietal area has strong anatomical connections to other saccade centers, and its cells have saccade-related responses that begin before the saccades. The lateral intraparietal area appears to be neither a strictly visual nor strictly motor structure; rather it performs visuomotor integration functions including determining the spatial location of saccade targets and forming plans to make eye movements.

Coordinate transformations in the representation of spatial information.

Coordinate transformations are an essential aspect of behavior. They are required because sensory information is coded in the coordinates of the sensory epithelia (e.g. retina, skin) and must be transformed to the coordinates of muscles for movement. In this review we will concentrate on recent studies of visual-motor transformations. The studies show that representations of space are distributed, being specified in the activity of many cells rather than in the activity of individual cells. Furthermore, these distributed representations appear to be derived by a specific operation, which systematically combines visual signals with eye and head position signals.

Accumulation of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone in alkaloid genotypes of burley tobacco during postharvest processing: comparisons with N'-nitrosonornicotine and probable nitrosamine precursors.

Recent work showed that 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was present in some cured tobacco and was more carcinogenic than N'-nitrosonornicotine (NNN). In the present investigation, the concentration relationships of NNK, NNN, and their probable precursors, i.e., nitrite, nitrate, and alkaloids, were determined: (a) after the growth of Ky 14 burley tobacco under different shade conditions followed by air curing; and (b) during preparation of air-cured and homogenized-leaf-cured (HLC) burley tobaccos from conventionally grown tobaccos of different alkaloid genotypes. A capillary gas chromatography-nitrogen-phosphorus detector procedure was developed and utilized for quantitative determinations of NNK and NNN. NNK contents ranged from 0.2 to 0.5 micrograms/g in air-cured Ky 14 tobacco lamina from leaves grown under 0 to 65% shade (100, 65, and 35% of natural daylight). The highest NNK concentrations were from 45% shade-grown lamina from lower leaf positions on stalks. Concentrations of NNK did not correlate significantly with those of either nitrate or total alkaloids calculated over all shade treatments and stalk positions. During HLC tobacco processing, the following significant correlations of NNK with precursor content changes were found for each of four burley alkaloid genotypes calculated over the four successive stages of processing: NNN (r = 1.0); and nitrate (r = -0.9). NNK also correlated negatively with nicotine concentration changes (r = -0.9) in the low-alkaloid and high-alkaloid isolines during processing. After a 20-h incubation period under aerobic conditions followed by a 1-h standing period without aeration, substantial increases of NNK were observed in each burley line. The increased NNK contents ranged from 9-fold for the low-alkaloid isoline to 99-fold for the nornicotine-converter line. Increases in NNK content (27 to 69%) also occurred during the air drying stage; further increases occurred during a 15-month storage period at ambient conditions. After the HLC process and prolonged storage, maximal NNK contents were observed in each tobacco genotype in the following order of increasing NNK content: Ky 14 cultivar, 79 micrograms/g; low-alkaloid line, 80 micrograms/g; nornicotine converter line, 102 micrograms/g; and high-alkaloid line, 177 micrograms/g. At the beginning of a controlled environmental storage period used for high-alkaloid and low-alkaloid isoline air-cured and HLC tobaccos, NNK contents correlated with nitrite (r = 1.0) and nitrate (r = -0.9) calculated over the two curing regimens.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of storage conditions on nitrosated, acylated, and oxidized pyridine alkaloid derivatives in smokeless tobacco products.

Very large concentration increases in nitrite (34-fold), nitrosated pyridine alkaloids, and related 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (14- to 33-fold) occurred in moist snuff during storage at 24 degrees C for 52 weeks, whereas, decreases in all parent and some acylated pyridine alkaloids were observed in the same material. Nitrite concentrations in dry snuff decreased up to 90% during storage; increased contents of nitrosated alkaloids and NNK of 30 to 80% were also observed. Storage effects on chewing tobacco included a 75% increase in nitrite and small increases of nitrosated alkaloids and NNK. Sums of parent alkaloids in moist snuff decreased 24 and 54% after storage for 24 weeks at 24 and 32 degrees C, respectively, while sums of alkaloid derivatives increased, up to 36-fold for nitrosated alkaloids and NNK, 92% for acylated, and 133% for oxidized components. Levels of N'-nitrosonornicotine, NNK, and N'-nitrosoanatabine after 52 weeks' storage at 24 degrees C were 547, 41, and 296% higher, respectively, in ambient air-exposed moist snuff than in the nonexposed counterpart. A mathematical model was evaluated and used to calibrate nonlinear gas chromatography alkali bead detector response to the individual components. This permitted the use of a single analysis for all required individual compounds over a wide concentration range.

Perception of three-dimensional structure from motion.

The ability to perceive the 3-D shape of objects solely from motion cues is referred to as structure-from-motion perception. Recent experiments indicate how this remarkable perceptual attribute is computed by the brains of primates. This computation proceeds in at least two stages, one in which motion measurements are made and another in which moving surfaces are reconstructed. The middle temporal area (MT) in the macaque monkey appears to play a pivotal role in the latter step and suggests a previously unappreciated function for this well-known cortical region, which had previously been thought to play a more rudimentary role in simply signaling the direction of motion of images.

Cognitive neural prosthetics.

Research on neural prosthetics has focused largely on using activity related to hand trajectories recorded from motor cortical areas. An interesting question revolves around what other signals might be read out from the brain and used for neural prosthetic applications. Recent studies indicate that goals and expected value are among the high-level cognitive signals that can be used and will potentially enhance the ability of paralyzed patients to communicate with the outside world. Other new findings show that local field potentials provide an excellent source of information about the cognitive state of the subject and are much easier to record and maintain than spike activity. Finally, new movable probe technologies will enable recording electrodes to seek out automatically the best signals for decoding cognitive variables.

Isolation and characterization of hemolymph antifreeze proteins from larvae of the longhorn beetle Rhagium inquisitor (L.).

We describe a simple and effective procedure to isolate antifreeze proteins (AFPs) from the hemolymph of larvae of the longhorn beetle Rhagium inquisitor, and present some characteristics of their structures. Several AFPs were isolated from the hemolymph of this species by heat and acid extraction followed by cation exchange. The hemolymph contains at least six AFPs ranging in size from 12.5 to 12.8 kDa. Of these, three were separated to purity by the ion exchange step, as indicated by mass spectrometry. The remaining three forms were further separated by size exclusion chromatography, but could not be isolated to purity. All AFPs in the hemolymph of this species appears to have isoelectric points above 8.00. The dominant form, RiAFP(H4), was purified by the ion exchange step. Its amino acid composition reveals a lower level of cysteine and a higher level of threonine, arginine, alanine and glycine than seen in other insect AFPs. Its trypsin fingerprint does not match that of any known protein. It interacts with ice both in the anionic and cationic state.

Callosal and prefrontal associational projecting cell populations in area 7A of the macaque monkey: a study using retrogradely transported fluorescent dyes.

The spatial interrelationship of neurons in area 7a in the inferior parietal lobule that project through the corpus callosum to the corresponding field in the contralateral hemisphere or to the ipsilateral prefrontal cortex has been analyzed in macaque monkeys by using double-labeling procedures with retrogradely transported fluorescent dyes. The populations of callosal and associational projecting neurons have similar laminar distributions and are topographically intermingled. Less than 1% of the neurons were double-labeled, thus suggesting that the two populations are largely separate. Two-dimensional reconstructions of the distribution of labeled cells made on flattened reconstructions of the inferior parietal lobule revealed that the areal distribution of the two cortico-cortical output arrays is complex. Although each pattern of labeling showed some discontinuities in density, there was no obvious periodicity within or between the spatial distributions of the two projecting populations. It was consistently observed that the cortex of the lateral wall of the intraparietal sulcus, adjacent to area 7a, projects more heavily to the prefrontal cortex than does area 7a itself.