Publications by authors named "Alexander Kraskov"

35 Publications

Classification of Cortical Neurons by Spike Shape and the Identification of Pyramidal Neurons.

Cereb Cortex 2021 Jun 12. Epub 2021 Jun 12.

Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

Many investigators who make extracellular recordings from populations of cortical neurons are now using spike shape parameters, and particularly spike duration, as a means of classifying different neuronal sub-types. Because of the nature of the experimental approach, particularly that involving nonhuman primates, it is very difficult to validate directly which spike characteristics belong to particular types of pyramidal neurons and interneurons, as defined by modern histological approaches. This commentary looks at the way antidromic identification of pyramidal cells projecting to different targets, and in particular, pyramidal tract neurons (PTN), can inform the utility of spike width classification. Spike duration may provide clues to a diversity of function across the pyramidal cell population, and also highlights important differences that exist across species. Our studies suggest that further electrophysiological and optogenetic approaches are needed to validate spike duration as a means of cell classification and to relate this to well-established histological differences in neocortical cell types.
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http://dx.doi.org/10.1093/cercor/bhab147DOI Listing
June 2021

Pattern of paresis in ALS is consistent with the physiology of the corticomotoneuronal projections to different muscle groups.

J Neurol Neurosurg Psychiatry 2020 09 14;91(9):991-998. Epub 2020 Jul 14.

Department of Neurology, Clinical Neuroanatomy (Center for Biomedical Research), Ulm, Germany.

Objective: A recent neuroanatomical staging scheme of amyotrophic lateral sclerosis (ALS) indicates that a cortical lesion may spread, as a network disorder, both at the cortical level and via corticofugal tracts, including corticospinal projections providing direct monosynaptic input to α-motoneurons. These projections are involved preferentially and early in ALS. If these findings are clinically relevant, the pattern of paresis in ALS should primarily involve those muscle groups that receive the strongest direct corticomotoneuronal (CM) innervation.

Methods: In a large cohort (N=436), we analysed retrospectively the pattern of muscle paresis in patients with ALS using the UK Medical Research Council (MRC) scoring system; we subsequently carried out two independent prospective studies in two smaller groups (N=92 and N=54).

Results: The results indicated that a characteristic pattern of paresis exists. When pairs of muscle groups were compared within patients, the group known to receive the more pronounced CM connections was significantly weaker. Within patients, there was greater relative weakness (lower MRC score) in thumb abductors versus elbow extensors, for hand extensors versus hand flexors and for elbow flexors versus elbow extensors. In the lower limb, knee flexors were relatively weaker than extensors, and plantar extensors were weaker than plantar flexors.

Conclusions: These findings were mostly significant (p<0.01) for all six pairs of muscles tested and provide indirect support for the concept that ALS may specifically affect muscle groups with strong CM connections. This specific pattern could help to refine clinical and electrophysiological ALS diagnostic criteria and complement prospective clinicopathological correlation studies.
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http://dx.doi.org/10.1136/jnnp-2020-323331DOI Listing
September 2020

Movement initiation and grasp representation in premotor and primary motor cortex mirror neurons.

Elife 2020 07 6;9. Epub 2020 Jul 6.

Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, United Kingdom.

Pyramidal tract neurons (PTNs) within macaque rostral ventral premotor cortex (F5) and (M1) provide direct input to spinal circuitry and are critical for skilled movement control. Contrary to initial hypotheses, they can also be active during action observation, in the absence of any movement. A population-level understanding of this phenomenon is currently lacking. We recorded from single neurons, including identified PTNs, in (M1) (n = 187), and F5 (n = 115) as two adult male macaques executed, observed, or withheld (NoGo) reach-to-grasp actions. F5 maintained a similar representation of grasping actions during both execution and observation. In contrast, although many individual M1 neurons were active during observation, M1 population activity was distinct from execution, and more closely aligned to NoGo activity, suggesting this activity contributes to withholding of self-movement. M1 and its outputs may dissociate initiation of movement from representation of grasp in order to flexibly guide behaviour.
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http://dx.doi.org/10.7554/eLife.54139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384858PMC
July 2020

Starting and stopping movement by the primate brain.

Brain Neurosci Adv 2019 Jan-Dec;3:2398212819837149. Epub 2019 Mar 15.

Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London (UCL), London, UK.

We review the current knowledge about the part that motor cortex plays in the preparation and generation of movement, and we discuss the idea that corticospinal neurons, and particularly those with cortico-motoneuronal connections, act as 'command' neurons for skilled reach-to-grasp movements in the primate. We also review the increasing evidence that it is active during processes such as action observation and motor imagery. This leads to a discussion about how movement is inhibited and stopped, and the role in these for disfacilitation of the corticospinal output. We highlight the importance of the non-human primate as a model for the human motor system. Finally, we discuss the insights that recent research into the monkey motor system has provided for translational approaches to neurological diseases such as stroke, spinal injury and motor neuron disease.
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http://dx.doi.org/10.1177/2398212819837149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058194PMC
March 2019

Tractography-based parcellation does not provide strong evidence of anatomical organisation within the thalamus.

Neuroimage 2019 10 8;199:418-426. Epub 2019 Jun 8.

Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, University College London, London, United Kingdom. Electronic address:

Connectivity-based parcellation of subcortical structures using diffusion tractography is now a common paradigm in neuroscience. These analyses often imply voxel-level specificity of connectivity, and the formation of compact, spatially coherent clusters is often taken as strong imaging-based evidence for anatomically distinct subnuclei in an individual. In this study, we demonstrate that internal structure in diffusion anisotropy is not necessary for a plausible parcellation to be obtained, by spatially permuting diffusion parameters within the thalami and repeating the parcellation. Moreover, we show that, in a winner-takes-all paradigm, most voxels receive the same label before and after this shuffling process-a finding that is stable across image acquisitions and tractography algorithms. We therefore suggest that such parcellations should be interpreted with caution.
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http://dx.doi.org/10.1016/j.neuroimage.2019.06.019DOI Listing
October 2019

The Corticospinal Discrepancy: Where are all the Slow Pyramidal Tract Neurons?

Cereb Cortex 2019 08;29(9):3977-3981

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.

This feature article focuses on the discrepancy between the distribution of axon diameters within the primate corticospinal tract, determined neuroanatomically, and the distribution of axonal conduction velocities within the same tract, determined electrophysiologically. We point out the importance of resolving this discrepancy for a complete understanding of corticospinal functions, and discuss the various explanations for the mismatch between anatomy and physiology.
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http://dx.doi.org/10.1093/cercor/bhy278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896975PMC
August 2019

Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque.

J Comp Neurol 2017 Jun 14;525(9):2164-2174. Epub 2017 Mar 14.

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, United Kingdom.

There are substantial differences across species in the organization and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration "thin" spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the Kv3.1b expression in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labeled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, and lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium, and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons.
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http://dx.doi.org/10.1002/cne.24192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413836PMC
June 2017

Scene-selective coding by single neurons in the human parahippocampal cortex.

Proc Natl Acad Sci U S A 2017 01 17;114(5):1153-1158. Epub 2017 Jan 17.

Department of Neurosurgery and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095.

Imaging, electrophysiological, and lesion studies have shown a relationship between the parahippocampal cortex (PHC) and the processing of spatial scenes. Our present knowledge of PHC, however, is restricted to the macroscopic properties and dynamics of bulk tissue; the behavior and selectivity of single parahippocampal neurons remains largely unknown. In this study, we analyzed responses from 630 parahippocampal neurons in 24 neurosurgical patients during visual stimulus presentation. We found a spatially clustered subpopulation of scene-selective units with an associated event-related field potential. These units form a population code that is more distributed for scenes than for other stimulus categories, and less sparse than elsewhere in the medial temporal lobe. Our electrophysiological findings provide insight into how individual units give rise to the population response observed with functional imaging in the parahippocampal place area.
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http://dx.doi.org/10.1073/pnas.1608159113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293078PMC
January 2017

Modulation of the Intracortical LFP during Action Execution and Observation.

J Neurosci 2015 Jun;35(22):8451-61

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London WC1N 3BG, United Kingdom.

The activity of mirror neurons in macaque ventral premotor cortex (PMv) and primary motor cortex (M1) is modulated by the observation of another's movements. This modulation could underpin well documented changes in EEG/MEG activity indicating the existence of a mirror neuron system in humans. Because the local field potential (LFP) represents an important link between macaque single neuron and human noninvasive studies, we focused on mirror properties of intracortical LFPs recorded in the PMv and M1 hand regions in two macaques while they reached, grasped and held different objects, or observed the same actions performed by an experimenter. Upper limb EMGs were recorded to control for covert muscle activity during observation.The movement-related potential (MRP), investigated as intracortical low-frequency LFP activity (<9 Hz), was modulated in both M1 and PMv, not only during action execution but also during action observation. Moreover, the temporal LFP modulations during execution and observation were highly correlated in both cortical areas. Beta power in both PMv and M1 was clearly modulated in both conditions. Although the MRP was detected only during dynamic periods of the task (reach/grasp/release), beta decreased during dynamic and increased during static periods (hold).Comparison of LFPs for different grasps provided evidence for partially nonoverlapping networks being active during execution and observation, which might be related to different inputs to motor areas during these conditions. We found substantial information about grasp in the MRP corroborating its suitability for brain-machine interfaces, although information about grasp was generally low during action observation.
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http://dx.doi.org/10.1523/JNEUROSCI.5137-14.2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452553PMC
June 2015

Single-cell responses to face adaptation in the human medial temporal lobe.

Neuron 2014 Oct 25;84(2):363-9. Epub 2014 Sep 25.

Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA; Allen Institute for Brain Science, Seattle, WA 98103, USA.

We used a face adaptation paradigm to bias the perception of ambiguous images of faces and study how single neurons in the human medial temporal lobe (MTL) respond to the same images eliciting different percepts. The ambiguous images were morphs between the faces of two familiar individuals, chosen because at least one MTL neuron responded selectively to one but not to the other face. We found that the firing of MTL neurons closely followed the subjects' perceptual decisions--i.e., recognizing one person or the other. In most cases, the response to the ambiguous images was similar to the one obtained when showing the pictures without morphing. Altogether, these results show that many neurons in the medial temporal lobe signal the subjects' perceptual decisions rather than the visual features of the stimulus.
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http://dx.doi.org/10.1016/j.neuron.2014.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210637PMC
October 2014

Influence of spiking activity on cortical local field potentials.

J Physiol 2013 Nov 27;591(21):5291-303. Epub 2013 Aug 27.

S. Waldert: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London WC1N 3BG, UK.

The intra-cortical local field potential (LFP) reflects a variety of electrophysiological processes including synaptic inputs to neurons and their spiking activity. It is still a common assumption that removing high frequencies, often above 300 Hz, is sufficient to exclude spiking activity from LFP activity prior to analysis. Conclusions based on such supposedly spike-free LFPs can result in false interpretations of neurophysiological processes and erroneous correlations between LFPs and behaviour or spiking activity. Such findings might simply arise from spike contamination rather than from genuine changes in synaptic input activity. Although the subject of recent studies, the extent of LFP contamination by spikes is unclear, and the fundamental problem remains. Using spikes recorded in the motor cortex of the awake monkey, we investigated how different factors, including spike amplitude, duration and firing rate, together with the noise statistic, can determine the extent to which spikes contaminate intra-cortical LFPs. We demonstrate that such contamination is realistic for LFPs with a frequency down to ∼10 Hz. For LFP activity below ∼10 Hz, such as movement-related potential, contamination is theoretically possible but unlikely in real situations. Importantly, LFP frequencies up to the (high-) gamma band can remain unaffected. This study shows that spike-LFP crosstalk in intra-cortical recordings should be assessed for each individual dataset to ensure that conclusions based on LFP analysis are valid. To this end, we introduce a method to detect and to visualise spike contamination, and provide a systematic guide to assess spike contamination of intra-cortical LFPs.
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http://dx.doi.org/10.1113/jphysiol.2013.258228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3936368PMC
November 2013

M1 corticospinal mirror neurons and their role in movement suppression during action observation.

Curr Biol 2013 Feb 3;23(3):236-43. Epub 2013 Jan 3.

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.

Evidence is accumulating that neurons in primary motor cortex (M1) respond during action observation, a property first shown for mirror neurons in monkey premotor cortex. We now show for the first time that the discharge of a major class of M1 output neuron, the pyramidal tract neuron (PTN), is modulated during observation of precision grip by a human experimenter. We recorded 132 PTNs in the hand area of two adult macaques, of which 65 (49%) showed mirror-like activity. Many (38 of 65) increased their discharge during observation (facilitation-type mirror neuron), but a substantial number (27 of 65) exhibited reduced discharge or stopped firing (suppression-type). Simultaneous recordings from arm, hand, and digit muscles confirmed the complete absence of detectable muscle activity during observation. We compared the discharge of the same population of neurons during active grasp by the monkeys. We found that facilitation neurons were only half as active for action observation as for action execution, and that suppression neurons reversed their activity pattern and were actually facilitated during execution. Thus, although many M1 output neurons are active during action observation, M1 direct input to spinal circuitry is either reduced or abolished and may not be sufficient to produce overt muscle activity.
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http://dx.doi.org/10.1016/j.cub.2012.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566480PMC
February 2013

The activity of primary motor cortex corticospinal neurons during tool use by macaque monkeys.

J Neurosci 2012 Nov;32(48):17351-64

Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, London WC1N 3BG, United Kingdom.

It has been suggested that the distinctive capacity of some nonhuman primates to use tools may reflect a well-developed corticospinal system and, in particular, direct cortico-motoneuronal (CM) connections to hand muscles. We investigated the activity of corticospinal neurons in the primary motor cortex hand area during the use of a tool by two adult macaque monkeys. They used a light rake to retrieve food rewards placed in their extrapersonal space. An analysis of EMG activity showed that the rake task involved a complex interaction of muscles acting on the digits, hand, and arm. Sixty-nine corticospinal neurons were identified antidromically as pyramidal tract neurons (PTNs). When tested on the rake task, most (64 of 69; 93%) showed a significant modulation of their discharge during at least one of three task periods: grasping the rake, projecting it beyond the food reward, and then pulling it back to retrieve the reward. Discharge patterns were heterogeneous, and many PTNs showed significant suppression of discharge during raking. Seventeen of the 69 PTNs recorded during the rake task were further identified as CM cells, exerting clear postspike facilitation on digit muscles, demonstrating that the CM system contributes to the skilled use of tools. We compared the activity of each PTN on the rake task with that during precision grip. Most PTNs (90%) modulated their activity significantly for both tasks, demonstrating that PTNs activated by a task involving fractionated movements of the digits are also recruited during rake use, although there were often contrasting patterns of PTN recruitment and muscle activity for the two tasks.
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http://dx.doi.org/10.1523/JNEUROSCI.1009-12.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678117PMC
November 2012

The role of inhibition in action observation treatment.

Dev Med Child Neurol 2012 Sep 5;54(9):778. Epub 2012 Jul 5.

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK.

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http://dx.doi.org/10.1111/j.1469-8749.2012.04356.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467763PMC
September 2012

Large identified pyramidal cells in macaque motor and premotor cortex exhibit "thin spikes": implications for cell type classification.

J Neurosci 2011 Oct;31(40):14235-42

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London WC1N 3BG, United Kingdom.

Recent studies have suggested that extracellular recordings of putative cortical interneurons have briefer spikes than those of pyramidal neurons, providing a means of identifying cortical cell types in recordings from awake monkeys. To test this, we investigated the spike duration of antidromically identified pyramidal tract neurons (PTNs) recorded from primary motor (M1) or ventral premotor cortex (area F5) in 4 awake macaque monkeys. M1 antidromic latencies (ADLs) were skewed toward short ADLs (151 PTNs; 0.5-5.5 ms, median 1.1 ms) and significantly different from that of F5 ADLs (54 PTNs; 1.0-6.9 ms, median 2.6 ms). The duration of PTN spikes, recorded with a high-pass filter of 300 Hz and measured from the negative trough to the positive peak of the spike waveform, ranged from 0.15 to 0.71 ms. Importantly, we found a positive linear correlation between ADL and spike duration in both M1 (R(2) = 0.40, p < 0.001) and F5 (R(2) = 0.57, p < 0.001). Thus PTNs with the shortest ADL (fastest axons) had the briefest spikes, and since PTN soma size is correlated with axon size and conduction velocity, it is likely that the largest pyramidal neurons (Betz cells in M1) have spikes with short durations (0.15-0.45 ms), which overlap heavily with those reported for putative interneurons in previous studies in non-primates. In summary, one class of physiologically identified cortical pyramidal neuron exhibits a wide variety of spike durations and the results suggest that spike duration alone may not be a reliable indicator of cell type.
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http://dx.doi.org/10.1523/JNEUROSCI.3142-11.2011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199219PMC
October 2011

A category-specific response to animals in the right human amygdala.

Nat Neurosci 2011 Aug 28;14(10):1247-9. Epub 2011 Aug 28.

Division of Biology, California Institute of Technology, Pasadena, California, USA.

The amygdala is important in emotion, but it remains unknown whether it is specialized for certain stimulus categories. We analyzed responses recorded from 489 single neurons in the amygdalae of 41 neurosurgical patients and found a categorical selectivity for pictures of animals in the right amygdala. This selectivity appeared to be independent of emotional valence or arousal and may reflect the importance that animals held throughout our evolutionary past.
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http://dx.doi.org/10.1038/nn.2899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505687PMC
August 2011

Interactions between areas of the cortical grasping network.

Curr Opin Neurobiol 2011 Aug 21;21(4):565-70. Epub 2011 Jun 21.

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, WC1N 3BG, London, UK.

Skilled grasp is a sensorimotor process requiring the brain to extract sensory cues from the environment to shape a motor command. Although a large body of literature has focused on which brain areas either integrate the visual object's properties or control the motor output, it is still unclear how grasp-related information is transferred from one area to another. Understanding interactions between brain areas is crucial for the study of visuomotor transformations. Recently, new advances in both human and non-human primates have shown it is possible to study cortico-cortical interactions during different task contexts. This sheds new light on how brain areas are integrated in a dynamic network for controlling grasping actions.
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http://dx.doi.org/10.1016/j.conb.2011.05.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437559PMC
August 2011

Ventral premotor-motor cortex interactions in the macaque monkey during grasp: response of single neurons to intracortical microstimulation.

J Neurosci 2011 Jun;31(24):8812-21

Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, UCL, London WC1N 3BG, United Kingdom.

Recent stimulation studies in monkeys and humans have shown strong interactions between ventral premotor cortex (area F5) and the hand area of primary motor cortex (M1). These short-latency interactions usually involve facilitation from F5 of M1 outputs to hand muscles, although suppression has also been reported. This study, performed in three awake macaque monkeys, sought evidence that these interactions could be mediated by short-latency excitatory and inhibitory responses of single M1 neurons active during grasping tasks. We recorded responses of these M1 neurons to single low-threshold (≤40 μA) intracortical microstimuli delivered to F5 sites at which grasp-related neurons were recorded. In 29 sessions, we tested 232 M1 neurons with stimuli delivered to between one and four sites in F5. Of the 415 responses recorded, 142 (34%) showed significant effects. The most common type of response was pure excitation (53% of responses), with short latency (1.8-3.0 ms) and brief duration (∼1 ms); purely inhibitory responses had slightly longer latencies (2-5 ms) and were of small amplitude and longer duration (5-7 ms). They accounted for 13% of responses, whereas mixed excitation then inhibition was seen in 34%. Remarkably, a rather similar set of findings applied to 280 responses of 138 F5 neurons to M1 stimulation; 109 (34%) responses showed significant effects. Thus, with low-intensity stimuli, the dominant interaction between these two cortical areas is one of short-latency, brief excitation, most likely mediated by reciprocal F5-M1 connections. Some neurons were tested with stimuli at both 20 and 40 μA; inhibition tended to dominate at the higher intensity.
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http://dx.doi.org/10.1523/JNEUROSCI.0525-11.2011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121557PMC
June 2011

On-line, voluntary control of human temporal lobe neurons.

Nature 2010 Oct;467(7319):1104-8

Computation and Neural Systems, California Institute of Technology, Pasadena, California 91125, USA.

Daily life continually confronts us with an exuberance of external, sensory stimuli competing with a rich stream of internal deliberations, plans and ruminations. The brain must select one or more of these for further processing. How this competition is resolved across multiple sensory and cognitive regions is not known; nor is it clear how internal thoughts and attention regulate this competition. Recording from single neurons in patients implanted with intracranial electrodes for clinical reasons, here we demonstrate that humans can regulate the activity of their neurons in the medial temporal lobe (MTL) to alter the outcome of the contest between external images and their internal representation. Subjects looked at a hybrid superposition of two images representing familiar individuals, landmarks, objects or animals and had to enhance one image at the expense of the other, competing one. Simultaneously, the spiking activity of their MTL neurons in different subregions and hemispheres was decoded in real time to control the content of the hybrid. Subjects reliably regulated, often on the first trial, the firing rate of their neurons, increasing the rate of some while simultaneously decreasing the rate of others. They did so by focusing onto one image, which gradually became clearer on the computer screen in front of their eyes, and thereby overriding sensory input. On the basis of the firing of these MTL neurons, the dynamics of the competition between visual images in the subject's mind was visualized on an external display.
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http://dx.doi.org/10.1038/nature09510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010923PMC
October 2010

Corticospinal neurons in macaque ventral premotor cortex with mirror properties: a potential mechanism for action suppression?

Neuron 2009 Dec;64(6):922-30

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London WC1N3BG, UK.

The discovery of "mirror neurons" in area F5 of the ventral premotor cortex has prompted many theories as to their possible function. However, the identity of mirror neurons remains unknown. Here, we investigated whether identified pyramidal tract neurons (PTNs) in area F5 of two adult macaques exhibited "mirror-like" activity. About half of the 64 PTNs tested showed significant modulation of their activity while monkeys observed precision grip of an object carried out by an experimenter, with somewhat fewer showing modulation during precision grip without an object or grasping concealed from the monkey. Therefore, mirror-like activity can be transmitted directly to the spinal cord via PTNs. A novel finding is that many PTNs (17/64) showed complete suppression of discharge during action observation, while firing actively when the monkey grasped food rewards. We speculate that this suppression of PTN discharge might be involved in the inhibition of self-movement during action observation.
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http://dx.doi.org/10.1016/j.neuron.2009.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862290PMC
December 2009

Responses of human medial temporal lobe neurons are modulated by stimulus repetition.

J Neurophysiol 2010 Jan 28;103(1):97-107. Epub 2009 Oct 28.

Department of Engineering, University of Leicester, Leicester, UK.

Recent studies have reported the presence of single neurons with strong responses to visual inputs in the human medial temporal lobe. Here we show how repeated stimulus presentation--photos of celebrities and familiar individuals, landmark buildings, animals, and objects--modulates the firing rate of these cells: a consistent decrease in the neural activity was registered as images were repeatedly shown during experimental sessions. The effect of repeated stimulus presentation was not the same for all medial temporal lobe areas. These findings are consistent with the view that medial temporal lobe neurons link visual percepts to declarative memory.
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http://dx.doi.org/10.1152/jn.91323.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807242PMC
January 2010

Explicit encoding of multimodal percepts by single neurons in the human brain.

Curr Biol 2009 Aug 23;19(15):1308-13. Epub 2009 Jul 23.

Department of Engineering, University of Leicester, LE1 7RH Leicester, UK.

Different pictures of Marilyn Monroe can evoke the same percept, even if greatly modified as in Andy Warhol's famous portraits. But how does the brain recognize highly variable pictures as the same percept? Various studies have provided insights into how visual information is processed along the "ventral pathway," via both single-cell recordings in monkeys and functional imaging in humans. Interestingly, in humans, the same "concept" of Marilyn Monroe can be evoked with other stimulus modalities, for instance by hearing or reading her name. Brain imaging studies have identified cortical areas selective to voices and visual word forms. However, how visual, text, and sound information can elicit a unique percept is still largely unknown. By using presentations of pictures and of spoken and written names, we show that (1) single neurons in the human medial temporal lobe (MTL) respond selectively to representations of the same individual across different sensory modalities; (2) the degree of multimodal invariance increases along the hierarchical structure within the MTL; and (3) such neuronal representations can be generated within less than a day or two. These results demonstrate that single neurons can encode percepts in an explicit, selective, and invariant manner, even if evoked by different sensory modalities.
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http://dx.doi.org/10.1016/j.cub.2009.06.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032396PMC
August 2009

Selectivity for grasp in local field potential and single neuron activity recorded simultaneously from M1 and F5 in the awake macaque monkey.

J Neurosci 2008 Oct;28(43):10961-71

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London WC1N3BG, United Kingdom.

The selectivity for object-specific grasp in local field potentials (LFPs) was investigated in two awake macaque monkeys trained to observe, reach out, grasp and hold one of six objects presented in a pseudorandom order. Simultaneous, multiple electrode recordings were made from the hand representations of primary motor cortex (M1) and ventral premotor cortex (area F5). LFP activity was well developed during the observation and hold periods of the task, especially in the beta-frequency range (15-30 Hz). Selectivity of LFP activity for upcoming grasp was rare in the observation period, but common during stable grasp. The majority of M1 (90 of 92) and F5 (81 of 97) sites showed selectivity for at least one frequency, which was maximal in the beta range but also present at higher frequencies (30-50 Hz). When the LFP power associated with grasp of a specific object was large in the beta-frequency range, it was usually of low power in the higher 30-50 Hz range, and vice-versa. Simple hook grips involving flexion of one or more fingers were associated with large beta power, whereas more complex grips involving the thumb (e.g., precision grip) were associated with small beta power. At many M1 sites, there was a highly significant inverse relationship between the tuning of spikes (including those of identified pyramidal tract neurons) and beta-range LFP for different grasps, whereas a positive correlation was found at higher frequencies (30-50 Hz). High levels of beta LFP and low pyramidal cell spike rate may reflect a common mechanism used to control motor set during different types of grasp.
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http://dx.doi.org/10.1523/JNEUROSCI.1956-08.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637078PMC
October 2008

Latency and selectivity of single neurons indicate hierarchical processing in the human medial temporal lobe.

J Neurosci 2008 Sep;28(36):8865-72

Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.

Neurons in the temporal lobe of both monkeys and humans show selective responses to classes of visual stimuli and even to specific individuals. In this study, we investigate the latency and selectivity of visually responsive neurons recorded from microelectrodes in the parahippocampal cortex, entorhinal cortex, hippocampus, and amygdala of human subjects during a visual object presentation task. During 96 experimental sessions in 35 subjects, we recorded from a total of 3278 neurons. Of these units, 398 responded selectively to one or more of the presented stimuli. Mean response latencies were substantially larger than those reported in monkeys. We observed a highly significant correlation between the latency and the selectivity of these neurons: the longer the latency the greater the selectivity. Particularly, parahippocampal neurons were found to respond significantly earlier and less selectively than those in the other three regions. Regional analysis showed significant correlations between latency and selectivity within the parahippocampal cortex, entorhinal cortex, and hippocampus, but not within the amygdala. The later and more selective responses tended to be generated by cells with sparse baseline firing rates and vice versa. Our results provide direct evidence for hierarchical processing of sensory information at the interface between the visual pathway and the limbic system, by which increasingly refined and specific representations of stimulus identity are generated over time along the anatomic pathways of the medial temporal lobe.
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http://dx.doi.org/10.1523/JNEUROSCI.1640-08.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676868PMC
September 2008

Local field potentials and spikes in the human medial temporal lobe are selective to image category.

J Cogn Neurosci 2007 Mar;19(3):479-92

California Institute of Technology, California, USA.

Local field potentials (LFPs) reflect the averaged dendrosomatic activity of synaptic signals of large neuronal populations. In this study, we investigate the selectivity of LFPs and single neuron activity to semantic categories of visual stimuli in the medial temporal lobe of nine neurosurgical patients implanted with intracranial depth electrodes for clinical reasons. Strong selectivity to the category of presented images was found for the amplitude of LFPs in 8% of implanted microelectrodes and for the firing rates of single and multiunits in 14% of microelectrodes. There was little overlap between the LFP- and spike-selective microelectrodes. Separate analysis of the power and phase of LFPs revealed that the mean phase was category-selective around the theta frequency range and that the power of the LFPs was category-selective for high frequencies around the gamma rhythm. Of the 36 microelectrodes with amplitude-selective LFPs, 30 were found in the hippocampus. Finally, it was possible to readout information about the category of stimuli presented to the patients with both spikes and LFPs. Combining spiking and LFP activity enhanced the decoding accuracy in comparison with the accuracy obtained with each signal alone, especially for short time intervals.
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http://dx.doi.org/10.1162/jocn.2007.19.3.479DOI Listing
March 2007

Sparse representation in the human medial temporal lobe.

J Neurosci 2006 Oct;26(40):10232-4

Control and Dynamical Systems, California Institute of Technology, Pasadena, California 91125, USA.

Recent experiments characterized individual neurons in the human medial temporal lobe with remarkably selective, invariant, and explicit responses to images of famous individuals or landmark buildings. Here, we used a probabilistic analysis to show that these data are consistent with a sparse code in which neurons respond in a selective manner to a small fraction of stimuli.
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http://dx.doi.org/10.1523/JNEUROSCI.2101-06.2006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6674629PMC
October 2006

Monte Carlo algorithm for least dependent non-negative mixture decomposition.

Anal Chem 2006 Mar;78(5):1620-7

John von Neumann Institute for Computing, Forschungszentrum Jülich, D-52425, Jülich, Germany.

We propose a simulated annealing algorithm (stochastic non-negative independent component analysis, SNICA) for blind decomposition of linear mixtures of non-negative sources with non-negative coefficients. The demixing is based on a Metropolis-type Monte Carlo search for least dependent components, with the mutual information between recovered components as a cost function and their non-negativity as a hard constraint. Elementary moves are shears in two-dimensional subspaces and rotations in three-dimensional subspaces. The algorithm is geared at decomposing signals whose probability densities peak at zero, the case typical in analytical spectroscopy and multivariate curve resolution. The decomposition performance on large samples of synthetic mixtures and experimental data is much better than that of traditional blind source separation methods based on principal component analysis (MILCA, FastICA, RADICAL) and chemometrics techniques (SIMPLISMA, ALS, BTEM).
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http://dx.doi.org/10.1021/ac051707cDOI Listing
March 2006

Object selectivity of local field potentials and spikes in the macaque inferior temporal cortex.

Neuron 2006 Feb;49(3):433-45

McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Local field potentials (LFPs) arise largely from dendritic activity over large brain regions and thus provide a measure of the input to and local processing within an area. We characterized LFPs and their relationship to spikes (multi and single unit) in monkey inferior temporal cortex (IT). LFP responses in IT to complex objects showed strong selectivity at 44% of the sites and tolerance to retinal position and size. The LFP preferences were poorly predicted by the spike preferences at the same site but were better explained by averaging spikes within approximately 3 mm. A comparison of separate sites suggests that selectivity is similar on a scale of approximately 800 microm for spikes and approximately 5 mm for LFPs. These observations imply that inputs to IT neurons convey selectivity for complex shapes and that such input may have an underlying organization spanning several millimeters.
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http://dx.doi.org/10.1016/j.neuron.2005.12.019DOI Listing
February 2006

On the predictability of epileptic seizures.

Clin Neurophysiol 2005 Mar 6;116(3):569-87. Epub 2005 Jan 6.

Department of Epileptology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.

Objective: An important issue in epileptology is the question whether information extracted from the EEG of epilepsy patients can be used for the prediction of seizures. Several studies have claimed evidence for the existence of a pre-seizure state that can be detected using different characterizing measures. In this paper, we evaluate the predictability of seizures by comparing the predictive performance of a variety of univariate and bivariate measures comprising both linear and non-linear approaches.

Methods: We compared 30 measures in terms of their ability to distinguish between the interictal period and the pre-seizure period. After completely analyzing continuous inctracranial multi-channel recordings from five patients lasting over days, we used ROC curves to distinguish between the amplitude distributions of interictal and preictal time profiles calculated for the respective measures. We compared different evaluation schemes including channelwise and seizurewise analysis plus constant and adaptive reference levels. Particular emphasis was placed on statistical validity and significance.

Results: Univariate measures showed statistically significant performance only in a channelwise, seizurewise analysis using an adaptive baseline. Preictal changes for these measures occurred 5-30 min before seizures. Bivariate measures exhibited high performance values reaching statistical significance for a channelwise analysis using a constant baseline. Preictal changes were found at least 240 min before seizures. Linear measures were found to perform similar or better than non-linear measures.

Conclusions: Results provide statistically significant evidence for the existence of a preictal state. Based on our findings, the most promising approach for prospective seizure anticipation could be a combination of bivariate and univariate measures.

Significance: Many measures reported capable of seizure prediction in earlier studies are found to be insignificant in performance, which underlines the need for statistical validation in this field.
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http://dx.doi.org/10.1016/j.clinph.2004.08.025DOI Listing
March 2005

Least-dependent-component analysis based on mutual information.

Phys Rev E Stat Nonlin Soft Matter Phys 2004 Dec 13;70(6 Pt 2):066123. Epub 2004 Dec 13.

John-von-Neumann Institute for Computing, Forschungszentrum Jülich, D-52425 Jülich, Germany.

We propose to use precise estimators of mutual information (MI) to find the least dependent components in a linearly mixed signal. On the one hand, this seems to lead to better blind source separation than with any other presently available algorithm. On the other hand, it has the advantage, compared to other implementations of "independent" component analysis (ICA), some of which are based on crude approximations for MI, that the numerical values of the MI can be used for (i) estimating residual dependencies between the output components; (ii) estimating the reliability of the output by comparing the pairwise MIs with those of remixed components; and (iii) clustering the output according to the residual interdependencies. For the MI estimator, we use a recently proposed k -nearest-neighbor-based algorithm. For time sequences, we combine this with delay embedding, in order to take into account nontrivial time correlations. After several tests with artificial data, we apply the resulting MILCA (mutual-information-based least dependent component analysis) algorithm to a real-world dataset, the ECG of a pregnant woman.
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http://dx.doi.org/10.1103/PhysRevE.70.066123DOI Listing
December 2004
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