Biology subjects

Jacobs, J.

Publications and source records attributed to Jacobs, J..

67 records · Page 4Linked to original sources

bioRxiv2019

The effects of direct brain stimulation in humans depend on frequency, amplitude, and white-matter proximity.

Researchers have used direct electrical brain stimulation to treat a range of neurological and psychiatric disorders. However, for brain stimulation to be maximally effective, clinicians and researchers should optimize stimulation parameters according to desired outcomes. To examine how different kinds of stimulation affect human brain activity, we compared the changes in neuronal activity that resulted from stimulation at a range of frequencies, amplitudes, and locations with direct human brain recordings. We recorded human brain activity directly with electrodes that were implanted in widespread regions across 106 neurosurgical epilepsy patients while systematically stimulating across a range of parameters and locations. Overall, stimulation most often had an inhibitory effect on neuronal activity, consistent with earlier work. When stimulation excited neuronal activity, it most often occurred from high-frequency stimulation. These effects were modulated by the location of the stimulating electrode, with stimulation sites near white matter more likely to cause excitation and sites near gray matter more likely to inhibit neuronal activity. By characterizing how different stimulation parameters produced specific neuronal activity patterns on a large scale, our results help guide clinicians and researchers when designing stimulation protocols to cause precisely targeted changes in human brain activity.

neuroscience↗

bioRxiv2019

Genotyping-by-sequencing based cytoplasmic markers underpin population structural variation of perennial ryegrass

Chloroplast and mitochondrial genomes provide unique information in studying plant populations because cytoplasmic genes exhibit a different mode of inheritance and a different rate of gene mutation compared to nuclear genes. Despite this, cytoplasmic genomic contributions to plant population performance are largely unexplored because few methods are available to characterize and evaluate cytoplasmic genome-wide variations. Here we have developed cytoplasmic markers based on genotyping-by-sequencing (GBS), which enable us to characterize thousands of samples, to survey gene variants across cytoplasmic genomes, and to monitor within-population variations of chloroplast or mitochondrial origin. Using these cytoplasmic genome-wide markers we have found that within-population differentiations are evident in ryegrass (Lolium perenne), beyond the explanation of nuclear markers. Moreover, chloroplast and mitochondrial variations exhibit different patterns, with mitochondrial markers more readily reflecting the maternal origins. Application of GBS-based cytoplasmic markers should facilitate quantifying the contribution of cytoplasmic inheritance to plant performance through selective breeding or under natural selection pressure.

genetics↗

bioRxiv2019

Intracranial EEG reveals bihemispheric parietal and extra parietal brain networks supporting mental arithmetic

Mathematical reasoning is central to everyday life. Lesion data and functional MRI studies suggest that even simple arithmetic involves the coordination of multiple spatially diverse brain regions, but to date, math processing has not been well characterized using direct brain recordings, especially outside of the parietal cortex. To address this, we utilized an unparalleled data set of 310 subjects implanted with intracranial electrodes to investigate the spatial and temporal dynamics of arithmetic reasoning. Our data support the importance of regions previously implicated in numerosity such as the superior parietal lobule and intraparietal sulcus. However, we also identify contributions to arithmetic processing from regions such as the entorhinal cortex and temporal pole. Using the excellent bihemispheric coverage afforded by our data set and the precise temporal resolution of intracranial recordings, we characterize in detail the spatial and temporal characteristics of an arithmetic processing network, quantifying subtle hemispheric differences for selected regions. We also examine how activity in these regions predicts arithmetic ability and look for gender differences in the pattern of network activation. Our findings further define the complex network of regions involved in human arithmetical reasoning.

neuroscience↗

bioRxiv2019

A natural, conditional gene drive in plants

A new class of gene drive in plant populations with herbicide resistance is described; a conditional gene drive that operates following herbicide application. Screening progeny from controlled crosses of Brassica napus heterozygous for a dominant allele conferring chlorsulfuron resistance, demonstrated that the herbicide imposes in planta gametic selection against pollen and ovules with the recessive allele for herbicide susceptibility, as well as embryonic selection against embryos homozygous for the susceptible allele. We postulate that natural gene drives are common in plant populations and can operate in a conditional manner resulting in non-Mendelian inheritance in response to abiotic and biotic stresses.

plant biology↗

bioRxiv2019

Single-neuron representations of spatial memory targets in humans

The hippocampus and surrounding medial-temporal-lobe (MTL) structures are critical for both memory and spatial navigation, but we do not fully understand the neuronal representations used to support these behaviors. Much research has examined how the MTL neurally represents spatial information, such as with \"place cells\" that represent the current location or \"head-direction cells\" that code for the current heading. In addition to behaviors that require an animal to attend to the current spatial location, navigating to remote destinations is a common part of daily life. To examine the neural basis of these behaviors we recorded single-neuron activity from neurosurgical patients playing Treasure Hunt, a virtual-reality spatial-memory task. By analyzing how the activity of these neurons related to behavior in Treasure Hunt, we found that the firing rates of many MTL neurons during navigation significantly changed depending on the position of the current spatial target. In addition, we observed neurons whose firing rates during navigation were tuned to specific heading directions in the environment, and others whose activity changed depending on the timing within the trial. By showing that neurons in our task represent remote locations rather than the subjects own position, our results suggest that the human MTL can represent remote spatial information according to task demands.

neuroscience↗

bioRxiv2018

Functionally distinct high and low theta oscillations in the human hippocampus

Based on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4-10-Hz rhythm that coordinates brain-wide neural activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in thetas function. To characterize human hippocampal theta, we examined the properties of theta oscillations throughout the anterior-posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observed hippocampal oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus prominently displayed oscillations at ~8-Hz and the precise frequency of these oscillations correlated with the speed of movement, implicating these signals in spatial navigation. We also observed slower ~3-Hz oscillations, but these signals were more prevalent in the anterior hippocampus and their frequency did not vary with movement speed. Our results converge with recent findings to suggest an updated view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a single general role, high-and low-theta oscillations, respectively, may reflect spatial and non-spatial cognitive processes.

neuroscience↗

bioRxiv2018

Single neurons in the human entorhinal cortex remap to distinguish individual spatial memories

The entorhinal cortex (EC) is known to play a key role in both memory and spatial navigation. Despite this overlap in spatial and mnemonic circuits, it is unknown how spatially responsive neurons contribute to our ability to represent and distinguish past experiences. Recording from medial temporal lobe (MTL) neurons in subjects performing cued recall of object-location memories in a virtual-reality environment, we identified \"trace cells\" in the EC that remap their spatial fields to locations subjects were cued to recall on each trial. In addition to shifting its firing field according to the memory cue, this neuronal activity exhibited a firing rate predictive of the cued memorys content. Critically, this memory-specific neuronal activity re-emerged when subjects were cued for recall without entering the environment, indicating that trace-cell memory representations generalized beyond navigation. These findings suggest a general mechanism for memory retrieval via trace-cell activity and remapping in the EC.

neuroscience↗

bioRxiv2018

Spatial and temporal locomotor learning in mouse cerebellum

Stable and efficient locomotion requires precise coordination of whole-body movements. Learned changes in interlimb coordination can be induced by exposure to a split-belt treadmill that imposes different speeds under each side of the body. Here we show that mice adapt to split-belt walking in a way that is remarkably similar to humans, suggesting that this form of locomotor learning is highly conserved across vertebrates. Like human learning, mouse locomotor adaptation is specific to measures of interlimb coordination, has spatial and temporal components that adapt at different rates, and is highly context-specific. Using a variety of approaches, we demonstrate that split-belt adaptation in mice specifically depends on intermediate cerebellum, but is insensitive to large lesions of cerebral cortex. Finally, cell-type specific chemogenetics combined with quantitative behavioral analysis reveal distinct neural circuit mechanisms underlying spatial vs. temporal components of locomotor adaptation.

neuroscience↗

bioRxiv2017

Electrophysiological signatures of spatial boundaries in the human subiculum

Environmental boundaries play a crucial role in spatial navigation and memory across a wide range of distantly-related species. In rodents, boundary representations have been identified at the single-cell level in the subiculum and entorhinal cortex of the hippocampal formation. While studies of hippocampal function and spatial behavior suggest that similar representations might exist in humans, boundary-related neural activity has not been identified electrophysiologically in humans until now. Here we present direct intracranial recordings from the hippocampal formation of surgical epilepsy patients while they performed a virtual spatial navigation task. Our results suggest that encoding target locations near boundaries elicited stronger theta oscillations than for target locations near the center of the environment and that this difference cannot be explained by variables such as trial length, speed, or movement. These findings provide the first direct evidence of boundary-dependent neural activity localized in humans to the subiculum, the homologue of the hippocampal subregion in which most rodent boundary cells are found.\n\nSignificance StatementSpatial computations using environmental boundaries are an integral part of the brains spatial mapping system. In rodents, border/boundary cells in the subiculum and entorhinal cortex reveal boundary coding at the single-neuron level. Although there is good reason to believe that such representations also exist in humans, the evidence has thus far been limited to fMRI studies that broadly implicate the hippocampus in boundary-based navigation. By combining intracranial recordings with high-resolution imaging of hippocampal subregions we identified, for the first time in humans, a neural marker of boundary representation in the subiculum.

neuroscience↗

bioRxiv2017

Theta and alpha oscillations are traveling waves in the human neocortex

Human cognition requires the coordination of neural activity across widespread brain networks. Here we describe a new mechanism for large-scale coordination in the human brain: traveling waves of theta and alpha oscillations. Examining direct brain recordings from neurosurgical patients performing a memory task, we found that contiguous clusters of cortex in individual patients showed oscillations at specific frequencies in the range of 2 to 15 Hz. These clusters displayed spatial phase gradients, indicating that individual oscillation cycles moved across the cortex at ~0.25-0.75 m/s. We found that traveling waves were relevant behaviorally because their propagation correlated with task events and was more consistent during good performance. Traveling waves showed a correlation between propagation speed and temporal frequency, which suggests that they propagate across the cortex following principles of phase-coupled oscillatory networks. By demonstrating that theta and alpha traveling waves are widespread and behaviorally relevant, our results suggest a broad role for brain oscillations in supporting cortical connectivity by organizing neural activity across space and time.

neuroscience↗

bioRxiv2017

The medial temporal lobe organizes memory across time and space: Causal evidence from brain stimulation

The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects abilities to remember items using view-independent (allocentric) navigation strategies. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred.\n\nSignificance StatementNumerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory.

neuroscience↗

bioRxiv2017

Phase-tuned neuronal firing encodes human contextual representations for navigational goals

We previously demonstrated that the phase of oscillations modulates neural activity representing categorical information using human intracranial recordings and high-frequency activity from local field potentials (Watrous et al., 2015b). We extend these findings here using human single-neuron recordings during a navigation task. We identify neurons in the medial temporal lobe with firing-rate modulations for specific navigational goals, as well as for navigational planning and goal arrival. Going beyond this work, using a novel oscillation detection algorithm, we identify phase-locked neural firing that encodes information about a persons prospective navigational goal in the absence of firing rate changes. These results provide evidence for navigational planning and contextual accounts of human MTL function at the single-neuron level. More generally, our findings identify phase-coded neuronal firing as a component of the human neural code.

neuroscience↗

bioRxiv2017

Serial representation of items during working memory maintenance at letter-selective cortical sites

We used intracranial recordings to study brain oscillations during a working memory task. To analyze sites involved in working memory, we focused on sites at which the elevation of the broadband gamma signal depended on which letter was presented. We tested a previously proposed model according to which different items are active at different phases of the theta cycle (in different gamma cycles within the theta cycle). Consistent with this model, the theta phase of letter-induced gamma elevation during maintenance reflected the order of letter presentation. These results suggest that working memory is organized by a theta-gamma code and provide strong support for the serial representation of items held in working memory.

neuroscience↗