Neuroscience and Neurobiology Commons^™

Differential Joint-Specific Corticospinal Tract Projections Within The Cervical Enlargement, Curtis O. Asante, John H. Martin

Publications and Research

The motor cortex represents muscle and joint control and projects to spinal cord interneurons and–in many primates, including humans–motoneurons, via the corticospinal tract (CST). To examine these spinal CST anatomical mechanisms, we determined if motor cortex sites controlling individual forelimb joints project differentially to distinct cervical spinal cord territories, defined regionally and by the locations of putative last-order interneurons that were transneuronally labeled by intramuscular injection of pseudorabies virus. Motor cortex joint-specific sites were identified using intracorticalmicrostimulation. CST segmental termination fields from joint-specific sites, determined using anterograde tracers, comprised a high density core of terminations that was consistent between animals …

Cholinergic Enhancement Of Brain Activation In Mild Cognitive Impairment During Episodic Memory Encoding, Shannon L. Risacher, Yang Wang, Heather A. Wishart, Laura A. Rabin, Laura A. Flashman, Brenna C. Mcdonald, John D. West, Robert B. Santulli, Andrew J. Saykin

Publications and Research

Objective: To determine the physiological impact of treatment with donepezil (Aricept) on neural circuitry supporting episodic memory encoding in patients with amnestic mild cognitive impairment (MCI) using functional magnetic resonance imaging (fMRI).

Methods: Eighteen patients with MCI and 20 age-matched healthy controls (HC) were scanned twice while performing an event-related verbal episodic encoding task. MCI participants were scanned before treatment and after approximately 3 months on donepezil; HCwere untreated but rescanned at the same interval.Voxel-level analyses assessed treatment effects on activation profiles in MCI patients relative to retest changes in non-treated HC. Changes in task-related connectivity in medial temporal circuitry …

Unconscious Priming Requires Early Visual Cortex At Specific Temporal Phases Of Processing, Marjan Persuh, Tony Ro

Publications and Research

Although examples of unconscious shape priming have been well documented, whether such priming requires early visual cortex (V1/V2) has not been established. In the current study, we used TMS of V1/V2 at varying temporal intervals to suppress the visibility of preceding shape primes while the interval between primes and targets was kept constant. Our results show that, although conscious perception requires V1/V2, unconscious priming can occur without V1/V2 at an intermediate temporal interval but not at early (5–25 msec) or later (65–125 msec) stages of processing. Because the later time window of unconscious priming suppression has been proposed to interfere …

Explorations Of Object And Location Memory Using Fmri, Andrew D. Passaro, L. Caitlin Elmore, Timothy M. Ellmore, Kenneth J. Leising, Andrew C. Papanicolaou, Anthony A. Wright

Publications and Research

Content-specific sub-systems of visual working memory (VWM) have been explored in many neuroimaging studies with inconsistent findings and procedures across experiments. The present study employed functional magnetic resonance imaging (fMRI) and a change detection task using a high number of trials and matched stimulus displays across object and location change (what vs. where) conditions. Furthermore, individual task periods were studied independently across conditions to identify differences corresponding to each task period. Importantly, this combination of task controls has not previously been described in the fMRI literature. Composite results revealed differential frontoparietal activation during each task period. A separation of object …

Effortless Awareness: Using Real Time Neurofeedback To Investigate Correlates Of Posterior Cingulate Cortex Activity In Meditators' Self-Report, Kathleen A. Garrison, Juan F. Santoyo, Jake H. Davis, Thomas A. Thomhill Iv, Catherine E. Kerr, Judson A. Brewer

Publications and Research

Neurophenomenological studies seek to utilize first-person self-report to elucidate cognitive processes related to physiological data. Grounded theory offers an approach to the qualitative analysis of self-report, whereby theoretical constructs are derived from empirical data. Here we used grounded theory methodology (GTM) to assess how the first-person experience of meditation relates to neural activity in a core region of the default mode network—the posterior cingulate cortex (PCC). We analyzed first-person data consisting of meditators' accounts of their subjective experience during runs of a real time fMRI neurofeedback study of meditation, and third-person data consisting of corresponding feedback graphs of PCC activity …

Neural Activations During Visual Sequence Learning Leave A Trace In Post-Training Spontaneous Eeg, Clara Moisello, Hadj Boumediene Meziane, Simon Kelly, Bernardo Perfetti, Svetlana Kvint, Nicholas Voutsinas, Daniella Blanco, Angelo Quartarone, Giulio Tononi, Maria Felice Ghilardi

Publications and Research

Recent EEG studies have shown that implicit learning involving specific cortical circuits results in an enduring local trace manifested as local changes in spectral power. Here we used a well characterized visual sequence learning task and high density-(hd-)EEG recording to determine whether also declarative learning leaves a post-task, local change in the resting state oscillatory activity in the areas involved in the learning process. Thus, we recorded hd-EEG in normal subjects before, during and after the acquisition of the order of a fixed spatial target sequence (VSEQ) and during the presentation of targets in random order (VRAN). We first determined …

Dominance Of Orientation Over Frequency In The Perception Of 3-D Slant And Shape, Danny M. Tam, Ji Shin, Andrea Li

Publications and Research

In images of textured three-dimensional surfaces, pattern changes can be characterized as changes in orientation and spatial frequency, features for which neurons in primary visual cortex are classically selective. Previously, we have demonstrated that correct 3-D shape perception is contingent on the visibility of orientation flows that run parallel to the surface curvature. We sought to determine the relative contributions of orientation modulations (OMs) and frequency modulations (FMs) for the detection of slant and shape from 3-D surfaces. Results show that 1) when OM and FM indicate inconsistent degrees of surface slant or curvature, observer responses were consistent with the …

Sex-Specific Brain Deficits In Auditory Processing In An Animal Model Of Cocaine-Related Schizophrenic Disorders, Patricia A. Broderick, Taylor Rosenbaum

Publications and Research

Cocaine is a psychostimulant in the pharmacological class of drugs called Local Anesthetics. Interestingly, cocaine is the only drug in this class that has a chemical formula comprised of a tropane ring and is, moreover, addictive. The correlation between tropane and addiction is well-studied. Another well-studied correlation is that between psychosis induced by cocaine and that psychosis endogenously present in the schizophrenic patient. Indeed, both of these psychoses exhibit much the same behavioral as well as neurochemical properties across species. Therefore, in order to study the link between schizophrenia and cocaine addiction, we used a behavioral paradigm called Acoustic Startle. …

Neural Processing Of Facial Identity And Emotion In Infants At High-Risk For Autism Spectrum Disorders, Sharon E. Fox, Jennifer B. Wagner, Christine L. Shrock, Helen Tager-Flusberg, Charles A. Nelson

Publications and Research

Deficits in face processing and social impairment are core characteristics of autism spectrum disorder. The present work examined 7-month-old infants at high-risk for developing autism and typically developing controls at low-risk, using a face perception task designed to differentiate between the effects of face identity and facial emotions on neural response using functional Near-Infrared Spectroscopy. In addition, we employed independent component analysis, as well as a novel method of condition-related component selection and classification to identify group differences in hemodynamic wave forms and response distributions associated with face and emotion processing.The results indicate similarities of waveforms, but differences in the …

Unconscious Processing Of Unattended Features In Human Visual Cortex, Tatiana Aloi Emmanouil, Philip Burton, Tony Ro

Publications and Research

Unconscious processing has been convincingly demonstrated for task-relevant feature dimensions. However, it is possible that the visual system is capable of more complex unconscious operations, extracting visual features even when they are unattended and task irrelevant. In the current study, we addressed this question by measuring unconscious priming using a task in which human participants attended to a target object's shape while ignoring its color. We measured both behavioral priming effects and priming-related fMRI activations from primes that were unconsciously presented using metacontrast masking. The results showed faster RTs and decreases in fMRI activation only when the primes were identical …

A Naturally-Occurring Histone Acetyltransferase Inhibitor Derived From Garcinia Indica Impairs Newly Acquired And Reactivated Fear Memories, Stephanie A. Maddox, Casey S. Watts, Valerie Doyere, Glenn E. Schafe

Publications and Research

The study of the cellular and molecular mechanisms underlying the consolidation and reconsolidation of traumatic fear memories has progressed rapidly in recent years, yet few compounds have emerged that are readily useful in a clinical setting for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD). Here, we use a combination of biochemical, behavioral, and neurophysiological methods to systematically investigate the ability of garcinol, a naturallyoccurring histone acetyltransferase (HAT) inhibitor derived from the rind of the fruit of the Kokum tree (Garcina indica), to disrupt the consolidation and reconsolidation of Pavlovian fear conditioning, a widely studied rodent model …

Peripheral Nerve Injury Is Associated With Chronic, Reversible Changes In Global Dna Methylation In The Mouse Prefrontal Cortex, Maral Tajerian, Sebastian Alvarado, Magali Millecamps, Pascal Vachon, Cecilia Crosby, M. Catherine Bushnell, Moshe Szyf, Laura S. Stone

Publications and Research

Changes in brain structure and cortical function are associated with many chronic pain conditions including low back pain and fibromyalgia. The magnitude of these changes correlates with the duration and/or the intensity of chronic pain. Most studies report changes in common areas involved in pain modulation, including the prefrontal cortex (PFC), and pain-related pathological changes in the PFC can be reversed with effective treatment. While the mechanisms underlying these changes are unknown, they must be dynamically regulated. Epigenetic modulation of gene expression in response to experience and environment is reversible and dynamic. Epigenetic modulation by DNA methylation is associated with …

Computational Model Of Neuron-Astrocyte Interputational Model Of Neuron-Astrocyte Interactions During Focal Seizure Generationactions During Focal Seizure Generation, Davide Reato, Mario Cammarota, Lucas C. Parra, Giorgio Carmignoto

Publications and Research

Empirical research in the last decade revealed that astrocytes can respond to neurotransmitters with Ca2+ elevations and generate feedback signals to neurons which modulate synaptic transmission and neuronal excitability. This discovery changed our basic understanding of brain function and provided new perspectives for how astrocytes can participate not only to information processing, but also to the genesis of brain disorders, such as epilepsy. Epilepsy is a neurological disorder characterized by recurrent seizures that can arise focally at restricted areas and propagate throughout the brain. Studies in brain slice models suggest that astrocytes contribute to epileptiform activity by increasing neuronal excitability …

Coordination Between Proteasome Impairment And Caspase Activation Leading To Tau Pathology: Neuroprotection By Camp, M. J. Metcalfe, Q. Huang, Maria E. Figueiredo-Pereira

Publications and Research

Neurofibrillary tangles (NFTs) are hallmarks of Alzheimer’s disease (AD). The main component of NFTs is TAU, a highly soluble microtubule-associated protein. However, when TAU is cleaved at Asp421 by caspases it becomes prone to aggregation leading to NFTs. What triggers caspase activation resulting in TAU cleavage remains unclear. We investigated in rat cortical neurons a potential coordination between proteasome impairment and caspase activation. We demonstrate that upon proteasome inhibition, the early accumulation of detergent-soluble ubiquitinated (SUb) proteins paves the way to caspase activation and TAU pathology. This occurs with two drugs that inhibit the proteasome by different means: the product …

Dynamic Gene Expression In The Human Cerebral Cortex Distinguishes Children From Adults, Kirstin N. Sterner, Amy Weckle, Harry T. Chugani, Adi L. Tarca, Chet C. Sherwood, Patrick R. Hof, Christopher W. Kuzawa, Amy M. Boddy, Asad Abbas, Ryan L. Raaum, Lucie Grégoire, Leonard Lipovich, Lawrence I. Grossman, Monica Uddin, Morris Goodman, Derek E. Wildman

Publications and Research

In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR>0). Moreover, genes known to …

Iconic Memory Requires Attention, Marjan Persuh, Boris Genzer, Robert D. Melara

Publications and Research

Two experiments investigated whether attention plays a role in iconic memory, employing either a change detection paradigm (Experiment 1) or a partial-report paradigm (Experiment 2). In each experiment, attention was taxed during initial display presentation, focusing the manipulation on consolidation of information into iconic memory, prior to transfer into working memory. Observers were able to maintain high levels of performance (accuracy of change detection or categorization) even when concurrently performing an easy visual search task (low load). However, when the concurrent search was made difficult (high load), observers' performance dropped to almost chance levels, while search accuracy held at single-task …

Integration Of Subthreshold And Suprathreshold Excitatory Barrages Along The Somatodendritic Axis Of Pyramidal Neurons, Hysell V. Oviedo, Alex D. Reyes

Publications and Research

Neurons integrate inputs arriving in different cellular compartments to produce action potentials that are transmitted to other neurons. Because of the voltage- and time-dependent conductances in the dendrites and soma, summation of synaptic inputs is complex. To examine summation of membrane potentials and firing rates, we performed whole-cell recordings from layer 5 cortical pyramidal neurons in acute slices of the rat’s somatosensory cortex. We delivered subthreshold and suprathreshold stimuli at the soma and several sites on the apical dendrite, and injected inputs that mimic synaptic barrages at individual or distributed sites. We found that summation of subthreshold potentials differed from …

Pten Regulation Of Local And Long-Range Connections In Mouse Auditory Cortex, Qiaojie Xiong, Hysell V. Oviedo, Lloyd C. Trotman, Anthony M. Zador

Publications and Research

Autism spectrum disorders (ASDs) are highly heritable developmental disorders caused by a heterogeneous collection of genetic lesions. Here we use a mouse model to study the effect on cortical connectivity of disrupting the ASD candidate gene PTEN (phosphatase and tensin homolog deleted on chromosome 10). Through Cre-mediated recombination, we conditionally knocked out PTEN expression in a subset of auditory cortical neurons. Analysis of long-range connectivity using channelrhodopsin-2 revealed that the strength of synaptic inputs from both the contralateral auditory cortex and from the thalamus onto PTEN-cko neurons was enhanced compared with nearby neurons with normal PTEN expression. Laser-scanning photostimulation showed …

Serotonin 1a Receptor-Mediated Signaling Through Erk And Pkcα Is Essential For Normal Synaptogenesis In Neonatal Mouse Hippocampus, A. Mogha, Sara R. Guariglia, Priya Ranjan Debata, Guang Y. Wen, Probal Banerjee

Publications and Research

Aberrant expression of the presynaptic serotonin 1A receptor (5-HT_1A-R) because of a polymorphism in the 5-HT_1A-R gene is associated with severe depression in human, whereas its absence up to postnatal day 21 (P21) in the forebrain of mice results in heightened anxiety in adulthood. These observations collectively indicate that the 5-HT1A-R has a crucial role in brain development. To understand the mechanistic underpinnings of this phenomenon, we used organotypic slice cultures of hippocampi from C57BL6 mice (C57) at P15, which coincides with the peak of neonatal synaptogenesis. Stimulation of the hippocampal 5-HT1A-R caused a dramatic increase …

Temporal Sensitivity Changes With Extended Training In A Bisection Task In A Transgenic Rat Model, Bruce L. Brown, Sophie Hohn, Alexis Faure, Stephan Von Horsten, Pascale Le Blanc, Nathalie Desvignes, Nicole El Massioui, Valerie Doyere

Publications and Research

The present study investigated temporal perception in a Huntington disease transgenic rat model using a temporal bisection procedure. After initial discrimination training in which animals learned to press one lever after a 2-s tone duration, and the other lever after a 8-s tone duration for food reward, the bisection procedure was implemented in which intermediate durations with no available reinforcement were interspersed with trials with the anchor durations. Bisection tests were repeated in a longitudinal design from 4 to 8 months of age.The results showed that response latencies evolved from a monotonic step-function to an inverted U-shaped function with repeated …

Prenatal Cocaine Exposure Increases Synaptic Localization Of A Neuronal Rasgef, Grasp-1 Via Hyperphosphorylation Of Ampar Anchoring Protein, Grip, Kalindi Bakshi, Mary Kosciuk, Robert G. Nagele, Eitan Friedman, Hoau-Yan Wang

Publications and Research

Prenatal cocaine exposure causes sustained phosphorylation of the synaptic anchoring protein, glutamate receptor interacting protein (GRIP1/2), preventing synaptic targeting of the GluR2/3-containing alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid-type glutamate receptors (AMPARs; J. Neurosci. 29: 6308–6319, 2009). Because overexpression of GRIP-associated neuronal rasGEF protein (GRASP-1) specifically reduces the synaptic targeting of AMPARs, we hypothesized that prenatal cocaine exposure enhances GRASP-1 synaptic membrane localization leading to hyper-activation of ras family proteins and heightened actin polymerization. Our results show a markedly increased GRIP1-associated GRASP-1 content with approximately 40% reduction in its rasGEF activity in frontal cortices (FCX) of 21-day-old (P21) prenatal cocaineexposed rats. This cocaine effect …

Insightful Problem Solving In An Asian Elephant, Preston Foerder, Marie Galloway, Tony Barthel, Donald E. Moore Iii, Diana Reiss

Publications and Research

The ‘‘aha’’ moment or the sudden arrival of the solution to a problem is a common human experience. Spontaneous problem solving without evident trial and error behavior in humans and other animals has been referred to as insight. Surprisingly, elephants, thought to be highly intelligent, have failed to exhibit insightful problem solving in previous cognitive studies. We tested whether three Asian elephants (Elephas maximus) would use sticks or other objects to obtain food items placed out-of-reach and overhead. Without prior trial and error behavior, a 7-year-old male Asian elephant showed spontaneous problem solving by moving a large plastic cube, on …

Bone Morphogenetic Protein Inhibition Promotes Neurological Recovery After Intraventricular Hemorrhage, Krishna Dummula, Govindaiah Vinukonda, Philip Chu, Yiping Xing, Furong Hu, Sabrina Mailk, Anna Csiszar, Caroline Chua, Peter Mouton, Robert J. Kayton, Joshua C. Brumberg, Rashmi Bansal, Praveen Ballabh

Publications and Research

Intraventricular hemorrhage (IVH) results in neural cell death and white matter injury in premature infants. No therapeutic strategy is currently available against this disorder. Bone morphogenetic protein (BMP) signaling suppresses oligodendrocyte development through basic-helix-loop-helix (bHLH) transcription factors and promotes astrocytosis. Therefore, we hypothesized that IVH in premature newborns initiates degeneration and maturation arrest of oligodendrocyte lineage and that BMP inhibition alleviates hypomyelination, gliosis, and motor impairment in the survivors of IVH. To test the hypotheses, a rabbit model of IVH was used in which premature rabbit pups (E29) are treated with intraperitoneal glycerol at 2 hours of age to induce …

“What” And “Where” In Auditory Sensory Processing: A High-Density Electrical Mapping Study Of Distinct Neural Processes Underlying Sound Object Recognition And Sound Localization, Victoria M. Leavitt, Sophie Molholm, Manuel Gomez-Ramirez, John J. Foxe

Publications and Research

Functionally distinct dorsal and ventral auditory pathways for sound localization (WHERE) and sound object recognition (WHAT) have been described in non-human primates. A handful of studies have explored differential processing within these streams in humans, with highly inconsistent findings. Stimuli employed have included simple tones, noise bursts, and speech sounds, with simulated left–right spatial manipulations, and in some cases participants were not required to actively discriminate the stimuli. Our contention is that these paradigms were not well suited to dissociating processing within the two streams. Our aim here was to determine how early in processing we …

Pulsed Out Of Awareness: Eeg Alpha Oscillations Represent A Pulsed-Inhibition Of Ongoing Cortical Processing, Kyle E. Mathewson, Alejandro Lleras, Diane M. Beck, Monica Fabiani, Tony Ro, Gabriele Gratton

Publications and Research

Alpha oscillations are ubiquitous in the brain, but their role in cortical processing remains a matter of debate. Recently, evidence has begun to accumulate in support of a role for alpha oscillations in attention selection and control. Here we first review evidence that 8–12 Hz oscillations in the brain have a general inhibitory role in cognitive processing, with an emphasis on their role in visual processing. Then, we summarize the evidence in support of our recent proposal that alpha represents a pulsed-inhibition of ongoing neural activity. The phase of the ongoing electroencephalography can influence evoked activity and subsequent processing, and …

Alternation Rate In Perceptual Bistability Is Maximal At And Symmetric Around Equi-Dominance, Rubén Moreno-Bote, Asya Shpiro, John Rinzel, Nava Rubin

Publications and Research

When an ambiguous stimulus is viewed for a prolonged time, perception alternates between the different possible interpretations of the stimulus. The alternations seem haphazard, but closer inspection of their dynamics reveals systematic properties in many bistable phenomena. Parametric manipulations result in gradual changes in the fraction of time a given interpretation dominates perception, often over the entire possible range of zero to one. The mean dominance durations of the competing interpretations can also vary over wide ranges (from less than a second to dozens of seconds or more), but finding systematic relations in how they vary has proven difficult. Following …

Neural Substrates Of Reliability-Weighted Visual-Tactile Multisensory Integration, Michael S. Beauchamp, Siavash Pasalar, Tony Ro

Publications and Research

As sensory systems deteriorate in aging or disease, the brain must relearn the appropriate weights to assign each modality during multisensory integration. Using blood-oxygen level dependent functional magnetic resonance imaging of human subjects, we tested a model for the neural mechanisms of sensory weighting, termed “weighted connections.” This model holds that the connection weights between early and late areas vary depending on the reliability of the modality, independent of the level of early sensory cortex activity. When subjects detected viewed and felt touches to the hand, a network of brain areas was active, including visual areas in lateral occipital cortex, …

Manipulating Neuronal Circuits With Endogenous And Recombinant Cell-Surface Tethered Modulators, Mande Holford, Sebastian Auer, Martin Laqua, Ines Ibanez-Tallon

Publications and Research

Neuronal circuits depend on the precise regulation of cell-surface receptors and ion channels. An ongoing challenge in neuroscience research is deciphering the functional contribution of specifi c receptors and ion channels using engineered modulators. A novel strategy, termed “tethered toxins”, was recently developed to characterize neuronal circuits using the evolutionary derived selectivity of venom peptide toxins and endogenous peptide ligands, such as lynx1 prototoxins. Herein, the discovery and engineering of cell-surface tethered peptides is reviewed, with particular attention given to their cell-autonomy, modular composition, and genetic targeting in different model organisms. The relative ease with which tethered peptides can be …

To See Or Not To See: Prestimulus Α Phase Predicts Visual Awareness, Kyle E. Mathewson, Gabriele Gratton, Monica Fabiani, Diane M. Beck, Tony Ro

Publications and Research

We often fail to see something that at other times is readily detectable. Because the visual stimulus itself is unchanged, this variability in conscious awareness is likely related to changes in the brain. Here we show that the phase of EEG α rhythm measured over posterior brain regions can reliably predict both subsequent visual detection and stimulus-elicited cortical activation levels in a metacontrast masking paradigm. When a visual target presentation coincides with the trough of an α wave, cortical activation is suppressed as early as 100 ms after stimulus onset, and observers are less likely to detect the target. Thus, …

Neural Substrates Of Sound–Touch Synesthesia After A Thalamic Lesion, Michael S. Beauchamp, Tony Ro

Publications and Research

Neural plasticity induced by stroke can mediate positive outcomes, such as recovery of function, but can also result in the formation of abnormal connections with negative consequences for perception and cognition. In three experiments using blood-oxygen level dependent (BOLD) functional magnetic resonance imaging, we examined the neural substrates of acquired auditory-tactile synesthesia, in which certain sounds can produce an intense somatosensory tingling sensation in a patient with a thalamic lesion. Compared with nine normal controls, the first experiment showed that the patient had a threefold greater BOLD response to sounds in the parietal operculum, the location of secondary somatosensory cortex. …