The corpus callosum is composed of several subregions, distinct in cellular and functional organization. This organization scheme may render these subregions differentially vulnerable to the aging process. Callosal integrity may be further compromised by cardiovascular risk factors, which negatively influence white matter health. Here, we test for heterochronicity of aging, hypothesizing an anterior-to-posterior gradient of vulnerability to aging that may be altered by effects of cardiovascular health. In 174 healthy adults across the adult lifespan (mean age=53.56 ± 18.90, range=20-94 years old, 58.62% women), pulse pressure (calculated as participant's systolic minus diastolic blood pressure) was assessed to determine cardiovascular risk. A deterministic tractography approach via diffusion weighted imaging was utilized to extract fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) from each of five callosal subregions, serving as estimates of microstructural health. General lin...

Norepinephrine (NE), a neuromodulator released by locus coeruleus (LC) neurons throughout cortex, influences arousal and learning through extra-synaptic vesicle exocytosis. While NE within cortical regions has been viewed as a homogenous field, recent studies have demonstrated heterogeneous axonal dynamics and advances in GPCR-based fluorescent sensors permit direct observation of the local dynamics of NE at cellular scale. To investigate how the spatiotemporal dynamics of NE release in the prefrontal cortex (PFC) affect neuronal firing, we employed in vivo two-photon imaging of layer 2/3 of PFC in order to observe fine-scale neuronal calcium and NE dynamics concurrently. In this proof of principle study, we found that local and global NE fields can decouple from one another, providing a substrate for local NE spatiotemporal activity patterns. Optic flow analysis revealed putative release and reuptake events which can occur at the same location, albeit at different times, indicating the potential to create...

Mismatch negativity (MMN) is commonly recognized as a neural signal of prediction error evoked by deviants from the expected patterns of sensory input. Studies show that MMN diminishes when sequence patterns become more predictable over a longer timescale. This implies that MMN is comprised of multiple subcomponents, each responding to different levels of temporal regularities. To probe the hypothesized subcomponents in MMN, we record human electroencephalography during an auditory local-global oddball paradigm where the tone-to-tone transition probability (local regularity) and the overall sequence probability (global regularity) are manipulated to control temporal predictabilities at two hierarchical levels. We find that the size of MMN is correlated with both probabilities and the spatiotemporal structure of MMN can be decomposed into two distinct subcomponents. Both subcomponents appear as negative waveforms, with one peaking early in the central-frontal area and the other late in a more frontal area. ...

Historically, the orbitofrontal cortex (OFC) has been implicated in a variety of behaviors ranging from reversal learning and inhibitory control to more complex representations of reward value and task space. While modern interpretations of the OFC's function have focused on a role in outcome evaluation, these cognitive processes often require an organism to inhibit a maladaptive response or strategy. Single unit recordings from the OFC in rats performing a stop-change task show that the OFC responds strongly to STOP trials. To investigate the role that the OFC plays in stop-change performance we expressed halorhodopsin (eNpHR3.0) in excitatory neurons in the OFC and tested rats on the stop-change task. Previous work suggests that the OFC differentiates between STOP trials based on trial sequence (i.e., gS trials: STOP trials preceded by a GO versus sS trials: STOP trials preceded by a STOP). We found that yellow light activation of the eNpHR3.0 expressing neurons significantly decreased accuracy only on S...

PVD neuron of Caenorhabditis elegans is a highly polarized cell with well-defined axonal, and dendritic compartments. PVD neuron operates in multiple sensory modalities including the control of both nociceptive touch sensation and body posture. Although both the axon and dendrites of this neuron show a regeneration response following laser-assisted injury, it is rather unclear how the behavior associated with this neuron is affected by the loss of these structures. It is also unclear whether neurite regrowth would lead to functional restoration in these neurons. Upon axotomy, using a femtosecond laser, we saw that harsh touch response was specifically affected leaving the body posture unperturbed. Subsequently, recovery in the touch response is highly correlated to the axon regrowth, which was dependent on DLK-1/MLK-1 MAP Kinase. Dendrotomy of both major and minor primary dendrites affected the wavelength and amplitude of sinusoidal movement without any apparent effect on harsh touch response. We further c...

More and more patients worldwide are diagnosed with dementia, which emphasizes the urgent need for early detection markers. In this study, we built on the auditory hypersensitivity theory of a previous study—which postulated that responses to auditory input in the subcortex as well as cortex are enhanced in cognitive decline—and examined auditory encoding of natural continuous speech at both neural levels for its indicative potential for cognitive decline. We recruited study participants aged 60 years and older, who were divided into two groups based on the Montreal Cognitive Assessment, one group with low scores ( n  = 19, participants with signs of cognitive decline) and a control group ( n  = 25). Participants completed an audiometric assessment and then we recorded their electroencephalography while they listened to an audiobook and click sounds. We derived temporal response functions and evoked potentials from the data and examined response amplitudes for their potential to predict cognitive decline, ...

Cholinergic neurons of the basal forebrain represent the main source of cholinergic innervation of large parts of the neocortex and are involved in adults in the modulation of attention, memory, and arousal. During the first postnatal days, they play a crucial role in the development of cortical neurons and cortical cytoarchitecture. However, their characteristics, during this period have not been studied. To understand how they can fulfill this role, we investigated the morphological and electrophysiological maturation of cholinergic neurons of the substantia innominata–nucleus basalis of Meynert (SI/NBM) complex in the perinatal period in mice. We show that cholinergic neurons, whether or not they express gamma-aminobutyric acid (GABA) as a cotransmitter, are already functional at Embryonic Day 18. Until the end of the first postnatal week, they constitute a single population of neurons with a well developed dendritic tree, a spontaneous activity including bursting periods, and a short-latency response t...

Infrared neural stimulation (INS) is a promising area of interest for the clinical application of a neuromodulation method. This is in part because of its low invasiveness, whereby INS modulates the activity of the neural tissue mainly through temperature changes. Additionally, INS may provide localized brain stimulation with less tissue damage. The inferior colliculus (IC) is a crucial auditory relay nucleus and a potential target for clinical application of INS to treat auditory diseases and develop artificial hearing devices. Here, using continuous INS with low to high-power density, we demonstrate the laminar modulation of neural activity in the mouse IC in the presence and absence of sound. We investigated stimulation parameters of INS to effectively modulate the neural activity in a facilitatory or inhibitory manner. A mathematical model of INS-driven brain tissue was first simulated, temperature distributions were numerically estimated, and stimulus parameters were selected from the simulation resul...

Elicited upon violation of regularity in stimulus presentation, mismatch negativity (MMN) reflects the brain's ability to perform automatic comparisons between consecutive stimuli and provides an electrophysiological index of sensory error detection whereas P300 is associated with cognitive processes such as updating of the working memory. To date, there has been extensive research on the roles of MMN and P300 individually, because of their potential to be used as clinical markers of consciousness and attention, respectively. Here, we intend to explore with an unsupervised and rigorous source estimation approach, the underlying cortical generators of MMN and P300, in the context of prediction error propagation along the hierarchies of brain information processing in healthy human participants. The existing methods of characterizing the two ERPs involve only approximate estimations of their amplitudes and latencies based on specific sensors of interest. Our objective is twofold: first, we introduce a novel ...

The ability to remember changes in the surroundings is fundamental for daily life. It has been proposed that novel events producing dopamine release in the hippocampal CA1 region could modulate spatial memory formation. However, the role of hippocampal dopamine increase on weak or strong spatial memories remains unclear. We show that male mice exploring two objects located in a familiar environment for 5 min created a short-term memory (weak) that cannot be retrieved 1 d later, whereas 10 min exploration created a long-term memory (strong) that can be retrieved 1 d later. Remarkably, hippocampal dopamine elevation during the encoding of weak object location memories (OLMs) allowed their retrieval 1 d later but dopamine elevation during the encoding of strong OLMs promoted the preference for a familiar object location over a novel object location after 24 h. Moreover, dopamine uncaging after the encoding of OLMs did not have effect on weak memories whereas on strong memories diminished the exploration of th...