Affective Visual Circuit Dysfunction in Trauma and Stress-Related Disorders.

Posttraumatic stress disorder (PTSD) is widely recognized as involving disruption of core neurocircuitry that underlies processing, regulation, and response to threat. In particular, the prefrontal cortex-hippocampal-amygdala circuit is a major contributor to posttraumatic dysfunction. However, the functioning of core threat neurocircuitry is partially dependent on sensorial inputs, and previous research has demonstrated that dense, reciprocal connections exist between threat circuits and the ventral visual stream. Furthermore, emergent evidence suggests that trauma exposure and resultant PTSD symptoms are associated with altered structure and function of the ventral visual stream. In the current review, we discuss evidence that both threat and visual circuitry together are an integral part of PTSD pathogenesis. An overview of the relevance of visual processing to PTSD is discussed in the context of both basic and translational research, highlighting the impact of stress on affective visual circuitry. This review further synthesizes emergent literature to suggest potential timing-dependent effects of traumatic stress on threat and visual circuits that may contribute to PTSD development. We conclude with recommendations for future research to move the field toward a more complete understanding of PTSD neurobiology.

Impact of deprivation and preferential usage on functional connectivity between early visual cortex and category selective visual regions.

Human behavior can be remarkably shaped by experience, such as the removal of sensory input. Many studies of conditions such as stroke, limb amputation, and vision loss have examined how the removal of input changes brain function. However, an important question has yet to be answered: when input is lost, does the brain change its connectivity to preferentially use some remaining inputs over others? In individuals with healthy vision, the central portion of the retina is preferentially used for everyday visual tasks, due to its ability to discriminate fine details. However, when central vision is lost in conditions like macular degeneration, peripheral vision must be relied upon for those everyday tasks, with certain portions receiving "preferential" usage over others. Using resting-state fMRI collected during total darkness, we examined how deprivation and preferential usage influence the intrinsic functional connectivity of sensory cortex by studying individuals with selective vision loss due to late stages of macular degeneration. We found that cortical regions representing spared portions of the peripheral retina, regardless of whether they are preferentially used, exhibit plasticity of intrinsic functional connectivity in macular degeneration. Cortical representations of spared peripheral retinal locations showed stronger connectivity to MT, a region involved in processing motion. These results suggest that long-term loss of central vision can produce widespread effects throughout spared representations in early visual cortex, regardless of whether those representations are preferentially used. These findings support the idea that connections to visual cortex maintain the capacity for change well after critical periods of visual development. Highlights: Portions of early visual cortex representing central vs. peripheral vision exhibit different patterns of connectivity to category-selective visual regions.When central vision is lost, cortical representations of peripheral vision display stronger functional connections to MT than central representations.When central vision is lost, connectivity to regions selective for tasks that involve central vision (FFA and PHA) are not significantly altered.These effects do not depend on which locations of peripheral vision are used more.

Sensory alterations in post-traumatic stress disorder.

PTSD is characterized by difficulties in accurately evaluating the threat value of sensory stimuli. While the role of canonical fear and threat neural circuitry in this ability has been well studied, recent lines of evidence suggest a need to include more emphasis on sensory processing in the conceptualization of PTSD symptomology. Specifically, studies have demonstrated a strong association between variability in sensory processing regions and the severity of PTSD symptoms. In this review, we summarize recent findings that underscore the importance of sensory processing in PTSD, in addition to the structural and functional characteristics of associated sensory brain regions. First, we discuss the link between PTSD and various behavioral aspects of sensory processing. This is followed by a discussion of recent findings that link PTSD to variability in the structure of both gray and white matter in sensory brain regions. We then delve into how brain activity (measured with task-based and resting-state functional imaging) in sensory regions informs our understanding of PTSD symptomology.

Cortical plasticity in central vision loss: Cortical thickness and neurite structure.

Late-stage macular degeneration (MD) often causes retinal lesions depriving an individual of central vision, forcing them to learn to use peripheral vision for daily tasks. To compensate, many patients develop a preferred retinal locus (PRL), an area of peripheral vision used more often than equivalent regions of spared vision. Thus, associated portions of cortex experience increased use, while portions of cortex associated with the lesion are deprived of sensory input. Prior research has not well examined the degree to which structural plasticity depends on the amount of use across the visual field. Cortical thickness, neurite density, and orientation dispersion were measured at portions of cortex associated with the PRL, the retinal lesion, and a control region in participants with MD as well as age-matched, gender-matched, and education-matched controls. MD participants had significantly thinner cortex in both the cortical representation of the PRL (cPRL) and the control region, compared with controls, but no significant differences in thickness, neurite density, or orientation dispersion were found between the cPRL and the control region as functions of disease or onset. This decrease in thickness is driven by a subset of early-onset participants whose patterns of thickness, neurite density, and neurite orientation dispersion are distinct from matched control participants. These results suggest that people who develop MD earlier in adulthood may undergo more structural plasticity than those who develop it late in life.

Background connectivity between frontal and sensory cortex depends on task state, independent of stimulus modality.

The human brain has the ability to process identical information differently depending on the task. In order to perform a given task, the brain must select and react to the appropriate stimuli while ignoring other irrelevant stimuli. The dynamic nature of environmental stimuli and behavioral intentions requires an equally dynamic set of responses within the brain. Collectively, these responses act to set up and maintain states needed to perform a given task. However, the mechanisms that allow for setting up and maintaining a task state are not fully understood. Prior evidence suggests that one possible mechanism for maintaining a task state may be through altering 'background connectivity,' connectivity that exists independently of the trials of a task. Although previous studies have suggested that background connectivity contributes to a task state, these studies have typically not controlled for stimulus characteristics, or have focused primarily on relationships among areas involved with visual sensory processing. In the present study we examined background connectivity during tasks involving both visual and auditory stimuli. We examined the connectivity profiles of both visual and auditory sensory cortex that allow for selection of task-relevant stimuli, demonstrating the existence of a potentially universal pattern of background connectivity underlying attention to a stimulus. Participants were presented with simultaneous auditory and visual stimuli and were instructed to respond to only one, while ignoring the other. Using functional MRI, we observed task-based modulation of the background connectivity profile for both the auditory and visual cortex to certain brain regions. There was an increase in background connectivity between the task-relevant sensory cortex and control areas in the frontal cortex. This increase in synchrony when receiving the task-relevant stimulus as compared to the task irrelevant stimulus may be maintaining paths for passing information within the cortex. These task-based modulations of connectivity occur independently of stimuli and could be one way the brain sets up and maintains a task state.

VAChT overexpression increases acetylcholine at the synaptic cleft and accelerates aging of neuromuscular junctions.

BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS). METHODS: Chat-ChR2-EYFP (VAChTHyp) mice containing multiple copies of the vesicular acetylcholine transporter (VAChT), mutant superoxide dismutase 1 (SOD1G93A), and Chat-IRES-Cre and tdTomato transgenic mice were used in this study. NMJs, muscle fibers, and α-motor neurons' somata and their axons were examined using a light microscope. Transcripts for select genes in muscles and spinal cords were assessed using real-time quantitative PCR. Motor function tests were carried out using an inverted wire mesh and a rotarod. Electrophysiological recordings were collected to examine miniature endplate potentials (MEPP) in muscles. RESULTS: We show that VAChT is elevated in the spinal cord and at NMJs of VAChTHyp mice. We also show that the amplitude of MEPPs is significantly higher in VAChTHyp muscles, indicating that more ACh is loaded into synaptic vesicles and released into the synaptic cleft at NMJs of VAChTHyp mice compared to control mice. While the development of NMJs was not affected in VAChTHyp mice, NMJs prematurely acquired age-related structural alterations in adult VAChTHyp mice. These structural changes at NMJs were accompanied by motor deficits in VAChTHyp mice. However, cellular features of muscle fibers and levels of molecules with critical functions at the NMJ and in muscle fibers were largely unchanged in VAChTHyp mice. In the SOD1G93A mouse model for ALS, increasing synaptic ACh accelerated degeneration of NMJs caused motor deficits and resulted in premature death specifically in male mice. CONCLUSIONS: The data presented in this manuscript demonstrate that increasing levels of ACh at the synaptic cleft promote degeneration of adult NMJs, contributing to age- and disease-related motor deficits. We thus propose that maintaining normal cholinergic signaling in muscles will slow degeneration of NMJs and attenuate loss of motor function caused by aging and neuromuscular diseases.