Visual perspective as a two-dimensional construct in episodic future thought.

Visual perspective (first-person vs. third-person) is a salient characteristic of memory and mental imagery with important cognitive and behavioural consequences. Most work on visual perspective treats it as a unidimensional construct. However, third-person perspective can have opposite effects on emotion and motivation, sometimes intensifying these and other times acting as a distancing mechanism, as in PTSD. For this reason among others, we propose that visual perspective in memory and mental imagery is best understood as varying along two dimensions: first, the degree to which first-person perspective predominates in the episodic imagery, and second, the degree to which the self is visually salient from a third-person perspective. We show that, in episodic future thinking, these are anticorrelated but non-redundant. These results further our basic understanding of the potent but divergent effects visual perspective has on emotion and motivation, both in everyday life and in psychiatric conditions.

Progressive Thresholding: Shaping and Specificity in Automated Neurofeedback Training.

Neurofeedback has long been proposed as a promising form of adjunctive non-pharmaceutical treatment for a variety of neuropsychological disorders. However, there is much debate over its efficacy and specificity. Many suggest that specificity can only be achieved when a specially trained clinician manually updates reward thresholds that indicate to the trainee when they are modulating their brain activity correctly, during training. We present a novel fully automated reward thresholding algorithm called progressive thresholding and test it with a frontal alpha asymmetry neurofeedback protocol. Progressive thresholding uses dynamic difficulty tuning and individual-specific progress models to simulate the shaping a clinician might perform when setting reward thresholds manually. We demonstrate in a double-blind comparison that progressive thresholding leads to significantly better learning outcomes compared with current automatic reward thresholding algorithms.

Early Intervention with a Multi-Ingredient Dietary Supplement Improves Mood and Spatial Memory in a Triple Transgenic Mouse Model of Alzheimer's Disease.

The increasing global burden of Alzheimer's disease (AD) and failure of conventional treatments to stop neurodegeneration necessitates an alternative approach. Evidence of inflammation, mitochondrial dysfunction, and oxidative stress prior to the accumulation of amyloid-ß in the prodromal stage of AD (mild cognitive impairment; MCI) suggests that early interventions which counteract these features, such as dietary supplements, may ameliorate the onset of MCI-like behavioral symptoms. We administered a polyphenol-containing multiple ingredient dietary supplement (MDS), or vehicle, to both sexes of triple transgenic (3xTg-AD) mice and wildtype mice for 2 months from 2-4 months of age. We hypothesized that the MDS would preserve spatial learning, which is known to be impaired in untreated 3xTg-AD mice by 4 months of age. Behavioral phenotyping of animals was done at 1-2 and 3-4 months of age using a comprehensive battery of tests. As previously reported in males, both sexes of 3xTg-AD mice exhibited increased anxiety-like behavior at 1-2 months of age, prior to deficits in learning and memory, which did not appear until 3-4 months of age. The MDS did not reduce this anxiety or prevent impairments in novel object recognition (both sexes) or on the water maze probe trial (females only). Strikingly, the MDS specifically prevented 3xTg-AD mice (both sexes) from developing impairments (exhibited by untreated 3xTg-AD controls) in working memory and spatial learning. The MDS also increased sucrose preference, an indicator of hedonic tone. These data show that the MDS can prevent some, but not all, psychopathology in an AD model.

Toward an Open-Ended BCI: A User-Centered Coadaptive Design.

Brain-computer interfaces (BCIs) allow users to control a device by interpreting their brain activity. For simplicity, these devices are designed to be operated by purposefully modulating specific predetermined neurophysiological signals, such as the sensorimotor rhythm. However, the ability to modulate a given neurophysiological signal is highly variable across individuals, contributing to the inconsistent performance of BCIs for different users. These differences suggest that individuals who experience poor BCI performance with one class of brain signals might have good results with another. In order to take advantage of individual abilities as they relate to BCI control, we need to move beyond the current approaches. In this letter, we explore a new BCI design aimed at a more individualized and user-focused experience, which we call open-ended BCI. Individual users were given the freedom to discover their own mental strategies as opposed to being trained to modulate a given brain signal. They then underwent multiple coadaptive training sessions with the BCI. Our first open-ended BCI performed similarly to comparable BCIs while accommodating a wider variety of mental strategies without a priori knowledge of the specific brain signals any individual might use. Post hoc analysis revealed individual differences in terms of which sensory modality yielded optimal performance. We found a large and significant effect of individual differences in background training and expertise, such as in musical training, on BCI performance. Future research should be focused on finding more generalized solutions to user training and brain state decoding methods to fully utilize the abilities of different individuals in an open-ended BCI. Accounting for each individual's areas of expertise could have important implications on BCI training and BCI application design.

Examining the role of the temporo-parietal network in memory, imagery, and viewpoint transformations.

The traditional view of the medial temporal lobe (MTL) focuses on its role in episodic memory. However, some of the underlying functions of the MTL can be ascertained from its wider role in supporting spatial cognition in concert with parietal and prefrontal regions. The MTL is strongly implicated in the formation of enduring allocentric representations (e.g., O'Keefe, 1976; King et al., 2002; Ekstrom et al., 2003). According to our BBB model (Byrne et al., 2007), these representations must interact with head-centered and body-centered representations in posterior parietal cortex via a transformation circuit involving retrosplenial areas. Egocentric sensory representations in parietal areas can then cue the recall of allocentric spatial representations in long-term memory and, conversely, the products of retrieval in MTL can generate mental imagery within a parietal "window." Such imagery is necessarily egocentric and forms part of visuospatial working memory, in which it can be manipulated for the purpose of planning/imagining the future. Recent fMRI evidence (Lambrey et al., 2012; Zhang et al., 2012) supports the BBB model. To further test the model, we had participants learn the locations of objects in a virtual scene and tested their spatial memory under conditions that impose varying demands on the transformation circuit. We analyzed how brain activity correlated with accuracy in judging the direction of an object (1) from visuospatial working memory (we assume transient working memory due to the order of tasks and the absence of change in viewpoint, but long-term memory retrieval is also possible), (2) after a rotation of viewpoint, or (3) after a rotation and translation of viewpoint (judgment of relative direction). We found performance-related activity in both tasks requiring viewpoint rotation (ROT and JRD, i.e., conditions 2 and 3) in the core medial temporal to medial parietal circuit identified by the BBB model. These results are consistent with the predictions of the BBB model, and shed further light on the neural mechanisms underlying spatial memory, mental imagery and viewpoint transformations.

Can homeostatic plasticity in deafferented primary auditory cortex lead to travelling waves of excitation?

Travelling waves of activity in neural circuits have been proposed as a mechanism underlying a variety of neurological disorders, including epileptic seizures, migraine auras and brain injury. The highly influential Wilson-Cowan cortical model describes the dynamics of a network of excitatory and inhibitory neurons. The Wilson-Cowan equations predict travelling waves of activity in rate-based models that have sufficiently reduced levels of lateral inhibition. Travelling waves of excitation may play a role in functional changes in the auditory cortex after hearing loss. We propose that down-regulation of lateral inhibition may be induced in deafferented cortex via homeostatic plasticity mechanisms. We use the Wilson-Cowan equations to construct a spiking model of the primary auditory cortex that includes a novel, mathematically formalized description of homeostatic plasticity. In our model, the homeostatic mechanisms respond to hearing loss by reducing inhibition and increasing excitation, producing conditions under which travelling waves of excitation can emerge. However, our model predicts that the presence of spontaneous activity prevents the development of long-range travelling waves of excitation. Rather, our simulations show short-duration excitatory waves that cancel each other out. We also describe changes in spontaneous firing, synchrony and tuning after simulated hearing loss. With the exception of shifts in characteristic frequency, changes after hearing loss were qualitatively the same as empirical findings. Finally, we discuss possible applications to tinnitus, the perception of sound without an external stimulus.

Remembering the past and imagining the future: a neural model of spatial memory and imagery.

The authors model the neural mechanisms underlying spatial cognition, integrating neuronal systems and behavioral data, and address the relationships between long-term memory, short-term memory, and imagery, and between egocentric and allocentric and visual and ideothetic representations. Long-term spatial memory is modeled as attractor dynamics within medial-temporal allocentric representations, and short-term memory is modeled as egocentric parietal representations driven by perception, retrieval, and imagery and modulated by directed attention. Both encoding and retrieval/imagery require translation between egocentric and allocentric representations, which are mediated by posterior parietal and retrosplenial areas and the use of head direction representations in Papez's circuit. Thus, the hippocampus effectively indexes information by real or imagined location, whereas Papez's circuit translates to imagery or from perception according to the direction of view. Modulation of this translation by motor efference allows spatial updating of representations, whereas prefrontal simulated motor efference allows mental exploration. The alternating temporal-parietal flows of information are organized by the theta rhythm. Simulations demonstrate the retrieval and updating of familiar spatial scenes, hemispatial neglect in memory, and the effects on hippocampal place cell firing of lesioned head direction representations and of conflicting visual and ideothetic inputs.

A spiking neuron model of cortical correlates of sensorineural hearing loss: Spontaneous firing, synchrony, and tinnitus.

Hearing loss due to peripheral damage is associated with cochlear hair cell damage or loss and some retrograde degeneration of auditory nerve fibers. Surviving auditory nerve fibers in the impaired region exhibit elevated and broadened frequency tuning, and the cochleotopic representation of broadband stimuli such as speech is distorted. In impaired cortical regions, increased tuning to frequencies near the edge of the hearing loss coupled with increased spontaneous and synchronous firing is observed. Tinnitus, an auditory percept in the absence of sensory input, may arise under these circumstances as a result of plastic reorganization in the auditory cortex. We present a spiking neuron model of auditory cortex that captures several key features of cortical organization. A key assumption in the model is that in response to reduced afferent excitatory input in the damaged region, a compensatory change in the connection strengths of lateral excitatory and inhibitory connections occurs. These changes allow the model to capture some of the cortical correlates of sensorineural hearing loss, including changes in spontaneous firing and synchrony; these phenomena may explain central tinnitus. This model may also be useful for evaluating procedures designed to segregate synchronous activity underlying tinnitus and for evaluating adaptive hearing devices that compensate for selective hearing loss.