Papadimitriou C, Ferdoash A, Snyder LH. Ghosts in the machine: memory interference from the previous trial. J Neurophysiol 113: 567-577, 2015. First published November 5, 2014 doi:10.1152/jn.00402.2014.-Previous memoranda can interfere with the memorization or storage of new information, a concept known as proactive interference. Studies of proactive interference typically use categorical memoranda and match-to-sample tasks with categorical measures such as the proportion of correct to incorrect responses. In this study we instead train five macaques in a spatial memory task with continuous memoranda and responses, allowing us to more finely probe working memory circuits. We first ask whether the memoranda from the previous trial result in proactive interference in an oculomotor delayed response task. We then characterize the spatial and temporal profile of this interference and ask whether this profile can be predicted by an attractor network model of working memory. We find that memory in the current trial shows a bias toward the location of the memorandum of the previous trial. The magnitude of this bias increases with the duration of the memory period within which it is measured. Our simulations using standard attractor network models of working memory show that these models easily replicate the spatial profile of the bias. However, unlike the behavioral findings, these attractor models show an increase in bias with the duration of the previous rather than the current memory period. To model a bias that increases with current trial duration we posit two separate memory stores, a rapidly decaying visual store that resists proactive interference effects and a sustained memory store that is susceptible to proactive interference. Payne et al. 1992), and language comprehension (Daneman and Carpenter 1980;Just and Carpenter 1992;Daneman and Merikle 1996), and hence an understanding of the circuitry of working memory is critical for understanding higher cognition. Spatial working memory provides an excellent model system for this purpose. The memoranda, locations in space, are continuous and well defined, as are the responses that provide a read out for these memoranda. Animals can be easily trained to perform spatial working memory tasks, and neural circuits can then be directly interrogated using various electrophysiological techniques. A number of models for working memory have been proposed (Durstewitz et al. 2000;Miyake and Shah 1999;Baddeley 2012). Here we present findings that can constrain these models and illuminate the mechanisms by which memory is degraded.Working memory may be degraded due to interference or distraction from task-irrelevant events that occur before or during the memory period. Prior computational and behavioral studies on memory interference have focused on the spatial working memory system because it provides continuous measures for both stimuli and responses and is well suited to studying partial memory degradation (Compte et al. 2000;Macoveanu et al. 2007;Chumbley et al. 2008). The...

Summary A gain field, the scaling of a tuned neuronal response by a postural signal, may help support neuronal computation. Here we characterize eye and hand position gain fields in the parietal reach region (PRR). Eye and hand gain fields in individual PRR neurons are similar in magnitude but opposite in sign to one another. This systematic arrangement produces a compound gain field that is proportional to the distance between gaze location and initial hand position. As a result, the visual response to a target for an upcoming reach is scaled by the initial gaze-to-hand distance. Such a scaling is similar to what would be predicted in a neural network that mediates between eye- and hand-centered representations of target location. This systematic arrangement supports a role of PRR in visually-guided reaching and provides strong evidence that gain fields are used for neural computations.

Previous memoranda interfere with working memory. For example, spatial memories are biased toward locations memorized on the previous trial. We predicted, based on attractor network models of memory, that activity in the frontal eye fields (FEFs) encoding a previous target location can persist into the subsequent trial and that this ghost will then bias the readout of the current target. Contrary to this prediction, we find that FEF memory representations appear biased away from (not toward) the previous target location. The behavioral and neural data can be reconciled by a model in which receptive fields of memory neurons converge toward remembered locations, much as receptive fields converge toward attended locations. Convergence increases the resources available to encode the relevant memoranda and decreases overall error in the network, but the residual convergence from the previous trial can give rise to an attractive behavioral bias on the next trial.

According to this prospective, randomized study, anti-inflammatory treatment with colchicine in patients with stable CHF, although effective in reducing inflammation biomarker levels, did not affect in any significant way patient functional status (in terms of New York Heart Association class and objective treadmill exercise tolerance) or the likelihood of death or hospital stay for heart failure.

No abstract