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Sustained neural activity during the delay phase of spatial working memory tasks is compelling evidence for the neural correlate of active storage and maintenance of spatial information, however, it does not provide insight into specific mechanisms of spatial coding. This activity may reflect a range of processes, such as maintenance of a stimulus position or a prepared motor response plan. The aim of our study was to examine neural evidence for the use of different coding strategies, depending on the characteristics and demands of a spatial working memory task. Thirty-one (20 women, 23 ± 5 years) and 44 (23 women, 21 ± 2 years) participants performed a spatial working memory task while we measured their brain activity using fMRI in two separate experiments. Participants were asked to remember the position of a briefly presented target stimulus and, after a delay period, to use a joystick to indicate either the position of the remembered target or an indicated non-matching location. The task was designed so that the predictability of the response could be manipulated independently of task difficulty and memory retrieval process. We were particularly interested in contrasting conditions in which participants (i) could use prospective coding of the motor response or (ii) had to rely on retrospective sensory information. Prospective motor coding was associated with activity in somatomotor, premotor, and motor cortices and increased integration of brain activity with and within the somatomotor network. In contrast, retrospective sensory coding was associated with increased activity in parietal regions and increased functional connectivity with and within secondary visual and dorsal attentional networks. The observed differences in activation levels, dynamics of differences over trial duration, and integration of information within and between brain networks provide compelling evidence for the use of complementary spatial working memory strategies optimized to meet task demands.
RESUMO
Integrating motivational signals with cognition is critical for goal-directed activities. The mechanisms that link neural changes with motivated working memory continue to be understood. Here, we tested how externally cued and non-cued (internally represented) reward and loss impact spatial working memory precision and neural circuits in human subjects using fMRI. We translated the classic delayed-response spatial working memory paradigm from non-human primate studies to take advantage of a continuous numeric measure of working memory precision, and the wealth of translational neuroscience yielded by these studies. Our results demonstrated that both cued and non-cued reward and loss improved spatial working memory precision. Visual association regions of the posterior prefrontal and parietal cortices, specifically the precentral sulcus (PCS) and intraparietal sulcus (IPS), had increased BOLD signal during incentivized spatial working memory. A subset of these regions had trial-by-trial increases in BOLD signal that were associated with better working memory precision, suggesting that these regions may be critical for linking neural signals with motivated working memory. In contrast, regions straddling executive networks, including areas in the dorsolateral prefrontal cortex, anterior parietal cortex and cerebellum displayed decreased BOLD signal during incentivized working memory. While reward and loss similarly impacted working memory processes, they dissociated during feedback when money won or avoided in loss was given based on working memory performance. During feedback, the trial-by-trial amount and valence of reward/loss received was dissociated amongst regions such as the ventral striatum, habenula and periaqueductal gray. Overall, this work suggests motivated spatial working memory is supported by complex sensory processes, and that the IPS and PCS in the posterior frontoparietal cortices may be key regions for integrating motivational signals with spatial working memory precision.
Assuntos
Memória de Curto Prazo , Motivação , Animais , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Memória de Curto Prazo/fisiologia , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , RecompensaRESUMO
Reward processing and cognition are disrupted in schizophrenia (SCZ), yet how these processes interface is unknown. In SCZ, deficits in reward representation may affect motivated, goal-directed behaviors. To test this, we examined the effects of monetary reward on spatial working memory (WM) performance in patients with SCZ. To capture complimentary effects, we tested biophysically grounded computational models of neuropharmacologic manipulations onto a canonical fronto-parietal association cortical microcircuit capable of WM computations. Patients with SCZ (n = 33) and healthy control subjects (HCS; n = 32) performed a spatial WM task with 2 reward manipulations: reward cues presented prior to each trial, or contextually prior to a block of trials. WM performance was compared with cortical circuit models of WM subjected to feed-forward glutamatergic excitation, feed-forward GABAergic inhibition, or recurrent modulation strengthening local connections. Results demonstrated that both groups improved WM performance to reward cues presented prior to each trial (HCS d = -0.62; SCZ d = -1.0), with percent improvement correlating with baseline WM performance (r = .472, p < .001). However, rewards presented contextually before a block of trials did not improve WM performance in patients with SCZ (d = 0.01). Modeling simulations achieved improved WM precision through strengthened local connections via neuromodulation, or feed-forward inhibition. Taken together, this work demonstrates that patients with SCZ can improve WM performance to short-term, but not longer-term rewards-thus, motivated behaviors may be limited by strength of reward representation. A potential mechanism for transiently improved WM performance may be strengthening of local fronto-parietal microcircuit connections via neuromodulation or feed-forward inhibitory drive. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Assuntos
Memória de Curto Prazo/fisiologia , Recompensa , Esquizofrenia , Psicologia do Esquizofrênico , Memória Espacial/fisiologia , Adulto , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Adulto JovemRESUMO
Pupillometry provides an accessible option to track working memory processes with high temporal resolution. Several studies showed that pupil size increases with the number of items held in working memory; however, no study has explored whether pupil size also reflects the quality of working memory representations. To address this question, we used a spatial working memory task to investigate the relationship of pupil size with spatial precision of responses and indicators of reliance on generalized spatial categories. We asked 30 participants (15 female, aged 19-31) to remember the position of targets presented at various locations along a hidden radial grid. After a delay, participants indicated the remembered location with a high-precision joystick providing a parametric measure of trial-to-trial accuracy. We recorded participants' pupil dilations continuously during task performance. Results showed a significant relation between pupil dilation during preparation/early encoding and the precision of responses, possibly reflecting the attentional resources devoted to memory encoding. In contrast, pupil dilation at late maintenance and response predicted larger shifts of responses toward prototypical locations, possibly reflecting larger reliance on categorical representation. On an intraindividual level, smaller pupil dilations during encoding predicted larger dilations during late maintenance and response. On an interindividual level, participants relying more on categorical representation also produced larger precision errors. The results confirm the link between pupil size and the quality of spatial working memory representation. They suggest compensatory strategies of spatial working memory performance-loss of precise spatial representation likely increases reliance on generalized spatial categories.
Assuntos
Memória de Curto Prazo/fisiologia , Pupila/fisiologia , Memória Espacial/fisiologia , Adulto , Feminino , Humanos , Masculino , Desempenho Psicomotor , Adulto JovemRESUMO
Schizophrenia is associated with severe cognitive deficits, including impaired working memory (WM). A neural mechanism that may contribute to WM impairment is the disruption in excitation-inhibition (E/I) balance in cortical microcircuits. It remains unknown, however, how these alterations map onto quantifiable behavioral deficits in patients. Based on predictions from a validated microcircuit model of spatial WM, we hypothesized two key behavioral consequences: i) increased variability of WM traces over time, reducing performance precision; and ii) decreased ability to filter out distractors that overlap with WM representations. To test model predictions, we studied N=27 schizophrenia patients and N=28 matched healthy comparison subjects (HCS) who performed a spatial WM task designed to test the computational model. Specifically, we manipulated delay duration and distractor distance presented during the delay. Subjects used a high-sensitivity joystick to indicate the remembered location, yielding a continuous response measure. Results largely followed model predictions, whereby patients exhibited increased variance and less WM precision as the delay period increased relative to HCS. Schizophrenia patients also exhibited increased WM distractibility, with reports biased toward distractors at specific spatial locations, as predicted by the model. Finally, the magnitude of the WM drift and distractibility were significantly correlated, indicating a possibly shared underlying mechanism. Effects are consistent with elevated E/I ratio in schizophrenia, establishing a framework for translating neural circuit computational model of cognition to human experiments, explicitly testing mechanistic behavioral hypotheses of cellular-level neural deficits in patients.