Brain and Behavioral Evidence for Reweighting of Vestibular Inputs with Long-Duration Spaceflight.

Microgravity alters vestibular signaling. In-flight adaptation to altered vestibular afferents is reflected in post-spaceflight aftereffects, evidenced by declines in vestibularly mediated behaviors (e.g., walking/standing balance), until readaptation to Earth's 1G environment occurs. Here we examine how spaceflight affects neural processing of applied vestibular stimulation. We used fMRI to measure brain activity in response to vestibular stimulation in 15 astronauts pre- and post-spaceflight. We also measured vestibularly-mediated behaviors, including balance, mobility, and rod-and-frame test performance. Data were collected twice preflight and four times postflight. As expected, vestibular stimulation at the preflight sessions elicited activation of the parietal opercular area ("vestibular cortex") and deactivation of somatosensory and visual cortices. Pre- to postflight, we found widespread reductions in this somatosensory and visual cortical deactivation, supporting sensory compensation and reweighting with spaceflight. These pre- to postflight changes in brain activity correlated with changes in eyes closed standing balance, and greater pre- to postflight reductions in deactivation of the visual cortices associated with less postflight balance decline. The observed brain changes recovered to baseline values by 3 months postflight. Together, these findings provide evidence for sensory reweighting and adaptive cortical neuroplasticity with spaceflight. These results have implications for better understanding compensation and adaptation to vestibular functional disruption.

Microgravity effects on the human brain and behavior: Dysfunction and adaptive plasticity.

Emerging plans for travel to Mars and other deep space destinations make it critical for us to understand how spaceflight affects the human brain and behavior. Research over the past decade has demonstrated two co-occurring patterns of spaceflight effects on the brain and behavior: dysfunction and adaptive plasticity. Evidence indicates the spaceflight environment induces adverse effects on the brain, including intracranial fluid shifts, gray matter changes, and white matter declines. Past work also suggests that the spaceflight environment induces adaptive neural effects such as sensory reweighting and neural compensation. Here, we introduce a new conceptual framework to synthesize spaceflight effects on the brain, Spaceflight Perturbation Adaptation Coupled with Dysfunction (SPACeD). We review the literature implicating neurobehavioral dysfunction and adaptation in response to spaceflight and microgravity analogues, and we consider pre-, during-, and post-flight factors that may interact with these processes. We draw several instructive parallels with the aging literature which also suggests co-occurring neurobehavioral dysfunction and adaptive processes. We close with recommendations for future spaceflight research, including: 1) increased efforts to distinguish between dysfunctional versus adaptive effects by testing brain-behavioral correlations, and 2) greater focus on tracking recovery time courses.

Neural correlates of multi-day learning and savings in sensorimotor adaptation.

In the present study we evaluated changes in neural activation that occur over the time course of multiple days of sensorimotor adaptation, and identified individual neural predictors of adaptation and savings magnitude. We collected functional MRI data while participants performed a manual adaptation task during four separate test sessions over a three-month period. This allowed us to examine changes in activation and associations with adaptation and savings at subsequent sessions. Participants exhibited reliable savings of adaptation across the four sessions. Brain activity associated with early adaptation increased across the sessions in a variety of frontal, parietal, cingulate, and temporal cortical areas, as well as various subcortical areas. We found that savings was positively associated with activation in several striatal, parietal, and cingulate cortical areas including the putamen, precuneus, angular gyrus, dorsal anterior cingulate cortex (dACC), and cingulate motor area. These findings suggest that participants may learn how to better engage cognitive processes across days, potentially reflecting improvements in action selection. We propose that such improvements may rely on action-value assignments, which previously have been linked to the dACC and striatum. As correct movements are assigned a higher value than incorrect movements, the former are more likely to be performed again.

Multi-day Adaptation and Savings in Manual and Locomotor Tasks.

Using an individual differences approach, we evaluated whether manual and locomotor adaptation are associated in terms of adaptation and savings across days, and whether they rely on shared underlying mechanisms involving visuospatial working memory or visual field dependence. Participants performed a manual and a locomotor adaptation task during 4 separate test sessions over a 3-month period. Reliable adaptation and savings were observed for both tasks. It was further found that higher visuospatial working memory performance and lower visual field dependence scores were associated with faster learning in the manual and locomotor tasks, respectively. Moreover, adaptation rates were correlated between the 2 tasks in the final test session, suggesting that people may gradually be learning something generalizable about the adaptation process.

Working memory for order and the parietal cortex: an event-related functional magnetic resonance imaging study.

Memory for order information has been tied to the frontal lobes, however, parietal activation is observed in many functional neuroimaging studies. Here we report functional magnetic resonance findings from an event-related experiment involving working memory for order. Five letters were presented for storage, followed after a delay by two probe items. Probe items could be separated by zero to three positions in the memory set and subjects had to indicate whether the items were in the correct order. Analyses indicate that activation in left parietal cortex shows a systematic decrease in activation with increasing probe distance. This finding is consistent with an earlier study in which we suggested that parietal cortical regions mediate the representation of order information via magnitude codes.

Object-based attention and object working memory: overlapping processes revealed by selective interference effects in humans.

Human observers can discriminate two attributes from the same object more efficiently than attributes from two different objects even if the retinal locations of the attributes are the same in the single and dual object cases. The single object advantage challenges the spatial spotlight view of attention and suggests that attentional selection can be object based. We report that the single object advantage is reliably reduced when an object working memory task is performed concurrently, whereas concurrent verbal and spatial working memory tasks have no effect. This selective interference effect provides support for the existence of object-based attentional processes that also contribute to the short-term retention of objects in working memory. These results are consistent with the hypothesis that both attentional and memory subsystems are organized along domain-specific lines, and suggest the importance of attention in rehearsal operations. The contributions of inferior temporal and parietal mechanisms that have been implicated in attending to and remembering objects are considered.

Is the dissociability of working memory systems for name identity, visual-object identity, and spatial location maintained in old age?

The dissociability of working memory for name identity (verbal information), visual objects, and spatial location was explored in 3 experiments. Consistent with previous results, the 3 working memory systems were dissociable in younger adults. Both younger and older adults showed involvement of name identity in an object identity task, and older adults showed this involvement in a spatial memory task. Results were interpreted as showing that the systems are generally separable but that involvement of 1 with another is possible and more likely in older adults. A 4th, correlational study showed that there is generalized decline in working memory systems in old age, with the age differences in memory mediated to a moderate extent by age-related differences in speed of processing. It was speculated that the specific, possibly strategic changes are independent of and take place against a backdrop of generalized loss of nervous system integrity.

Age differences in the frontal lateralization of verbal and spatial working memory revealed by PET.

Age-related decline in working memory figures prominently in theories of cognitive aging. However, the effects of aging on the neural substrate of working memory are largely unknown. Positron emission tomography (PET) was used to investigate verbal and spatial short-term storage (3 sec) in older and younger adults. Previous investigations with younger subjects performing these same tasks have revealed asymmetries in the lateral organization of verbal and spatial working memory. Using volume of interest (VOI) analyses that specifically compared activation at sites identified with working memory to their homologous twin in the opposite hemisphere, we show pronounced age differences in this organization, particularly in the frontal lobes: In younger adults, activation is predominantly left lateralized for verbal working memory, and right lateralized for spatial working memory, whereas older adults show a global pattern of anterior bilateral activation for both types of memory. Analyses of frontal subregions indicate that several underlying patterns contribute to global bilaterality in older adults: most notably, bilateral activation in areas associated with rehearsal, and paradoxical laterality in dorsolateral prefrontal sites (DLPFC; greater left activation for spatial and greater right activation for verbal). We consider several mechanisms that could account for these age differences including the possibility that bilateral activation reflects recruitment to compensate for neural decline.

Age differences in behavior and PET activation reveal differences in interference resolution in verbal working memory.

Older adults were tested on a verbal working memory task that used the item-recognition paradigm. On some trials of this task, response-conflict was created by presenting test-items that were familiar but were not members of a current set of items stored in memory. These items required a negative response, but their familiarity biased subjects toward a positive response. Younger subjects show an interference effect on such trials, and this interference is accompanied by activation of a region of left lateral prefrontal cortex. However, there has been no evidence that the activation in this region is causally related to the interference that the subjects exhibit. In the present study, we demonstrate that older adults show more behavioral interference than younger subjects on this task, and they also show no reliable activation at the same lateral prefrontal site. This leads to the conclusion that this prefrontal site is functionally involved in mediating resolution among conflicting responses or among conflicting representations in working memory.

Differential effects of aging on the functions of the corpus callosum.

Several structural imaging studies have revealed atrophy in regions of the corpus callosum due to normal aging. We examined the performance of young and senior adults on 2 behavioral measures of interhemispheric interactions to test for possible functional consequences of callosal decline. In a simple reaction time task, the efficiency of sensorimotor transfer was assessed by comparing response times from conditions that required interhemispheric transfer (e.g., the left hand responding to a right visual field light) to those from conditions that did not require transfer (e.g., the left hand responding to a left visual field light). Older adults were selectively slower when interhemispheric transfer was required. In the second task, participants matched letters presented within the same visual field or in opposite visual fields. This task is thought to index attentional functions of the corpus callosum, in particular, callosal contributions to resource allocation (Banich, 1998). For more difficult tasks, older participants showed a performance advantage on bilateral conditions requiring transfer compared to unilateral conditions that did not require transfer. This advantage equaled or exceeded that observed in younger adults. Together these results suggest that age does not have uniform effects on callosal function. Whereas sensorimotor functions show age-related decline, attentional functions of the corpus callosum may be relatively preserved and assume a more prominent role in the aging brain.

Inhibition in verbal working memory revealed by brain activation.

There are many occasions in which humans and other animals must inhibit the production of some behavior or inhibit the processing of some internal representation. Success in inhibitory processing under normal circumstances can be revealed by the fact that certain brain pathologies render inhibitory processing ineffective. These pathologies often have been associated with damage to frontal cortex, including lateral and inferior aspects. We provide behavioral evidence of a verbal working memory task that, by hypothesis, engaged inhibitory processing, and we show (by using positron emission tomograpny) that the inhibitory processing is associated with a lateral portion of the left prefrontal cortex. The task in which subjects engaged was item-recognition: Four target letters were presented for storage followed, after a brief interval, by a probe letter that could match a target letter or not. On some trials, when the probe did not match a target letter and therefore required a "no" response, the probe had matched a target letter of the previous trial, so on these trials a "yes" response was prepotent and had to be inhibited, by hypothesis. Compared with a condition in which no prepotent response was created, this condition yielded brain activation in left inferior frontal gyrus, in the region of Brodmann's area 45.

Rehearsal in spatial working memory.

This article reports 3 experiments that tested a hypothesis regarding the nature of rehearsal in spatial working memory, one in which discrete shifts of spatial selective attention mediate the maintenance of location-specific representations. Experiment 1 demonstrated increases in visual processing efficiency for locations held in working memory, which suggested that attention was oriented toward these locations. Experiment 2 eliminated key alternative explanations for Experiment 1 by using an identical stimulus display with a nonspatial memory task, and little or no facilitation of processing at memorized locations was found under these conditions. Finally, Experiment 3 showed that spatial working memory was impaired when participants were hindered in their ability to attend to memorized locations. It is argued that these results implicate selective spatial attention as a rehearsal mechanism for spatial working memory.

The role of parietal cortex in verbal working memory.

Neuroimaging studies of normal subjects and studies of patients with focal lesions implicate regions of parietal cortex in verbal working memory (VWM), yet the precise role of parietal cortex in VWM remains unclear. Some evidence (; ) suggests that the parietal cortex mediates the storage of verbal information, but these studies and most previous ones included encoding and retrieval processes as well as storage and rehearsal of verbal information. A recent positron emission tomography (PET) study by isolated storage and rehearsal from other VWM processes and did not find reliable activation in parietal cortex. This result suggests that parietal cortex may not be involved in VWM storage, contrary to previous proposals. However, we report two behavioral studies indicating that some of the verbal material used by may not have required phonological representations in VWM. In addition, we report a PET study that isolated VWM encoding, retrieval, and storage and rehearsal processes in different PET scans and used material likely to require phonological codes in VWM. After subtraction of appropriate controls, the encoding condition revealed no reliable activations; the retrieval condition revealed reliable activations in dorsolateral prefrontal, anterior cingulate, posterior parietal, and extrastriate cortices, and the storage condition revealed reliable activations in dorsolateral prefrontal, inferior frontal, premotor, and posterior parietal cortices, as well as cerebellum. These results suggest that parietal regions are part of a network of brain areas that mediate the short-term storage and retrieval of phonologically coded verbal material.

Object-based facilitation and inhibition from visual orienting in the human split-brain.

Object-based attention was examined in 2 split-brain patients. A precued object could move within a visual field or cross the midline to the opposite field. Normal individuals show an inhibition in detecting signals in the cued object whether it moves within or between fields. Both patients showed this effect when the cued object moved within a visual field. When it crossed the midline into the opposite visual field, however, detection was faster in the cued box. These results reveal both facilitatory and inhibitory effects on attention that are object based and may last for several hundred milliseconds. However, the inhibition requires an intact corpus callosum for interhemispheric transfer, whereas the facilitation is transferred subcortically.

Object-centered neglect for letters: do informational asymmetries play a role?

In a study of right-parietal patients, Behrmann and Moscovitch [Journal of Cognitive Neuroscience, Vol. 6, pp.1-16, 1994] found object-centered left neglect for asymmetrical but not symmetrical letters, leading them to attribute this neglect to the objects' canonical handedness or intrinsic asymmetry. Using a similar task, we find the same results in neurologically intact observers. However, right-sided bias was observed only when the letters were identified. Because asymmetrical letters are distinguished by features on their right sides, we propose that the apparent object-centered bias in normals and in right-parietal patients may arise from attending to identifying features rather than from representational differences between symmetrical and asymmetrical letters.

Auditory cues and inhibition of return: the importance of oculomotor activation.

We studied the effects of eccentric auditory cues to clarify the conditions that evoke inhibition of return (IOR). We found that auditory cues positioned 12 degrees to the left or right of midline failed to produce IOR whereas visual cues produced IOR under the same experimental conditions. The eccentric auditory cues elicited automatic orienting as evidenced by more rapid detection of cued than uncued visual targets at short stimulus onset asynchrony. Yet these same cues did not produce IOR unless observers were required to saccade to the cue and back to center before generating a manual detection response. Thus, under the conditions examined herein automatic orienting was not sufficient to evoke IOR, but oculomotor activation appeared to be essential. The functional significance of IOR and the question of modality-specific orienting processes are considered.

Vertical orienting control: evidence for attentional bias and "neglect" in the intact brain.

Unilateral neglect may be due to attentional bias: an exaggerated tendency to orient in an ipsilesional direction. Likewise, cases of vertical neglect suggest the existence of vertical attentional biases. This article reports evidence of upward biases in neurologically intact observers. In 5 experiments, observers performed a visual line-bisection task by judging the location of a gap along a tachistoscopically presented vertical line. The upward bias was influenced by attentional cues and was stronger in the right visual field than in the left visual field. Instructions designed to foster the use of an object-based, categorical encoding strategy were associated with an upward bias, whereas those fostering spatial, between-object comparisons were not. The results are discussed in terms of hemispheric differences in attention and specializations along the dorsal-ventral axis of the brain that influence directional orienting.

What is inhibited in inhibition of return?

Research on temporal-order judgments, reference frames, discrimination tasks, and links to oculomotor control suggest important differences between inhibition of return (IOR) and attentional costs and benefits. Yet, it is generally assumed that IOR is an attentional effect even though there is little supporting evidence. The authors evaluated this assumption by examining how several factors that are known to influence attentional costs and benefits affect the magnitude of IOR: target modality, target intensity, and response mode. Results similar to those previously reported for attention were observed: IOR was greater for visual than for auditory targets, showed an inverse relationship with target intensity, and was equivalent for manual and saccadic responses. Important parallels between IOR and attentional costs and benefits are indicated, suggesting that, like attention, IOR may in part affect sensory-perceptual processes.

Object-centered attentional biases in the intact brain.

Abstract By simulating neglect-like effects in neurologically intact observers, we evaluated whether normal attentional allocation can be object centered. In a series of three experiments, observers detected a small gap on the left or right side of a configuration presented in either the left of right visual field. The figures were positioned so that on different trials, the left and right sides would fall in the same retinotopic, hemispatial, and environmental location. Thus, only the location with respect to an object-centered frame varied. We found opposite patterns of bias within each visual field: For figures in the left visual field, left gaps were detected better than right gaps, whereas in the right visual field the opposite pattern was evident. Control conditions indicate that these biases are not due to masking from eccentric contours and depend on the left and right segments being united into a single form. These results indicate that opposing orientational biases of the left and right hemispheres can operate within an object-centered frame in the normal brain. This evidence converges with patient studies and single-unit electrophysiology to reveal the importance of a relatively late, abstract locus for visual selection.

Are microsaccades responsible for the gap effect?

Extinguishing a fixation point shortly before, or concurrently with, the onset of a peripheral visual target reduces the latency of saccades to that target. Saslow (1967) hypothesized that this gap effect might occur because fixation point offsets reduce the incidence of corrective microsaccades with an associated saccadic refractory period. In the present study, a robust gap effect was obtained. However, using a Purkinje image eyetracker with 1 arcmin of resolution, we found that fixation point offsets had no effect on the occurrence of microsaccades and that the occurrence of microsaccades had no impact on the magnitude of gap effect. Microsaccades therefore do not appear to play any part in the production of the gap effect.