Joshua J. LaRocque

Distributed patterns of activity in sensory cortex reflect the precision of multiple items maintained in visual short-term memory.

Traditionally, load sensitivity of sustained, elevated activity has been taken as an index of storage for a limited number of items in visual short-term memory (VSTM). Recently, studies have demonstrated that the contents of a single item held in VSTM can be decoded from early visual cortex, despite the fact that these areas do not exhibit elevated, sustained activity. It is unknown, however, whether the patterns of neural activity decoded from sensory cortex change as a function of load, as one would expect from a region storing multiple representations. Here, we use multivoxel pattern analysis to examine the neural representations of VSTM in humans across multiple memory loads. In an important extension of previous findings, our results demonstrate that the contents of VSTM can be decoded from areas that exhibit a transient response to visual stimuli, but not from regions that exhibit elevated, sustained load-sensitive delay-period activity. Moreover, the neural information present in these transiently activated areas decreases significantly with increasing load, indicating load sensitivity of the patterns of activity that support VSTM maintenance. Importantly, the decrease in classification performance as a function of load is correlated with within-subject changes in mnemonic resolution. These findings indicate that distributed patterns of neural activity in putatively sensory visual cortex support the representation and precision of information in VSTM.

Decoding attended information in short-term memory: An eeg study

For decades it has been assumed that sustained, elevated neural activity—the so-called active trace—is the neural correlate of the short-term retention of information. However, a recent fMRI study has suggested that this activity may be more related to attention than to retention. Specifically, a multivariate pattern analysis failed to find evidence that information that was outside the focus of attention, but nonetheless in STM, was retained in an active state. Here, we replicate and extend this finding by querying the neural signatures of attended versus unattended information within STM with electroencephalograpy (EEG), a method sensitive to oscillatory neural activity to which the previous fMRI study was insensitive. We demonstrate that in the delay-period EEG activity, there is information only about memory items that are also in the focus of attention. Information about items outside the focus of attention is not detectable. This result converges with the fMRI findings to suggest that, contrary to conventional wisdom, an active memory trace may be unnecessary for the short-term retention of information.

Multiple neural states of representation in short-term memory? It’s a matter of attention

Short-term memory (STM) refers to the capacity-limited retention of information over a brief period of time, and working memory (WM) refers to the manipulation and use of that information to guide behavior. In recent years it has become apparent that STM and WM interact and overlap with other cognitive processes, including attention (the selection of a subset of information for further processing) and long-term memory (LTM—the encoding and retention of an effectively unlimited amount of information for a much longer period of time). Broadly speaking, there have been two classes of memory models: systems models, which posit distinct stores for STM and LTM (Atkinson and Shiffrin, 1968; Baddeley and Hitch, 1974); and state-based models, which posit a common store with different activation states corresponding to STM and LTM (Cowan, 1995; McElree, 1996; Oberauer, 2002). In this paper, we will focus on state-based accounts of STM. First, we will consider several theoretical models that postulate, based on considerable behavioral evidence, that information in STM can exist in multiple representational states. We will then consider how neural data from recent studies of STM can inform and constrain these theoretical models. In the process we will highlight the inferential advantage of multivariate, information-based analyses of neuroimaging data (fMRI and electroencephalography (EEG)) over conventional activation-based analysis approaches (Postle, in press). We will conclude by addressing lingering questions regarding the fractionation of STM, highlighting differences between the attention to information vs. the retention of information during brief memory delays.

Reactivation of latent working memories with transcranial magnetic stimulation

A pulse of random activity is sufficient for a brain network to retrieve a dormant activity state. How to reactivate forgotten memories Sophisticated techniques can decode stimulus representations for items held in a persons working memory. However, when subjects shift their attention toward something else, the neural representation of the now unattended item drops to baseline, as though the item has been forgotten. Rose et al. used single-pulse transcranial magnetic stimulation (TMS) to briefly reactivate the representation of an unattended item. A short pulse of TMS enhanced recognition of “forgotten” stimuli, bringing an unattended item back into focal attention. Science, this issue p. 1136 The ability to hold information in working memory is fundamental for cognition. Contrary to the long-standing view that working memory depends on sustained, elevated activity, we present evidence suggesting that humans can hold information in working memory via “activity-silent” synaptic mechanisms. Using multivariate pattern analyses to decode brain activity patterns, we found that the active representation of an item in working memory drops to baseline when attention shifts away. A targeted pulse of transcranial magnetic stimulation produced a brief reemergence of the item in concurrently measured brain activity. This reactivation effect occurred and influenced memory performance only when the item was potentially relevant later in the trial, which suggests that the representation is dynamic and modifiable via cognitive control. The results support a synaptic theory of working memory.

Direct observation of protein folding, aggregation, and a prion-like conformational conversion.

Protein conformational transition from α-helices to β-sheets precedes aggregation of proteins implicated in many diseases, including Alzheimer and prion diseases. Direct characterization of such transitions is often hindered by the complicated nature of the interaction network among amino acids. A recently engineered small protein-like peptide with a simple amino acid composition features a temperature-driven α-helix to β-sheet conformational change. Here we studied the conformational transition of this peptide by molecular dynamics simulations. We observed a critical temperature, below which the peptide folds into an α-helical coiled-coil state and above which the peptide misfolds into β-rich structures with a high propensity to aggregate. The structures adopted by this peptide during low temperature simulations have a backbone root mean square deviation less than 2 Å from the crystal structure. At high temperatures, this peptide adopts an amyloid-like structure, which is mainly composed of coiled anti-parallel β-sheets with the cross-β-signature of amyloid fibrils. Most strikingly, we observed conformational conversions in which an α-helix is converted into a β-strand by proximate stable β-sheets with exposed hydrophobic surfaces and unsaturated hydrogen bonds. Our study suggested a possible generic molecular mechanism of the template-mediated aggregation process, originally proposed by Prusiner (Prusiner, S. B. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 13363-13383) to account for prion infectivity.

Assessing sleep consciousness within subjects using a serial awakening paradigm.

Dreaming—a particular form of consciousness that occurs during sleep—undergoes major changes in the course of the night. We aimed to outline state-dependent features of consciousness using a paradigm with multiple serial awakenings/questionings that allowed for within as well as between subject comparisons. Seven healthy participants who spent 44 experimental study nights in the laboratory were awakened by a computerized sound at 15–30 min intervals, regardless of sleep stage, and questioned for the presence or absence of sleep consciousness. Recall without content (“I was experiencing something but do not remember what”) was considered separately. Subjects had to indicate the content of the most recent conscious experience prior to the alarm sound and to estimate its duration and richness. We also assessed the degree of thinking and perceiving, self- and environment-relatedness and reflective consciousness of the experiences. Of the 778 questionings, 5% were performed during wakefulness, 2% in stage N1, 42% in N2, 33% in N3, and 17% in rapid eye movement (REM) sleep. Recall with content was reported in 34% of non-REM and in 77% of REM sleep awakenings. Sleep fragmentation inherent to the study design appeared to only minimally affect the recall of conscious experiences. Each stage displayed a unique combination of characteristic features of sleep consciousness. In conclusion, our serial awakening paradigm allowed us to collect a large and representative sample of conscious experiences across states of being. It represents a time-efficient method for the study of sleep consciousness that may prove particularly advantageous when combined with techniques such as functional MRI and high-density EEG.

The short- and long-term fates of memory items retained outside the focus of attention.

When a test of working memory (WM) requires the retention of multiple items, a subset of them can be prioritized. Recent studies have shown that, although prioritized (i.e., attended) items are associated with active neural representations, unprioritized (i.e., unattended) memory items can be retained in WM despite the absence of such active representations, and with no decrement in their recognition if they are cued later in the trial. These findings raise two intriguing questions about the nature of the short-term retention of information outside the focus of attention. First, when the focus of attention shifts from items in WM, is there a loss of fidelity for those unattended memory items? Second, could the retention of unattended memory items be accomplished by long-term memory mechanisms? We addressed the first question by comparing the precision of recall of attended versus unattended memory items, and found a significant decrease in precision for unattended memory items, reflecting a degradation in the quality of those representations. We addressed the second question by asking subjects to perform a WM task, followed by a surprise memory test for the items that they had seen in the WM task. Long-term memory for unattended memory items from the WM task was not better than memory for items that had remained selected by the focus of attention in the WM task. These results show that unattended WM representations are degraded in quality and are not preferentially represented in long-term memory, as compared to attended memory items.

The neural correlates of consciousness in sleep: a no-task, within-state paradigm

What are the neural correlates of consciousness? Studies that have addressed this question in the past either compared neural activity during tasks in which subjects report perceiving a stimulus or not, or have contrasted conscious wakefulness with unconscious sleep or anesthesia. However, such contrasts may include correlates of stimulus processing, response preparation or of changes in behavioral state, rather than of consciousness per se. To overcome these limitations, we developed a no-task, within-state paradigm in which sleeping subjects recorded with high density-EEG reported retrospectively whether they had been conscious or not. We identified specific frontal and parieto-occipital regions showing EEG changes several seconds preceding awakenings that distinguished between reports of consciousness and unconsciousness. While decreased parieto-occipital low-frequency activity was associated with highly perceptual experiences, increased frontal high-frequency activity was associated with highly thought-like experiences. Finally, we identified localized, content-specific activations for faces, spatial setting, movement and speech experienced in dreams.Consciousness never fades during wake. However, if awakened from sleep, sometimes we report dreams and sometimes no experiences. Traditionally, dreaming has been identified with REM sleep, characterized by a wake-like, globally ‘activated’, high-frequency EEG. However, dreaming also occurs in NREM sleep, characterized by prominent low-frequency activity. This challenges our understanding of the neural correlates of conscious experiences in sleep. Using high-density EEG, we contrasted the presence and absence of dreaming within NREM and REM sleep. In both NREM and REM sleep, the presence of dreaming was associated with a local decrease in low-frequency activity in posterior cortical regions. High-frequency activity within these regions correlated with specific dream contents. Monitoring this posterior ‘hot zone’ predicted the presence/absence of dreaming during NREM sleep in real time, suggesting that it may constitute a core correlate of conscious experiences in sleep.

Dissociating Perceptual Confidence from Discrimination Accuracy Reveals No Influence of Metacognitive Awareness on Working Memory

Visual awareness is hypothesized to be intimately related to visual working memory (WM), such that information present in WM is thought to have necessarily been represented consciously. Recent work has challenged this longstanding view by demonstrating that visual stimuli rated by observers as unseen can nevertheless be maintained over a delay period. These experiments have been criticized, however, on the basis that subjective awareness ratings may contain response bias (e.g., an observer may report no awareness when in fact they had partial awareness). We mitigated this issue by investigating WM for visual stimuli that were matched for perceptual discrimination capacity (d′), yet which varied in subjective confidence ratings (so-called relative blindsight). If the degree of initial subjective awareness of a stimulus facilitates later maintenance of that information, WM performance should improve for stimuli encoded with higher confidence. In contrast, we found that WM performance did not benefit from higher visual discrimination confidence. This relationship was observed regardless of WM load (1 or 3). Insofar as metacognitive ratings (e.g., confidence, visibility) reflect visual awareness, these results challenge a strong relationship between conscious perception and WM using a paradigm that controls for discrimination accuracy and is less subject to response bias (since confidence is manipulated within subjects). Methodologically, we replicate prior efforts to induce relative blindsight using similar stimulus displays, providing a general framework for isolating metacognitive awareness in order to examine the function of consciousness.

Parietal-occipital interactions underlying control- and representation-related processes in working memory for nonspatial visual features

Although the manipulation of load is popular in visual working memory research, many studies confound general attentional demands with context binding by drawing memoranda from the same stimulus category. In this fMRI study of human observers (both sexes), we created high- versus low-binding conditions, while holding load constant, by comparing trials requiring memory for the direction of motion of one random dot kinematogram (RDK; 1M trials) versus for three RDKs (3M), or versus one RDK and two color patches (1M2C). Memory precision was highest for 1M trials and comparable for 3M and 1M2C trials. And although delay-period activity in occipital cortex did not differ between the three conditions, returning to baseline for all three, multivariate pattern analysis decoding of a remembered RDK from occipital cortex was also highest for 1M trials and comparable for 3M and 1M2C trials. Delay-period activity in intraparietal sulcus (IPS), although elevated for all three conditions, displayed more sensitivity to demands on context binding than to load per se. The 1M-to-3M increase in IPS signal predicted the 1M-to-3M declines in both behavioral and neural estimates of working memory precision. These effects strengthened along a caudal-to-rostral gradient, from IPS0 to IPS5. Context binding-independent load sensitivity was observed when analyses were lateralized and extended into PFC, with trend-level effects evident in left IPS and strong effects in left lateral PFC. These findings illustrate how visual working memory capacity limitations arise from multiple factors that each recruit dissociable brain systems. SIGNIFICANCE STATEMENT Visual working memory capacity predicts performance on a wide array of cognitive and real-world outcomes. At least two theoretically distinct factors are proposed to influence visual working memory capacity limitations: an amodal attentional resource that must be shared across remembered items; and the demands on context binding. We unconfounded these two factors by varying load with items drawn from the same stimulus category (“high demands on context binding”) versus items drawn from different stimulus categories (“low demands on context binding”). The results provide evidence for the dissociability, and the neural bases, of these two theorized factors, and they specify that the functions of intraparietal sulcus may relate more strongly to the control of representations than to the general allocation of attention.