Network structure and dynamics of the mental workspace

The conscious manipulation of mental representations is central to many creative and uniquely human abilities. How does the human brain mediate such flexible mental operations? Here, multivariate pattern analysis of functional MRI data reveals a widespread neural network that performs specific mental manipulations on the contents of visual imagery. Evolving patterns of neural activity within this mental workspace track the sequence of informational transformations carried out by these manipulations. The network switches between distinct connectivity profiles as representations are maintained or manipulated.Albert Einstein described the elements of his scientific thought as “certain signs and more or less clear images which can be ‘voluntarily’ reproduced or combined” (1). Creative thought in science as well as in other domains such as the visual arts, mathematics, music, and dance requires the capacity to manipulate mental representations flexibly. Cognitive scientists refer to this capacity as a “mental workspace” and suggest that it is a key function of consciousness (2) involving the distribution of information among widespread, specialized subdomains (3).How does the human brain mediate these flexible mental operations? Behavioral studies of the mental workspace, such as Shepard and Metzler’s work on mental rotation (4), have found that many mental operations closely resemble their corresponding physical operations. This finding supports the view that the mental workspace can simulate the physical world. Recent work in neuroscience has focused on mental representations instead of operations, showing that the contents of visual perception (5), visual imagery (6), and even dreams (7) can be decoded from activity in visual cortex. These results suggest that the same regions that mediate representations in sensory perception also are involved in mental imagery. However, how the mind can manipulate these representations remains unknown. Many studies have found increased activity in frontal and parietal regions associated with a range of high-level cognitive abilities (8, 9) including mental rotation (10), analogical reasoning (11), working memory (12), and fluid intelligence (13). Together, these findings suggest that a frontoparietal network may form the core of the mental workspace. We therefore hypothesized that operations on visual representations in the mental workspace are realized through the coordinated activity of a distributed network of regions that spans at least the frontal, parietal, and occipital cortices. A strong test of this hypothesis would be to ask whether patterns of neural activity in these regions contain information about specific mental operations and whether these patterns evolve over time as mental representations are manipulated.In the present study, we tested this hypothesis by asking 15 participants to engage in either maintenance or manipulation of visual imagery while we collected functional MRI (fMRI) measurements of their neural activity. As stimuli, we developed 100 abstract parts that could be combined into 2 × 2 figures (Fig. 1 A and C). In a series of trials, participants mentally maintained a set of parts or a whole figure, mentally constructed a set of four parts into a figure, or mentally deconstructed a figure into its four parts (Fig. 1B). Stimuli were presented briefly at the beginning of each trial, followed by a task prompt and a 6-s delay during which the participant performed the indicated mental operation. At the end of the delay, the target output of the operation was presented along with three similar distractors, and the participant indicated the correct target (Fig. 1D). Adjusting the complexity of the stimuli allowed us to equate for task difficulty by maintaining an accuracy of two out of three correct responses for each participant in each of the four conditions (chance would be 1 out of 4 correct; Fig. 1E).Open in a separate windowFig. 1.Experimental design. (A) Parts could be constructed into 2 × 2 figures, and figures could be deconstructed into parts. (B) Participants performed four mental operations on stimuli: construct parts into figure, deconstruct figure into parts, maintain parts, or maintain figure. (C) The stimulus set of 100 abstract parts, ordered from simple to complex. (D) Example of figures. Parts and figures ranged from simple to complex according to an index, d. This index allowed the difficulty of the task to be equated across conditions. (E) Trial schematic. Trials begin with a figure and four unrelated parts presented for 2 s, followed by a task prompt for 1 s consisting of an arrow indicating the figure or the parts and a letter indicating the task. In this case, the participant is instructed to maintain the figure in memory. The task prompt is followed by a 5-s delay period during which no stimulus is shown and the participant performs the indicated operation. Finally, a test screen appears for 2.5 s. Depending on the task, four figures or four sets of parts are presented, and the participant indicates the correct output of the operation.     

Whole exome and whole genome sequencing with dried blood spot DNA without whole genome amplification

Newborn screening (NBS) for rare conditions is performed in all 50 states in the USA. We have partnered with the California Department of Public Health Genetic Disease Laboratory to determine whether sufficient DNA can be extracted from archived dried blood spots (DBS) for next‐generation sequencing in the hopes that next‐generation sequencing can play a role in NBS. We optimized the DNA extraction and sequencing library preparation protocols for residual infant DBS archived over 20 years ago and successfully obtained acceptable whole exome and whole genome sequencing data. This sequencing study using DBS DNA without whole genome amplification prior to sequencing library preparation provides evidence that properly stored residual newborn DBS are a satisfactory source of DNA for genetic studies.