The human imagination: the cognitive neuroscience of visual mental imagery.

Mental imagery can be advantageous, unnecessary and even clinically disruptive. With methodological constraints now overcome, research has shown that visual imagery involves a network of brain areas from the frontal cortex to sensory areas, overlapping with the default mode network, and can function much like a weak version of afferent perception. Imagery vividness and strength range from completely absent (aphantasia) to photo-like (hyperphantasia). Both the anatomy and function of the primary visual cortex are related to visual imagery. The use of imagery as a tool has been linked to many compound cognitive processes and imagery plays both symptomatic and mechanistic roles in neurological and mental disorders and treatments.

Slower but more accurate mental rotation performance in aphantasia linked to differences in cognitive strategies.

Mental rotation tasks are frequently used as standard measures of mental imagery. However, aphantasia research has brought such use into question. Here, we assessed a large group of individuals who lack visual imagery (aphantasia) on two mental rotation tasks: a three-dimensional block-shape, and a human manikin rotation task. In both tasks, those with aphantasia had slower, but more accurate responses than controls. Both groups demonstrated classic linear increases in response time and error-rate as functions of angular disparity. In the three-dimensional block-shape rotation task, a within-group speed-accuracy trade-off was found in controls, whereas faster individuals in the aphantasia group were also more accurate. Control participants generally favoured using object-based mental rotation strategies, whereas those with aphantasia favoured analytic strategies. These results suggest that visual imagery is not crucial for successful performance in classical mental rotation tasks, as alternative strategies can be effectively utilised in the absence of holistic mental representations.

Different Mechanisms for Supporting Mental Imagery and Perceptual Representations: Modulation Versus Excitation.

Recent research suggests imagery is functionally equivalent to a weak form of visual perception. Here we report evidence across five independent experiments on adults that perception and imagery are supported by fundamentally different mechanisms: Whereas perceptual representations are largely formed via increases in excitatory activity, imagery representations are largely supported by modulating nonimagined content. We developed two behavioral techniques that allowed us to first put the visual system into a state of adaptation and then probe the additivity of perception and imagery. If imagery drives similar excitatory visual activity to perception, pairing imagery with perceptual adapters should increase the state of adaptation. Whereas pairing weak perception with adapters increased measures of adaptation, pairing imagery reversed their effects. Further experiments demonstrated that these nonadditive effects were due to imagery weakening representations of nonimagined content. Together these data provide empirical evidence that the brain uses categorically different mechanisms to represent imagery and perception.

The critical role of mental imagery in human emotion: insights from fear-based imagery and aphantasia.

One proposed function of imagery is to make thoughts more emotionally evocative through sensory simulation, which can be helpful both in planning for future events and in remembering the past, but also a hindrance when thoughts become overwhelming and maladaptive, such as in anxiety disorders. Here, we report a novel test of this theory using a special population with no visual imagery: aphantasia. After using multi-method verification of aphantasia, we show that this condition, but not the general population, is associated with a flat-line physiological response (skin conductance levels) to reading and imagining frightening stories. Importantly, we show in a second experiment that this difference in physiological responses to fear-inducing stimuli is not found when perceptually viewing fearful images. These data demonstrate that the aphantasic individuals' lack of a physiological response when imaging scenarios is likely to be driven by their inability to visualize and is not due to a general emotional or physiological dampening. This work provides evidence that a lack of visual imagery results in a dampened emotional response when reading fearful scenarios, providing evidence for the emotional amplification theory of visual imagery.

Comparison of SARS-CoV-2 indirect and direct RT-qPCR detection methods.

BACKGROUND: Sensitive, rapid, and accessible diagnostics continue to be critical to track the COVID-19 pandemic caused by the SARS-CoV-2 virus. RT-qPCR is the gold standard test, and comparison of methodologies and reagents, utilizing patient samples, is important to establish reliable diagnostic pipelines. METHODS: Here, we assessed indirect methods that require RNA extraction with direct RT-qPCR on patient samples. Four different RNA extraction kits (Qiagen, Invitrogen, BGI and Norgen Biotek) were compared. For detection, we assessed two recently developed Taqman-based modules (BGI and Norgen Biotek), a SYBR green-based approach (NEB Luna Universal One-Step Kit) with published and newly-developed primers, and clinical results (Seegene STARMag RNA extraction system and Allplex 2019-nCoV RT-qPCR assay). We also tested and optimized direct, extraction-free detection using these RT-qPCR systems and performed a cost analysis of the different methods evaluated here. RESULTS: Most RNA isolation procedures performed similarly, and while all RT-qPCR modules effectively detected purified viral RNA, the BGI system provided overall superior performance (lower detection limit, lower Ct values and higher sensitivity), generating comparable results to original clinical diagnostic data, and identifying samples ranging from 65 copies to 2.1 × 105 copies of viral genome/µl. However, the BGI detection system is more expensive than other options tested here. With direct RT-qPCR, simply adding an RNase inhibitor greatly improved detection, without the need for any other treatments (e.g. lysis buffers or boiling). The best direct methods detected ~ 10 fold less virus than indirect methods, but this simplified approach reduced sample handling, as well as assay time and cost. CONCLUSIONS: With extracted RNA, the BGI RT-qPCR detection system exhibited superior performance over the Norgen system, matching initial clinical diagnosis with the Seegene Allplex assay. The BGI system was also suitable for direct, extraction-free analysis, providing 78.4% sensitivity. The Norgen system, however, still accurately detected samples with a clinical Ct < 33 from extracted RNA, provided significant cost savings, and was superior to SYBR green assays that exhibited reduced specificity.

Decoding Nonconscious Thought Representations during Successful Thought Suppression.

Controlling our thoughts is central to mental well-being, and its failure is at the crux of a number of mental disorders. Paradoxically, behavioral evidence shows that thought suppression often fails. Despite the broad importance of understanding the mechanisms of thought control, little is known about the fate of neural representations of suppressed thoughts. Using fMRI, we investigated the brain areas involved in controlling visual thoughts and tracked suppressed thought representations using multivoxel pattern analysis. Participants were asked to either visualize a vegetable/fruit or suppress any visual thoughts about those objects. Surprisingly, the content (object identity) of successfully suppressed thoughts was still decodable in visual areas with algorithms trained on imagery. This suggests that visual representations of suppressed thoughts are still present despite reports that they are not. Thought generation was associated with the left hemisphere, and thought suppression was associated with right hemisphere engagement. Furthermore, general linear model analyses showed that subjective success in thought suppression was correlated with engagement of executive areas, whereas thought-suppression failure was associated with engagement of visual and memory-related areas. These results suggest that the content of suppressed thoughts exists hidden from awareness, seemingly without an individual's knowledge, providing a compelling reason why thought suppression is so ineffective. These data inform models of unconscious thought production and could be used to develop new treatment approaches to disorders involving maladaptive thoughts.

Measuring Thought-Control Failure: Sensory Mechanisms and Individual Differences.

The ability to control one's thoughts is crucial for attention, focus, ideation, and mental well-being. Although there is a long history of research into thought control, the inherent subjectivity of thoughts has made objective examination, and thus mechanistic understanding, difficult. Here, we report a novel method to objectively investigate thought-control success and failure by measuring the sensory strength of visual thoughts using binocular rivalry, a perceptual illusion. Across five experiments (N = 67), we found that thought-control failure may occur because of the involuntary and antithetical formation of nonreportable sensory representations during attempts at thought suppression but not during thought substitution. Notably, thought control was worse in individuals with high levels of anxiety and schizotypy but more successful in mindful individuals. Overall, our study offers insight into the underlying mechanisms of thought control and suggests that individual differences play an important role in the ability to control thoughts.

The heterogeneity of mental representation: Ending the imagery debate.

The possible ways that information can be represented mentally have been discussed often over the past thousand years. However, this issue could not be addressed rigorously until late in the 20th century. Initial empirical findings spurred a debate about the heterogeneity of mental representation: Is all information stored in propositional, language-like, symbolic internal representations, or can humans use at least two different types of representations (and possibly many more)? Here, in historical context, we describe recent evidence that humans do not always rely on propositional internal representations but, instead, can also rely on at least one other format: depictive representation. We propose that the debate should now move on to characterizing all of the different forms of human mental representation.

Neural Anatomy of Primary Visual Cortex Limits Visual Working Memory.

Despite the immense processing power of the human brain, working memory storage is severely limited, and the neuroanatomical basis of these limitations has remained elusive. Here, we show that the stable storage limits of visual working memory for over 9 s are bound by the precise gray matter volume of primary visual cortex (V1), defined by fMRI retinotopic mapping. Individuals with a bigger V1 tended to have greater visual working memory storage. This relationship was present independently for both surface size and thickness of V1 but absent in V2, V3 and for non-visual working memory measures. Additional whole-brain analyses confirmed the specificity of the relationship to V1. Our findings indicate that the size of primary visual cortex plays a critical role in limiting what we can hold in mind, acting like a gatekeeper in constraining the richness of working mental function.

Smaller Primary Visual Cortex Is Associated with Stronger, but Less Precise Mental Imagery.

Despite mental imagery's ubiquitous role in human perception, cognition and behavior, one standout question remains unanswered: Why does imagery vary so much from one individual to the next? Here, we used a behavioral paradigm that measures the functional impact of a mental image on subsequent conscious perception and related these measures to the anatomy of the early visual cortex estimated by fMRI retinotopic mapping. We observed a negative relationship between primary visual cortex (V1) surface area and sensory imagery strength, but found positive relationships between V1 and imagery precision (spatial location and orientation). Hence, individuals with a smaller V1 tended to have stronger, but less precise imagery. In addition, subjective vividness of imagery was positively related to prefrontal cortex volume, but unrelated to V1 anatomy. Our findings present the first evidence for the importance of the V1 layout in shaping the strength of human imagination.

Unconscious information changes decision accuracy but not confidence.

The controversial idea that information can be processed and evaluated unconsciously to change behavior has had a particularly impactful history. Here, we extend a simple model of conscious decision-making to explain both conscious and unconscious accumulation of decisional evidence. Using a novel dichoptic suppression paradigm to titrate conscious and unconscious evidence, we show that unconscious information can be accumulated over time and integrated with conscious elements presented either before or after to boost or diminish decision accuracy. The unconscious information could only be used when some conscious decision-relevant information was also present. These data are fit well by a simple diffusion model in which the rate and variability of evidence accumulation is reduced but not eliminated by the removal of conscious awareness. Surprisingly, the unconscious boost in accuracy was not accompanied by corresponding increases in confidence, suggesting that we have poor metacognition for unconscious decisional evidence.

V1 surface size predicts GABA concentration in medial occipital cortex.

A number of recent studies have established a link between behavior and the anatomy of the primary visual cortex (V1). However, one often-raised criticism has been that these studies provide little insight into the mechanisms of the observed relationships. As inhibitory neural interactions have been postulated as an important mechanism for those behaviors related to V1 anatomy, we measured the concentration of inhibitory gamma-amino butyric acid (GABA) in the medial occipital cortex where V1 is located using magnetic resonance spectroscopy (MRS) and estimated the surface area of V1 using fMRI retinotopic mapping. We found a significant positive relationship between GABA concentration and V1 surface area. This relationship was present irrespective of whether the MRS voxel had a fixed size across participants or was proportionally sized to each individual's V1 surface area. Hence, individuals with a larger V1 had a higher GABA concentration in the medial occipital cortex. By tying together V1 size and GABA concentration, our findings point towards individual differences in the level of neural inhibition that might partially mediate the relationships between behavior and V1 neuroanatomy. In addition, they illustrate how stable microscopic properties of neural activity and function are reflected in macro-measures of V1 structure.

Measuring Intuition: Nonconscious Emotional Information Boosts Decision Accuracy and Confidence.

The long-held popular notion of intuition has garnered much attention both academically and popularly. Although most people agree that there is such a phenomenon as intuition, involving emotionally charged, rapid, unconscious processes, little compelling evidence supports this notion. Here, we introduce a technique in which subliminal emotional information is presented to subjects while they make fully conscious sensory decisions. Our behavioral and physiological data, along with evidence-accumulator models, show that nonconscious emotional information can boost accuracy and confidence in a concurrent emotion-free decision task, while also speeding up response times. Moreover, these effects were contingent on the specific predictive arrangement of the nonconscious emotional valence and motion direction in the decisional stimulus. A model that simultaneously accumulates evidence from both physiological skin conductance and conscious decisional information provides an accurate description of the data. These findings support the notion that nonconscious emotions can bias concurrent nonemotional behavior-a process of intuition.

Imagine that: elevated sensory strength of mental imagery in individuals with Parkinson's disease and visual hallucinations.

Visual hallucinations occur when our conscious experience does not accurately reflect external reality. However, these dissociations also regularly occur when we imagine the world around us in the absence of visual stimulation. We used two novel behavioural paradigms to objectively measure visual hallucinations and voluntary mental imagery in 19 individuals with Parkinson's disease (ten with visual hallucinations; nine without) and ten healthy, age-matched controls. We then used this behavioural overlap to interrogate the connectivity both within and between the major attentional control networks using resting-state functional magnetic resonance imaging. Patients with visual hallucinations had elevated mental imagery strength compared with patients without hallucinations and controls. Specifically, the sensory strength of imagery predicted the frequency of visual hallucinations. Together, hallucinations and mental imagery predicted multiple abnormalities in functional connectivity both within and between the attentional control networks, as measured with resting-state functional magnetic resonance imaging. However, the two phenomena were also dissociable at the neural level, with both mental imagery and visual misperceptions associated with specific abnormalities in attentional network connectivity. Our results provide the first evidence of both the shared and unique neural correlates of these two similar, yet distinct phenomena.

Cleavage of the JunB transcription factor by caspases generates a carboxyl-terminal fragment that inhibits activator protein-1 transcriptional activity.

The activator protein-1 (AP-1) family transcription factor, JunB, is an important regulator of proliferation, apoptosis, differentiation, and the immune response. In this report, we show that JunB is cleaved in a caspase-dependent manner in apoptotic anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma cell lines and that ectopically expressed JunB is cleaved in murine RAW 264.7 macrophage cells treated with the NALP1b inflammasome activator, anthrax lethal toxin. In both cases, we identify aspartic acid 137 as the caspase cleavage site and demonstrate that JunB can be directly cleaved in vitro by multiple caspases at this site. Cleavage of JunB at aspartic acid 137 separates the N-terminal transactivation domain from the C-terminal DNA binding and dimerization domains, and we show that the C-terminal cleavage fragment retains both DNA binding activity and the ability to interact with AP-1 family transcription factors. Furthermore, this fragment interferes with the binding of full-length JunB to AP-1 sites and inhibits AP-1-dependent transcription. In summary, we have identified and characterized a novel mechanism of JunB post-translational modification and demonstrate that the C-terminal JunB caspase cleavage product functions as a potent inhibitor of AP-1-dependent transcription.

Expression of granzyme B sensitizes ALK+ ALCL tumour cells to apoptosis-inducing drugs.

BACKGROUND: The serine protease Granzyme B (GzB) is primarily expressed by cytotoxic T lymphocytes and natural killer cells, and functions in allowing these cells to induce apoptosis in virally-infected or transformed cells. Cancers of both lymphoid and non-lymphoid origin also express GzB, and in some cases this expression has been linked to pathogenesis or sensitizing tumour cells to cell death. For example, GzB expression in urothelial carcinoma was implicated in promoting tumour cell invasion, whereas its expression in nasal-type NK/T lymphomas was found to correlate with increased apoptosis. GzB expression is also a hallmark of the non-Hodgkin lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL). Given the fact that ALK+ ALCL exhibits high levels of apoptosis and is typically responsive to conventional chemotherapy, we examined whether GzB expression might play a role in sensitizing ALK+ ALCL tumour cells to apoptosis. METHODS: ALK+ ALCL cell lines stably expressing GzB or non-targeting (control) shRNA were generated and apoptosis was examined by anti-PARP western blotting and terminal deoxynucleotidyl transferase dUTP nick end labelling. Both spontaneous apoptosis and apoptosis in response to treatment with staurosporine or doxorubicin were investigated. In order to assess whether additional granzymes might be important in promoting cell death in ALK+ ALCL, we examined whether other human granzymes were expressed in ALK+ ALCL cell lines using reverse-transcriptase PCR and western blotting. RESULTS: Expression of several GzB shRNAs in multiple ALK+ ALCL cell lines resulted in a significant decrease in GzB levels and activity. While spontaneous apoptosis was similar in ALK+ ALCL cell lines expressing either GzB or control shRNA, GzB shRNA-expressing cells were less sensitive to staurosporine or doxorubicin-induced apoptosis as evidenced by reduced PARP cleavage and decreased DNA fragmentation. Furthermore, we found that GzB is the only granzyme that is expressed at significant levels in ALK+ ALCL cell lines. CONCLUSIONS: Our findings are the first to demonstrate that GzB expression sensitizes ALK+ ALCL cell lines to drug-induced apoptosis. This suggests that GzB expression may be a factor contributing to the favourable response of this lymphoma to treatment.

The sensory strength of voluntary visual imagery predicts visual working memory capacity.

How much we can actively hold in mind is severely limited and differs greatly from one person to the next. Why some individuals have greater capacities than others is largely unknown. Here, we investigated why such large variations in visual working memory (VWM) capacity might occur, by examining the relationship between visual working memory and visual mental imagery. To assess visual working memory capacity participants were required to remember the orientation of a number of Gabor patches and make subsequent judgments about relative changes in orientation. The sensory strength of voluntary imagery was measured using a previously documented binocular rivalry paradigm. Participants with greater imagery strength also had greater visual working memory capacity. However, they were no better on a verbal number working memory task. Introducing a uniform luminous background during the retention interval of the visual working memory task reduced memory capacity, but only for those with strong imagery. Likewise, for the good imagers increasing background luminance during imagery generation reduced its effect on subsequent binocular rivalry. Luminance increases did not affect any of the subgroups on the verbal number working memory task. Together, these results suggest that luminance was disrupting sensory mechanisms common to both visual working memory and imagery, and not a general working memory system. The disruptive selectivity of background luminance suggests that good imagers, unlike moderate or poor imagers, may use imagery as a mnemonic strategy to perform the visual working memory task.

Revisiting the blind mind: Still no evidence for sensory visual imagery in individuals with aphantasia.

The inability to visualise was given the name aphantasia in 2015 by Zeman and colleagues. In 2018 we published research showing that fifteen individuals who self-identified as having aphantasia also demonstrated a lack of sensory visual imagery when undergoing the binocular rivalry imagery paradigm, suggesting more than just a metacognitive difference. Here we update these findings with over fifty participants with aphantasia and show that there is evidence for a lack of sensory imagery in aphantasia. How the binocular rivalry paradigm scores relate to the vividness of visual imagery questionnaire (VVIQ) and how aphantasia can be confirmed is discussed.

Multisensory subtypes of aphantasia: Mental imagery as supramodal perception in reverse.

Cognitive neuroscience research on mental imagery has largely focused on the visual imagery modality in unimodal task contexts. Recent studies have uncovered striking individual differences in visual imagery capacity, with some individuals reporting a subjective absence of conscious visual imagery ability altogether ("aphantasia"). However, naturalistic mental imagery is often multi-sensory, and preliminary findings suggest that many individuals with aphantasia also report a subjective lack of mental imagery in other sensory domains (such as auditory or olfactory imagery). In this paper, we perform a series of cluster analyses on the multi-sensory imagery questionnaire scores of two large groups of aphantasic subjects, defining latent sub-groups in this sample population. We demonstrate that aphantasia is a heterogenous phenomenon characterised by dominant sub-groups of individuals with visual aphantasia (those who report selective visual imagery absence) and multi-sensory aphantasia (those who report an inability to generate conscious mental imagery in any sensory modality). We replicate our findings in a second large sample and show that more unique aphantasia sub-types also exist, such as individuals with selectively preserved mental imagery in only one sensory modality (e.g. intact auditory imagery). We outline the implications of our findings for network theories of mental imagery, discussing how unique aphantasia aetiologies with distinct self-report patterns might reveal alterations to various levels of the sensory processing hierarchy implicated in mental imagery.