Double Dissociation Research Articles

Modality-Specific and Amodal Language Processing by Single Neurons.

According to psycholinguistic theories, during language processing, spoken and written words are first encoded along independent phonological and orthographic dimensions, then enter into modality-independent syntactic and semantic codes. Non-invasive brain imaging has isolated several cortical regions putatively associated with those processing stages, but lacks the resolution to identify the corresponding neural codes. Here, we describe the firing responses of over 1000 neurons, and mesoscale field potentials from over 1400 microwires and 1500 iEEG contacts in 21 awake neurosurgical patients with implanted electrodes during written and spoken sentence comprehension. Using forward modeling of temporal receptive fields, we determined which sensory or abstract dimensions are encoded. We observed a double dissociation between superior temporal neurons sensitive to phonemes and phonological features and previously unreported ventral occipito-temporal neurons sensitive to letters and orthographic features. We also discovered novel neurons, primarily located in middle temporal and inferior frontal areas, which are modality-independent and show responsiveness to higher linguistic features. Overall, these findings show how language processing can be linked to neural dynamics, across multiple brain regions at various resolutions and down to the level of single neurons.

Dissecting the causal role of early inferior frontal activation in reading.

Cognitive models of reading assume that speech production occurs after visual and phonological processing of written words. This traditional view is at odds with more recent magnetoencephalography studies showing that the left posterior inferior frontal cortex (pIFC) classically associated with spoken production responds to print at 100-150 ms after word-onset, almost simultaneously with posterior brain regions for visual and phonological processing. Yet the theoretical significance of this fast neural response remains open to date. We used transcranial magnetic stimulation (TMS) to investigate how the left pIFC contributes to the early stage of reading. In Experiment 1, 23 adult participants (14 females) performed three different tasks about written words (oral reading, semantic judgment and perceptual judgment) while single-pulse TMS was delivered to the left pIFC, fusiform gyrus or supramarginal gyrus at different time points (50 to 200 ms after word-onset). A robust double dissociation was found between tasks and stimulation sites - oral reading, but not other control tasks, was disrupted only when TMS was delivered to pIFC at 100 ms. This task-specific impact of pIFC stimulation was further corroborated in Experiment 2, which revealed another double dissociation between oral reading and picture naming. These results demonstrate that the left pIFC specifically and causally mediates rapid computation of speech motor codes at the earliest stage of reading and suggest that this fast sublexical neural pathway for pronunciation, although seemingly dormant, is fully functioning in literate adults. Our results further suggest that these left-hemisphere systems for reading overall act faster than known previously.Significance Statement Recent neuroimaging data suggest that left posterior inferior frontal cortex, classically associated with spoken production, responds to print simultaneously with left fusiform and supramarginal gyri, each responsible for visual and phonological processing, contrary to traditional serial cascade models of reading. While the region is now known to mediate different aspects of cognitive processing, the functional significance of this fast neural response remains unclear. Using transcranial magnetic stimulation, we show that early inferior frontal activation plays a specific and causal role in speeded oral reading at 100 ms after word-onset. This fast sublexical neural pathway for pronunciation, although seemingly dormant, is fully functioning in literate adults. We also propose that the left-hemisphere reading systems act differently and faster than known previously.

“The illuminating quiet”: a metaphor analysis of autobiographical descriptions of inner speech in aphasia

ABSTRACT Background Inner speech in aphasia is a rapidly expanding research area, but can be defined in numerous ways. Unlike behaviourally observable language processes such as overt word-production, inner speech is only directly available to introspection. Subjective experience thus grounds our understanding of inner speech and is a necessary starting point for investigating its definition. Descriptions of inner speech written by people with aphasia can make an important contribution to conceptual clarity in the literature. This important data source has not been systematically analysed. Our research addresses this gap. Aims This research aims to understand the subjective experience of impaired and preserved inner speech in aphasia, through analysis of the metaphors used in autobiographical accounts, and to interpret the findings in relation to the inner speech literature. Methods & Procedures This study carries out a metaphor-led discourse analysis of descriptions of inner speech in four autobiographical accounts of aphasia. Metaphorical expressions describing language processing were identified and coded, then systematic metaphors (i.e. the related concepts which are used consistently to describe a particular topic) were described. The metaphors used to describe inner speech were then analysed, with attention to patterns of use and contextual information. Results & Discussion 338 expressions made use of the main systematic metaphors which were used to describe inner speech. Two types of inner speech- Phonological Inner Speech and Dialogic Inner Speech – were described as distinct and dissociable experiences, and were described using different metaphors. Phonological Inner Speech, the internal activation of phonological representations, as used in mental repetition of a word or phrase, was described by two authors using the metaphors WORDS AS OBJECTS, MIND AS CONTAINER and INNER SPEECH AS HEARING WORDS. Dialogic Inner Speech, the use or awareness of linguistic inner reasoning or dialogue, was described by two different authors using the metaphors INNER SPEECH AS INNER VOICES/PERSONS/MONOLOGUE/DIALOGUE and APHASIA AS SILENCE/FLUID/SPIRITUAL EXPERIENCE. A double dissociation of these different definitions of inner speech is seen across two of the accounts. Different impacts on language processing and cognition were also described. Conclusions This research demonstrates that subjective accounts of inner speech can help clarify theoretical discussions and clinical implications. Although recent research within aphasiology has focused mainly on Phonological Inner Speech, we show that in these accounts the impairment of Dialogic Inner Speech was described as more salient and more explicitly as a “lack of inner voices”.

Differential effects of negative valence and memory type on accuracy, confidence, and metacognitive efficiency

Emotion enhances the subjective experience of recollection. Previous research examined associations between memory accuracy and metamemory confidence judgments, but these studies have not quantified the relationship between accuracy and metacognitive confidence judgments. In this study we utilize signal detection theory frameworks to investigate how memory accuracy (measured by discrimination sensitivity) and the alignment between metamemory confidence judgments and memory accuracy (ie. metacognitive efficiency) varies for neutral and negative valence, as well as item and associative detail memory types. Our results indicate that valence and memory type have different effects on accuracy, confidence, and metacognitive efficiency. Negative valence was associated with enhanced accuracy for both items and associated details, but its relationship with response bias varied across memory types, with conservative recognition responses observed for items and liberal responses for associative details. We also observed a double dissociation between metamemory confidence judgements across valence and memory type with negative valence associated with increased confidence for item memory, but decreased confidence for associated details. Examining the association between memory accuracy and metamemory confidence revealed that metacognitive efficiency was greater for negatively valenced items compared to neutral, but this effect did not generalize to details associated with negatively valenced items. These findings advance our understanding of how arousing, negatively valenced information modulates memory and metacognition.

Unravelling the favorability of radical-directed xn-H2O dissociation at serine and threonine

Among tandem-mass-spectrometry approaches, radical-directed dissociation (RDD) is uniquely sensitive to molecular structure because the location and types of cleavage observed are dictated by radical migration propensities. Although the underlying chemistry for many RDD fragmentation pathways has been previously explained, xn-H2O fragment ions that occur exclusively at serine and threonine residues, have not been examined in detail. Creation of this fragment type inherently requires two dissociation events, one to lose water and another to cleave the peptide backbone. Double dissociations are typically disfavored relative to pathways requiring a single cleavage, yet xn-H2O fragment ions are abundant in RDD spectra. To understand why this fragmentation pathway is favorable, we used a combination of computational chemistry and experiments on peptides with a variety of covalent modifications. Our results explore the energetics, location, and migration of the radical in each step of the mechanism, revealing that favorability can be attributed to the stability of the required radical intermediates and access to low-energy pathways connecting them. Ultimately, the abundant nature of xn-H2O ions and the selectivity associated with their exclusive generation at Ser/Thr provides high value sequence information in RDD experiments.

Teasing apart time reference-related encoding and retrieval deficits in aphasia: evidence from Greek, Russian, Italian and English

ABSTRACT Background Persons with aphasia (PWAs) are often impaired in time reference/tense production. It has been suggested that this impairment is due to encoding or/and retrieval deficits. However, to the best of our knowledge, no experimental design that enables teasing apart selective encoding and retrieval deficits has been proposed thus far. Aims This study aims at disentangling time reference-related encoding deficits from time reference-related retrieval deficits in PWAs. Methods & procedures Two sentence completion tasks tapping production of time reference and subject-verb agreement (control condition) were administered to eight Greek-speaking PWAs, eight Russian-speaking PWAs, six Italian-speaking PWAs, seven English-speaking PWAs and four groups of language-, age- and education-matched healthy controls. Task 1 tapped encoding and retrieval processes to a similar extent. Task 2 predominantly tapped retrieval processes. Comparisons between each PWA and the corresponding control group, as well as within-participant comparisons were performed. Outcomes & results All four control groups performed at ceiling. Twenty-eight out of 29 PWAs were impaired in time reference in at least one of the two completion tasks, and all but three PWAs were impaired in production of subject-verb agreement in at least one of the two tasks. In all language groups, there were PWAs exhibiting between-task dissociations. A double dissociation emerged in the time reference condition, as some Greek-, Russian- and English-speaking PWAs performed better on Task 1 than on Task 2, whereas other Greek- and Italian-speaking PWAs performed worse on Task 1 than on Task 2. In the agreement condition, in each language group, there were PWAs performing better on Task 1 than on Task 2. However, none PWA exhibited the opposite pattern. Based on the results, we identified both PWAs with selective time reference-related encoding deficits and PWAs with selective time reference-related retrieval deficits. Conclusions The present experimental design provides a sound basis for teasing apart selective time reference-related encoding deficits and time reference-related retrieval deficits.

π-Bond Dissociation Energies: C-C, C-N, and C-O.

Single, double, and triple bond dissociation energies are useful quantities, but students and practicing chemists commonly do not know representative values or how they are obtained. In this paper, select π-bond energies are provided and general methods for their determination are discussed. Relationships between heats of hydrogenation, bond dissociation energies, and π-bond strengths are also addressed.

A dopaminergic basis of behavioral control.

Both goal-directed and automatic processes shape human behavior, but these processes often conflict. Behavioral control is the decision about which process guides behavior. Despite the importance of behavioral control for adaptive decision-making, its neural mechanisms remain unclear. Critically, it is unknown if there are mechanisms for behavioral control that are distinct from those supporting the formation of goal-relevant knowledge. We performed deep phenotyping of individual dopamine system function by combining multiple PET scans, fMRI, and dopaminergic drug administration in a within-subject, double-blind, placebo-controlled design. Subjects performed a rule-based response time task, with goal-directed and automatic decision-making operationalized as model-based and model-free influences on behavior. We found a double dissociation between two aspects of ventral striatal dopamine physiology: D2/3 receptor availability and dopamine synthesis capacity. Convergent and causal evidence indicated that D2/3 receptors regulate behavioral control by enhancing model-based and blunting model-free influences on behavior but do not affect model-based knowledge formation. In contrast, dopamine synthesis capacity was linked to the formation of model-based knowledge but not behavioral control. D2/3 receptors also modulated frontostriatal functional connectivity, suggesting they regulate behavioral control by gating prefrontal inputs to the striatum. These results identify central mechanisms underlying individual and state differences in behavioral control and point to striatal D2/3 receptors as targets for interventions for improving goal-directed behavior.

Time reference in French-speaking people with fluent and non-fluent aphasia (part II): a cluster analysis

ABSTRACT Background Tense production is often impaired in people with aphasia (PWA). Interestingly, the literature suggests that not all tenses are affected in the same way, although the pattern of dissociation is still debated in the literature. The heterogeneity of tense production deficits in PWA might partly explain this lack of consensus in the literature. While this heterogeneity has been demonstrated by descriptive statistics or double dissociations in several studies, no study has used cluster analyses to highlight the main patterns of tense dissociation. Furthermore, the factors underlying this heterogeneity have been little explored. Aims Our study aimed to use cluster analyses on tense production performance to (1) identify the main patterns of dissociation between tenses in PWA and (2) explore the clinical (aphasia type and severity) and cognitive (executive disorders and temporality) factors that may underlie these patterns. Methods & procedures Twenty-one French-speaking participants with fluent and non-fluent aphasia completed a verb inflection production task, as well as language and cognitive tests. Cluster analyses were performed on the differences in performance between the tenses on the verb inflection production task. Generalized linear mixed models and nonparametric statistics were used to analyze the effect of tense and its interaction with the clusters, and to compare the clusters on the clinical and cognitive variables. Outcomes & results Cluster analyses revealed two main clusters, one with worse performances in the past and future than in the present (PWA_1 – 70% of the PWA), and the other with worse performances in the past and present than in the future (PWA_2 – 30%). The type and severity of aphasia, and cognitive test performance did not differ between the two clusters. On the other hand, the PWA_2 cluster had a longer time post-onset than the PWA_1 cluster. Conclusions Our results confirm the heterogeneity of verb inflection deficits in PWA. They suggest that most PWA would have difficulties with past and future tenses, questioning the presence of discourse linking in these two tenses. However, a minority of PWA, who are clinically and cognitively indistinguishable from the others, do not follow this pattern. Adopting the strategy of producing a morphologically simple tense in French – future – could explain the high performance in the future tense and the errors in substituting other tenses with the future in this subgroup. Finally, the clinical and research implications of this heterogeneity, in relation to therapies and the lack of consensus in the literature, are discussed.

Multireference calculations on bond dissociation and biradical polycyclic aromatic hydrocarbons as guidance for fractional occupation number weighted density analysis in DFT calculations

This study explores open-shell biradical and polyradical molecular compounds based on extended multireference (MR) methods (MR-configuration interaction with singles and doubles (CISD) and MR-averaged quadratic coupled cluster (AQCC) approach) using the numbers of unpaired densities NU. These results were used to guide the analysis of the fractional occupation number weighted density (FOD) calculated within the finite temperature (FT) density functional theory (DFT) approach. As critical test examples, the dissociation of carbon–carbon (CC) single, double and triple bonds and a benchmark set of polycyclic aromatic hydrocarbons (PAHs) have been chosen. By examining single, double, and triple bond dissociations, we demonstrate the utility and accuracy but also limitations of the FOD analysis for describing these dissociation processes. In significant extension of previous work (Phys Chem Chem Phys 25: 27380–27393), the assessment of FOD applications for different classes of DFT functionals was performed examining the range-separated functionals ωB97XD, ωB97M-V, CAM-B3LYP, LC-ωPBE, and MN12-SX, the hybrid (M06-2X) functional and the double hybrid (B2P-LYP) functional. In all cases, strong correlations between NFOD and NU values are found. The major task was to develop a new linear regression formula for range-separated functionals allowing a convenient determination of the optimal electronic temperature Tel for the FT-DFT calculation. We also established an optimal temperature for the semiempirical extended tight-binding GFN2-xTB method. These findings significantly broaden the applicability of FOD analysis across various DFT functionals and semiempirical methods.

Unusual patterns of codeswitching in an unbalanced bilingual person with aphasia: effects of language and executive functions impairment

ABSTRACT Background Bilingual individuals with aphasia may exhibit unique patterns of language impairment and recovery. While code-switching (CS) is a common feature of bilingual speech, pathological CS following brain damage can provide insights into the neural mechanisms controlling bilingual language processing. Aims This study aimed to examine language impairment and recovery patterns in IZ, an unbalanced Hebrew-English bilingual with non-fluent aphasia, focusing on the unusual CS behavior observed during his subacute phase of recovery. Methods and procedures IZ underwent language and narrative assessments in both languages during the subacute and chronic phases of recovery. Ten cognitive tests were administered to assess various domains of cognitive function. Language performance was evaluated through naming and syntactic processing tasks in L1-Hebrew and L2-English. The frequency and type of CS were analyzed using the matrix language frame model. Outcomes and results During the subacute phase, IZ displayed significant language deficits in both L1-Hebrew and L2-English, with more severe impairment in L1-Hebrew naming and L2-English syntactic processing. He exhibited frequent involuntary CS, primarily using L1-Hebrew as the matrix language while embedding L2-English content words. Cognitive testing revealed reduced performance across multiple domains. In the chronic phase, IZ showed parallel improvements in both languages, particularly in L1-Hebrew naming and L2-English syntactic processing, along with a marked reduction in CS frequency. Conclusions IZ’s case demonstrates a double dissociation between lexical and syntactic processing across L1 and L2. The results suggest that matrix language selection in bilinguals may be governed by distinct neural mechanisms for each language, with specific brain regions responsible for activating lexical representations. Damage to these regions may lead to pathological CS, as observed in this case. This study underscores the importance of understanding bilingual language control mechanisms in aphasia rehabilitation.

Erratum: Pilipenko and Samaha, "Double Dissociation of Spontaneous Alpha-Band Activity and Pupil-Linked Arousal on Additive and Multiplicative Perceptual Gain".

Erratum: Pilipenko and Samaha, "Double Dissociation of Spontaneous Alpha-Band Activity and Pupil-Linked Arousal on Additive and Multiplicative Perceptual Gain".

Mixed in a World of Truth and Lies: List Composition Moderates the Effects of a Lie Fabrication Manipulation on Memory and Metamemory.

Research has shown that list composition moderates the effects of encoding manipulations on memory performance; differential memory performance is observed at distinct levels of the independent variable in mixed lists, but not in pure lists. The current study aims to investigate the effect of list composition on predicted and actual memory performance using a semantic lie fabrication manipulation. In Experiment 1, participants either told the truth or fabricated a lie in response to a set of general knowledge questions in a mixed-list design, made memory predictions for each response, and received a free recall test. Experiments 2A and 2B compared the effect of list composition by employing mixed and pure lists, respectively. The results showed that the lie fabrication led to a metacognitive illusion in mixed lists by inducing a crossed double dissociation between memory and metamemory. Participants produced higher memory performance and lower memory predictions for lies than the truth. In contrast, predicted and actual memory performance were similar for truth and lies in pure lists. These findings contribute to the existing body of knowledge on list composition and have implications for situations where individuals need to maintain and remember their fabricated lies.

Double dissociation of visuomotor interaction mediated by visual feedback during continuous de novo motor learning

While the sensorimotor cortices are central neural substrates for motor control and learning, how the interaction between their subregions with visual cortices contributes to acquiring de novo visuomotor skills is poorly understood. We design a continuous visuomotor task in fMRI where participants control a cursor using their fingers while learning an arbitrary finger-to-cursor mapping. To investigate visuomotor interaction in the de novo motor task, we manipulate visual feedback of a cursor such that they learn to control using fingers under two alternating conditions: online cursor feedback is available or unavailable except when a target is reached. As a result, we find double dissociation of fMRI activity in subregions of the sensorimotor and visual cortices. Specifically, motor and late visual cortices are more active with online cursor feedback, and somatosensory and early visual cortices are more active without online cursor feedback. We also find a significant reduction in functional connectivity between somatosensory cortices and early visual cortices, which is highly correlated with performance improvement. These findings support the distinct interaction between subregions of sensorimotor cortices and visual cortices, while the connectivity analysis highlights the critical role of somatosensory cortices during de novo motor learning.

Evidence from aphasia suggests a bidirectional relationship between inner speech and executive function

Research over the past several decades has revealed that non-linguistic cognitive impairments can appear alongside language deficits in individuals with aphasia. One vulnerable cognitive domain is executive function, an umbrella term for the higher-level cognitive processes that allow us to direct our behavior towards a goal. Studies in healthy adults reveal that executive function abilities are supported by inner speech, the ability to use language silently in one's head. Therefore, inner speech may mediate the connection between language and executive function deficits in individuals with aphasia. Here, we investigated whether inner speech ability may link language and cognitive impairments in 59 adults with chronic, post-stroke aphasia. We used two approaches to measure inner speech: one based on internal retrieval of words and one based on internal retrieval plus silent manipulation of the retrieved phonological forms. Then, we examined relationships between these two approaches to measuring inner speech and five aspects of executive function ability: response inhibition, conflict monitoring/resolution, general task-switching ability, phonological control, and semantic control. We also looked for dissociations between inner speech ability and executive function ability. Our results show tentative relationships between inner speech (across multiple measurement approaches) and all aspects of executive function except for response inhibition. We also found evidence for a double dissociation: many participants show intact executive function despite poor inner speech, and vice versa, so neither process is strictly reliant on the other. We suggest that this work provides preliminary evidence of a bidirectional relationship between inner speech and executive function: inner speech supports some aspects of executive function via internal self-cueing and certain aspects of executive function support performance on complex inner speech tasks.

Transcranial Magnetic Stimulation Facilitates Neural Speech Decoding.

Transcranial magnetic stimulation (TMS) has been widely used to study the mechanisms that underlie motor output. Yet, the extent to which TMS acts upon the cortical neurons implicated in volitional motor commands and the focal limitations of TMS remain subject to debate. Previous research links TMS to improved subject performance in behavioral tasks, including a bias in phoneme discrimination. Our study replicates this result, which implies a causal relationship between electro-magnetic stimulation and psychomotor activity, and tests whether TMS-facilitated psychomotor activity recorded via electroencephalography (EEG) may thus serve as a superior input for neural decoding. First, we illustrate that site-specific TMS elicits a double dissociation in discrimination ability for two phoneme categories. Next, we perform a classification analysis on the EEG signals recorded during TMS and find a dissociation between the stimulation site and decoding accuracy that parallels the behavioral results. We observe weak to moderate evidence for the alternative hypothesis in a Bayesian analysis of group means, with more robust results upon stimulation to a brain region governing multiple phoneme features. Overall, task accuracy was a significant predictor of decoding accuracy for phoneme categories (F(1,135) = 11.51, p < 0.0009) and individual phonemes (F(1,119) = 13.56, p < 0.0003), providing new evidence for a causal link between TMS, neural function, and behavior.

Dissociable Roles of the mPFC-to-VTA Pathway in the Control of Impulsive Action and Risk-Related Decision-Making in Roman High- and Low-Avoidance Rats.

Impulsive action and risk-related decision-making (RDM) are associated with various psychiatric disorders, including drug abuse. Both behavioral traits have also been linked to reduced frontocortical activity and alterations in dopamine function in the ventral tegmental area (VTA). However, despite direct projections from the medial prefrontal cortex (mPFC) to the VTA, the specific role of the mPFC-to-VTA pathway in controlling impulsive action and RDM remains unexplored. We used positron emission tomography with [18F]-fluorodeoxyglucose to evaluate brain metabolic activity in Roman high- (RHA) and low-avoidance (RLA) rats, which exhibit innate differences in impulsive action and RDM. Notably, we used a viral-based double dissociation chemogenetic strategy to isolate, for the first time to our knowledge, the role of the mPFC-to-VTA pathway in controlling these behaviors. We selectively activated the mPFC-to-VTA pathway in RHA rats and inhibited it in RLA rats, assessing the effects on impulsive action and RDM in the rat gambling task. Our results showed that RHA rats displayed higher impulsive action, less optimal decision-making, and lower cortical activity than RLA rats at baseline. Chemogenetic activation of the mPFC-to-VTA pathway reduced impulsive action in RHA rats, whereas chemogenetic inhibition had the opposite effect in RLA rats. However, these manipulations did not affect RDM. Thus, by specifically targeting the mPFC-to-VTA pathway in a phenotype-dependent way, we reverted innate patterns of impulsive action but not RDM. Our findings suggest a dissociable role of the mPFC-to-VTA pathway in impulsive action and RDM, highlighting its potential as a target for investigating impulsivity-related disorders.

Dissociations in perceptual discrimination following selective damage to the dentate gyrus versus CA1 subfield of the hippocampus

The hippocampus (HPC) is well-known for its involvement in declarative (consciously accessible) memory, but there is evidence that it may also play a role in complex perceptual discrimination. Separate research has demonstrated separable contributions of HPC subregions to component memory processes, with the dentate gyrus (DG) required for mnemonic discrimination of similar inputs and the CA1 subfield required for retention and retrieval, but contributions of these subregions to perceptual processes is understudied. The current study examined the nature and extent of a double dissociation between the dentate gyrus (DG) to discrimination processes and CA1 subfield to retention/retrieval by testing two unique individuals with bilateral damage to the DG (case BL) and CA1 (case BR). We tested BL and BR on a wide range of standardized neuropsychological tests to assess information encoding and retention/retrieval and co-opted many measures to assess perceptual discrimination. Compared to normative data, BL exhibited performance below expectations on most measures requiring perceptual discrimination and on measures of encoding but demonstrated intact retention. Conversely, BR showed no difficulties with perceptual discrimination or verbal encoding but exhibited poor verbal retention, as well as poor encoding and retention of spatial/integrative tasks (e.g., object in a location). These results indicate that, despite its prominent role in memory, the DG is necessary for perceptual discrimination and encoding, whereas CA1 is necessary for retention/retrieval and encoding of spatial information. The pattern of results highlights the critical nature of individual case studies in the nuanced understanding of HPC subfield contributions to different memory processes, as well as the utility of repurposing neuropsychological measures to capture individual differences.

Mindfulness Meditation and Placebo Modulate Distinct Multivariate Neural Signatures to Reduce Pain

BackgroundRather than a passive reflection of nociception, pain is shaped by the interplay between one’s experiences, current cognitive-affective states, and expectations. The placebo response, a paradoxical yet reliable phenomenon, is postulated to reduce pain by engaging mechanisms shared with active therapies. It has been assumed that mindfulness meditation, practiced by sustaining nonjudgmental awareness of arising sensory events, merely reflects mechanisms evoked by placebo. Recently, brain-based multivariate pattern analysis has been validated to successfully disentangle nociceptive-specific, negative affective, and placebo-based dimensions of the subjective pain experience. MethodsTo determine whether mindfulness meditation engages distinct brain mechanisms from placebo and sham mindfulness to reduce pain, multivariate pattern analysis pain signatures were applied across 2 randomized clinical trials that employed overlapping psychophysical pain testing procedures (49 °C noxious heat; visual analog pain scales) and distinct functional magnetic resonance imaging techniques (blood oxygen level–dependent; perfusion based). After baseline pain testing, 115 healthy participants were randomized into a 4-session mindfulness meditation (n = 37), placebo-cream conditioning (n = 19), sham mindfulness meditation (n = 20), or book-listening control (n = 39) intervention. After each intervention, noxious heat was administered during functional magnetic resonance imaging and each manipulation. ResultsA double dissociation in the multivariate pattern analysis signatures supporting pain regulation was revealed by mindfulness meditation compared with placebo cream. Mindfulness meditation produced significantly greater reductions in pain intensity and pain unpleasantness ratings and nociceptive-specific and negative affective pain signatures than placebo cream, sham mindfulness meditation, and control interventions. The placebo-cream group significantly lowered the placebo-based signature. ConclusionsMindfulness meditation and placebo engaged distinct and granular neural pain signatures to reduce pain.

Not just phonology: a longitudinal study of dyslexia subtypes based on the distinction between reading accuracy and reading rate

IntroductionPrevious cross-sectional investigations by Shany and colleagues have provided evidence of double dissociation among dyslexics between word reading accuracy and (pure) word reading rate. A rate-disabled subtype (with intact reading accuracy) evinced deficits only in rapid naming (RAN); An accuracy-disabled subtype (with intact reading rate) showed deficits in phonological awareness (PA) and morphological awareness (MA) but not RAN.MethodThe present longitudinal study followed 639 Palestinian Arabic-speaking children from preschool to Grade 1 with the aim of determining (1) whether a dissociation between PA C MA and RAN is apparent among pre-literate preschoolers, (2) whether the PA C MA-disabled subgroup constitutes a mild form of Developmental Language Disorder (DLD), (3) whether our three disabled subgroups (PA C MA-only, RAN-only, and PA C MA-plus-RAN) can be differentiated on preschool early literacy measures and, (4) whether the three at-risk subgroups develop into selectively rate-disabled, accuracy-disabled, or doubly-disabled (accuracy C rate) readers in Grade 1?ResultsOur findings confirmed the existence of two distinct selectively disabled/at-risk subgroups in preschool: a RAN-only subgroup with intact PA and MA and a PA C MA subgroup with broad impairments across language measures but intact RAN. Grade 1 reading data also confirmed that the RAN-disabled subgroup became slow but accurate readers, whereas the PA C MA subgroup developed into inaccurate and slow readers.DiscussionOur study indicates partial dissociation between early dyslexia subtypes, each displaying distinct and non-overlapping cognitive-linguistic profiles in preschool. The study also revealed a strong association between reading accuracy and reading rate among beginning readers. This study emphasizes the importance of considering heterogeneity in reading outcomes as well as multiple oral language skills beyond the well-documented role of PA.