Overt social interaction and resting state in young adult males with autism: core and contextual neural features.

Conversation is an important and ubiquitous social behaviour. Individuals with autism spectrum disorder (autism) without intellectual disability often have normal structural language abilities but deficits in social aspects of communication like pragmatics, prosody, and eye contact. Previous studies of resting state activity suggest that intrinsic connections among neural circuits involved with social processing are disrupted in autism, but to date no neuroimaging study has examined neural activity during the most commonplace yet challenging social task: spontaneous conversation. Here we used functional MRI to scan autistic males (n = 19) without intellectual disability and age- and IQ-matched typically developing control subjects (n = 20) while they engaged in a total of 193 face-to-face interactions. Participants completed two kinds of tasks: conversation, which had high social demand, and repetition, which had low social demand. Autistic individuals showed abnormally increased task-driven interregional temporal correlation relative to controls, especially among social processing regions and during high social demand. Furthermore, these increased correlations were associated with parent ratings of participants' social impairments. These results were then compared with previously-acquired resting state data (56 autism, 62 control subjects). While some interregional correlation levels varied by task or rest context, others were strikingly similar across both task and rest, namely increased correlation among the thalamus, dorsal and ventral striatum, somatomotor, temporal and prefrontal cortex in the autistic individuals, relative to the control groups. These results suggest a basic distinction. Autistic cortico-cortical interactions vary by context, tending to increase relative to controls during task and decrease during test. In contrast, striato- and thalamocortical relationships with socially engaged brain regions are increased in both task and rest, and may be core to the condition of autism.

Fronto-parietal mirror neuron system modeling: Visuospatial transformations support imitation learning independently of imitator perspective.

Although the human mirror neuron system (MNS) is critical for action observation and imitation, most MNS investigations overlook the visuospatial transformation processes that allow individuals to interpret and imitate actions observed from differing perspectives. This problem is not trivial since accurately reaching for and grasping an object requires a visuospatial transformation mechanism capable of precisely remapping fine motor skills where the observer's and imitator's arms and hands may have quite different orientations and sizes. Accordingly, here we describe a novel neural model to investigate the dynamics between the fronto-parietal MNS and visuospatial processes during observation and imitation of a reaching and grasping action. Our model encompasses i) the inferior frontal gyrus (IFG) and inferior parietal lobule (IPL), regions that are postulated to produce neural drive and sensory predictions, respectively; ii) the middle temporal (MT) and middle superior temporal (MST) regions that are postulated to process visual motion of a particular action; and iii) the superior parietal lobule (SPL) and intra-parietal sulcus (IPS) that are hypothesized to encode the visuospatial transformations enabling action observation/imitation based on different visuospatial viewpoints. The results reveal that when a demonstrator executes an action, an imitator can reproduce it with similar kinematics, independently of differences in anthropometry, distance, and viewpoint. As with prior empirical findings, similar model synaptic activity was observed during both action observation and execution along with the existence of both view-independent and view-dependent neural populations in the frontal MNS. Importantly, this work generates testable behavioral and neurophysiological predictions. Namely, the model predicts that i) during observation/imitation the response time increases linearly as the rotation angle of the observed action increases but remain similar when performing both clockwise and counterclockwise rotation and ii) IPL embeds essentially view-independent neurons while SPL/IPS includes both view-independent and view-dependent neurons. Overall, this work suggests that MT/MST visuomotion processes combined with the SPL/IPS allow the MNS to observe and imitate actions independently of demonstrator-imitator spatial relationships.

Sleep extension reduces pain sensitivity.

INTRODUCTION: Insufficient sleep increases pain sensitivity in healthy individuals. Additionally, extending sleep (eg, increasing nocturnal sleep time or adding a mid-day nap) has been shown to restore pain sensitivity to baseline levels in sleep deprived/restricted individuals. Whether sleep extension can reduce pain sensitivity beyond baseline levels in non-sleep restricted/deprived individuals remains unknown. METHODS: In a sample of 27 healthy, pain-free, normally-sleeping individuals (17 males, mean age ∼24 yrs), we examined the impact of five nights of sleep extension on pain sensitivity. Pain threshold (elapsed time until the participant reported pain) and pain tolerance (total time the participant kept the hand submerged in the cold water) were measured using the Cold Pressor Task. Furthermore, we assessed the extent to which self-reported sleep amount in relation to the minimal subjective sleep requirement for adequate performance (sleep credit) was associated with pain sensitivity changes. RESULTS: On average individuals slept almost 2 extra hours per night. Our results indicate that sleep extension increases pain tolerance beyond baseline levels. However, sleep extension did not impact pain threshold. We also found that individuals with a smaller sleep credit (ie, those who habitually obtain less sleep than they feel they need) experienced greater increases in pain tolerance after extending sleep. CONCLUSIONS: The present findings suggest that sleep extension may increase pain tolerance but not pain threshold in healthy individuals who normally sleep the recommended amount. Our findings also support the idea that sleep credit may be a strong indicator of sleep debt in the context of pain sensitivity.

Neural Efficiency in Expert Cognitive-Motor Performers During Affective Challenge.

Skilled individuals demonstrate a spatially localized or relatively lower response in brain activity characterized as neural efficiency when performing within their domain of expertise. Elite athletes are experts in their chosen sport and thus must be not only adept in the motor domain but must be resilient to performing under the stress of high-level competition. Such stability of performance suggests this population processes emotion and mental stress in an adaptive and efficient manner. This study sought to determine if athletes with a history of successful performance under circumstances of mental stress demonstrate neural efficiency during affective challenges compared to age-matched controls. Using functional magnetic resonance imaging, the blood-oxygen level-dependent response was recorded during emotional challenge induced by sport-specific and general unpleasant images. The athletes demonstrated neural efficiency in brain regions critical to emotion regulation (prefrontal cortex) and affect (insula) independently of their domain of expertise, suggesting adaptive processing of negative events and less emotional reactivity to unpleasant stimuli.

Mucolipidosis types II and III and non-syndromic stuttering are associated with different variants in the same genes.

Homozygous mutations in GNPTAB and GNPTG are classically associated with mucolipidosis II (ML II) alpha/beta and mucolipidosis III (ML III) alpha/beta/gamma, which are rare lysosomal storage disorders characterized by multiple pathologies. Recently, variants in GNPTAB, GNPTG, and the functionally related NAGPA gene have been associated with non-syndromic persistent stuttering. In a worldwide sample of 1013 unrelated individuals with non-syndromic persistent stuttering we found 164 individuals who carried a rare non-synonymous coding variant in one of these three genes. We compared the frequency of these variants with those in population-matched controls and genomic databases, and their location with those reported in mucolipidosis. Stuttering subjects displayed an excess of non-synonymous coding variants compared to controls and individuals in the 1000 Genomes and Exome Sequencing Project databases. We identified a total of 81 different variants in our stuttering cases. Virtually all of these were missense substitutions, only one of which has been previously reported in mucolipidosis, a disease frequently associated with complete loss-of-function mutations. We hypothesize that rare non-synonymous coding variants in GNPTAB, GNPTG, and NAGPA may account for as much as 16% of persistent stuttering cases, and that variants in GNPTAB and GNPTG are at different sites and may in general, cause less severe effects on protein function than those in ML II alpha/beta and ML III alpha/beta/gamma.

Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering.

Stuttering is a common, highly heritable neurodevelopmental disorder characterized by deficits in the volitional control of speech. Whole-exome sequencing identified two heterozygous AP4E1 coding variants, c.1549G>A (p.Val517Ile) and c.2401G>A (p.Glu801Lys), that co-segregate with persistent developmental stuttering in a large Cameroonian family, and we observed the same two variants in unrelated Cameroonians with persistent stuttering. We found 23 other rare variants, including predicted loss-of-function variants, in AP4E1 in unrelated stuttering individuals in Cameroon, Pakistan, and North America. The rate of rare variants in AP4E1 was significantly higher in unrelated Pakistani and Cameroonian stuttering individuals than in population-matched control individuals, and coding variants in this gene are exceptionally rare in the general sub-Saharan West African, South Asian, and North American populations. Clinical examination of the Cameroonian family members failed to identify any symptoms previously reported in rare individuals carrying homozygous loss-of-function mutations in this gene. AP4E1 encodes the ε subunit of the heterotetrameric (ε-ß4-µ4-σ4) AP-4 complex, involved in protein sorting at the trans-Golgi network. We found that the µ4 subunit of AP-4 interacts with NAGPA, an enzyme involved in the synthesis of the mannose 6-phosphate signal that targets acid hydrolases to the lysosome and the product of a gene previously associated with stuttering. These findings implicate deficits in intracellular trafficking in persistent stuttering.

Characteristics of Fluency and Speech in Two Families With High Incidences of Stuttering.

PURPOSE: This study presents data from 2 families with high incidence of stuttering, comparing methods of phenotype assignment and exploring the presence of other fluency disorders and corresponding speech characteristics. METHOD: Three methods for assigning phenotype of stuttering were used: self-identification, family identification, and expert identification. Agreement on which individuals were assigned by each of these methods was studied. Multiple measures of fluency and speech production were obtained. RESULTS: Self-reports and descriptions of blocking rather than self-identification as a person who stutters demonstrated the best agreement with expert identification of stuttering. Family identification showed poor agreement with both expert and self-identification of stuttering. Using binary categories of fluent or stuttering, 90% of individuals in 1 family were classified by expert consensus. Only 70% of the other family could be similarly categorized. Experts required 2 other categories, cluttering and other fluency disorders, to fully characterize dysfluency within this family. These 2 families also demonstrated differences in speech production. CONCLUSION: Some families with high incidence of stuttering may also have high incidence of other fluency disorders and other speech-production difficulties. This finding may have ramifications for genetic studies, including criteria for defining phenotype and collapsing data across multiple families.

MEG-based detection and localization of perilesional dysfunction in chronic stroke.

Post-stroke impairment is associated not only with structural lesions, but also with dysfunction in surviving perilesional tissue. Previous studies using equivalent current dipole source localization of MEG/EEG signals have demonstrated a preponderance of slow-wave activity localized to perilesional areas. Recent studies have also demonstrated the utility of nonlinear analyses such as multiscale entropy (MSE) for quantifying neuronal dysfunction in a wide range of pathologies. The current study utilized beamformer-based reconstruction of signals in source space to compare spectral and nonlinear measures of electrical activity in perilesional and healthy cortices. Data were collected from chronic stroke patients and healthy controls, both young and elderly. We assessed relative power in the delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz) and beta (15-30 Hz) frequency bands, and also measured the nonlinear complexity of electrical activity using MSE. Perilesional tissue exhibited a general slowing of the power spectrum (increased delta/theta, decreased beta) as well as a reduction in MSE. All measures tested were similarly sensitive to changes in the posterior perilesional regions, but anterior perilesional dysfunction was detected better by MSE and beta power. The findings also suggest that MSE is specifically sensitive to electrophysiological dysfunction in perilesional tissue, while spectral measures were additionally affected by an increase in rolandic beta power with advanced age. Furthermore, perilesional electrophysiological abnormalities in the left hemisphere were correlated with the degree of language task-induced activation in the right hemisphere. Finally, we demonstrate that single subject spectral and nonlinear analyses can identify dysfunctional perilesional regions within individual patients that may be ideal targets for interventions with noninvasive brain stimulation.

Brain activity and connectivity during poetry composition: Toward a multidimensional model of the creative process.

Creativity, a multifaceted construct, can be studied in various ways, for example, investigating phases of the creative process, quality of the creative product, or the impact of expertise. Previous neuroimaging studies have assessed these individually. Believing that each of these interacting features must be examined simultaneously to develop a comprehensive understanding of creative behavior, we examined poetry composition, assessing process, product, and expertise in a single experiment. Distinct activation patterns were associated with generation and revision, two major phases of the creative process. Medial prefrontal cortex (MPFC) was active during both phases, yet responses in dorsolateral prefrontal and parietal executive systems (DLPFC/IPS) were phase-dependent, indicating that while motivation remains unchanged, cognitive control is attenuated during generation and re-engaged during revision. Experts showed significantly stronger deactivation of DLPFC/IPS during generation, suggesting that they may more effectively suspend cognitive control. Importantly however, similar overall patterns were observed in both groups, indicating the same cognitive resources are available to experts and novices alike. Quality of poetry, assessed by an independent panel, was associated with divergent connectivity patterns in experts and novices, centered upon MPFC (for technical facility) and DLPFC/IPS (for innovation), suggesting a mechanism by which experts produce higher quality poetry. Crucially, each of these three key features can be understood in the context of a single neurocognitive model characterized by dynamic interactions between medial prefrontal areas regulating motivation, dorsolateral prefrontal, and parietal areas regulating cognitive control and the association of these regions with language, sensorimotor, limbic, and subcortical areas distributed throughout the brain.

Personal experience with narrated events modulates functional connectivity within visual and motor systems during story comprehension.

Past experience of everyday life activities, which forms the basis of our knowledge about the world, greatly affects how we understand stories. Yet, little is known about how this influence is instantiated in the human brain. Here, we used functional magnetic resonance imaging to investigate how past experience facilitates functional connectivity during the comprehension of stories rich in perceptual and motor details. We found that comprehenders' past experience with the scenes and actions described in the narratives selectively modulated functional connectivity between lower- and higher-level areas within the neural systems for visual and motor processing, respectively. These intramodal interactions may play an important role in integrating personal knowledge about a narrated situation with an evolving discourse representation. This study provides empirical evidence consistent with the idea that regions related to visual and motor processing are involved in the reenactment of experience as proposed by theories of embodied cognition.

Denoising the speaking brain: toward a robust technique for correcting artifact-contaminated fMRI data under severe motion.

A comprehensive set of methods based on spatial independent component analysis (sICA) is presented as a robust technique for artifact removal, applicable to a broad range of functional magnetic resonance imaging (fMRI) experiments that have been plagued by motion-related artifacts. Although the applications of sICA for fMRI denoising have been studied previously, three fundamental elements of this approach have not been established as follows: 1) a mechanistically-based ground truth for component classification; 2) a general framework for evaluating the performance and generalizability of automated classifiers; and 3) a reliable method for validating the effectiveness of denoising. Here we perform a thorough investigation of these issues and demonstrate the power of our technique by resolving the problem of severe imaging artifacts associated with continuous overt speech production. As a key methodological feature, a dual-mask sICA method is proposed to isolate a variety of imaging artifacts by directly revealing their extracerebral spatial origins. It also plays an important role for understanding the mechanistic properties of noise components in conjunction with temporal measures of physical or physiological motion. The potentials of a spatially-based machine learning classifier and the general criteria for feature selection have both been examined, in order to maximize the performance and generalizability of automated component classification. The effectiveness of denoising is quantitatively validated by comparing the activation maps of fMRI with those of positron emission tomography acquired under the same task conditions. The general applicability of this technique is further demonstrated by the successful reduction of distance-dependent effect of head motion on resting-state functional connectivity.

Neural correlates and network connectivity underlying narrative production and comprehension: a combined fMRI and PET study.

The neural correlates of narrative production and comprehension remain poorly understood. Here, using positron emission tomography (PET), functional magnetic resonance imaging (fMRI), contrast and functional network connectivity analyses we comprehensively characterize the neural mechanisms underlying these complex behaviors. Eighteen healthy subjects told and listened to fictional stories during scanning. In addition to traditional language areas (e.g., left inferior frontal and posterior middle temporal gyri), both narrative production and comprehension engaged regions associated with mentalizing and situation model construction (e.g., dorsomedial prefrontal cortex, precuneus and inferior parietal lobules) as well as neocortical premotor areas, such as the pre-supplementary motor area and left dorsal premotor cortex. Narrative comprehension alone showed marked bilaterality, activating right hemisphere homologs of perisylvian language areas. Narrative production remained predominantly left lateralized, uniquely activating executive and motor-related regions essential to language formulation and articulation. Connectivity analyses revealed strong associations between language areas and the superior and middle temporal gyri during both tasks. However, only during storytelling were these same language-related regions connected to cortical and subcortical motor regions. In contrast, during story comprehension alone, they were strongly linked to regions supporting mentalizing. Thus, when employed in a more complex, ecologically-valid context, language production and comprehension show both overlapping and idiosyncratic patterns of activation and functional connectivity. Importantly, in each case the language system is integrated with regions that support other cognitive and sensorimotor domains.

Decreased connectivity between the thalamus and the neocortex during human nonrapid eye movement sleep.

STUDY OBJECTIVES: To determine whether thalamocortical signaling between the thalamus and the neocortex decreases from wakefulness to nonrapid eye movement (NREM) sleep. DESIGN: Electroencephalography and functional magnetic resonance imaging data were collected simultaneously at 02:30 after 44 h of sleep deprivation. SETTING: Clinical research hospital. PARTICIPANTS: There were six volunteers (mean age 24.2 y, one male) who yielded sufficient amounts of usable, artifact-free data. All were healthy, right-handed native English speakers who consumed less than 710 mL of caffeinated beverages per day. Psychiatric, neurological, circadian, and sleep disorders were ruled out by reviewing each patient's clinical history. A standard clinical nocturnal polysomnogram was negative for sleep disorders. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: A functional connectivity analysis was performed using the centromedian nucleus as the seed region. We determined the statistical significance of the difference between correlations obtained during wakefulness and during slow wave sleep. Neocortical regions displaying decreased thalamic connectivity were all heteromodal regions (e.g., medial frontal gyrus and posterior cingulate/precuneus), whereas there was a complete absence of neocortical regions displaying increased thalamic connectivity. Although more clusters of significant decreases were observed in stage 2 sleep, these results were similar to the results for slow wave sleep. CONCLUSIONS: Results of this study provide evidence of a functional deafferentation of the neocortex during nonrapid eye movement (NREM) sleep in humans. This deafferentation likely accounts for increased sensory awareness thresholds during NREM sleep. Decreased thalamocortical connectivity in regions such as the posterior cingulate/precuneus also are observed in coma and general anesthesia, suggesting that changes in thalamocortical connectivity may act as a universal "control switch" for changes in consciousness that are observed in coma, general anesthesia, and natural sleep.

Embodied comprehension of stories: interactions between language regions and modality-specific neural systems.

The embodied view of language processing proposes that comprehension involves multimodal simulations, a process that retrieves a comprehender's perceptual, motor, and affective knowledge through reactivation of the neural systems responsible for perception, action, and emotion. Although evidence in support of this idea is growing, the contemporary neuroanatomical model of language suggests that comprehension largely emerges as a result of interactions between frontotemporal language areas in the left hemisphere. If modality-specific neural systems are involved in comprehension, they are not likely to operate in isolation but should interact with the brain regions critical to language processing. However, little is known about the ways in which language and modality-specific neural systems interact. To investigate this issue, we conducted a functional MRI study in which participants listened to stories that contained visually vivid, action-based, and emotionally charged content. Activity of neural systems associated with visual-spatial, motor, and affective processing were selectively modulated by the relevant story content. Importantly, when functional connectivity patterns associated with the left inferior frontal gyrus (LIFG), the left posterior middle temporal gyrus (pMTG), and the bilateral anterior temporal lobes (aTL) were compared, both LIFG and pMTG, but not the aTL, showed enhanced connectivity with the three modality-specific systems relevant to the story content. Taken together, our results suggest that language regions are engaged in perceptual, motor, and affective simulations of the described situation, which manifest through their interactions with modality-specific systems. On the basis of our results and past research, we propose that the LIFG and pMTG play unique roles in multimodal simulations during story comprehension.

P600-like positivity and Left Anterior Negativity responses are elicited by semantic reversibility in nonanomalous sentences.

ERPs are commonly elicited by semantic and syntactic violations in sentences, leading to proposals that they reflect neural activity underlying ordinary language comprehension. We examined ERPs in an auditory sentence-picture-matching task, using nonanomalous sentences that were either semantically reversible, (boy pushes girl) or irreversible, (boy eats apple). Timelocked to the end of the critical clause, which occurred in the middle of a longer sentence, we observed an enhanced central-posterior positivity in response to the reversible sentences. The topography of this response is consistent with the P600 potential reported in studies of syntactic anomalies and other manipulations related to sentence structure. Following the end of the sentence, during a memory delay period prior to picture onset, reversible sentences also evoked a protracted anterior negativity, predominantly on the left. This negativity was stronger for sentences containing relative clauses compared to simple active sentences, but did not differ between object-embedded and the less complex subject-embedded clauses. The observation of a P600 occurring selectively in reversible sentences supports the interpretation of that potential as reflecting the syntactic processing of thematic relationships, as irreversible sentences contained alternative cues for thematic roles. The left anterior negativity likely reflects later processes of rehearsal and reanalysis of sentence content in working memory.

Separating lexical-semantic access from other mnemonic processes in picture-name verification.

We present a novel paradigm to identify shared and unique brain regions underlying non-semantic, non-phonological, abstract, audio-visual (AV) memory vs. naming using a longitudinal functional magnetic resonance imaging experiment. Participants were trained to associate novel AV stimulus pairs containing hidden linguistic content. Half of the stimulus pairs were distorted images of animals and sine-wave speech versions of the animal's name. Images and sounds were distorted in such a way as to make their linguistic content easily recognizable only after being made aware of its existence. Memory for the pairings was tested by presenting an AV pair and asking participants to verify if the two stimuli formed a learned pairing. After memory testing, the hidden linguistic content was revealed and participants were tested again on their recollection of the pairings in this linguistically informed state. Once informed, the AV verification task could be performed by naming the picture. There was substantial overlap between the regions involved in recognition of non-linguistic sensory memory and naming, suggesting a strong relation between them. Contrasts between sessions identified left angular gyrus and middle temporal gyrus as key additional players in the naming network. Left inferior frontal regions participated in both naming and non-linguistic AV memory suggesting the region is responsible for AV memory independent of phonological content contrary to previous proposals. Functional connectivity between angular gyrus and left inferior frontal gyrus and left middle temporal gyrus increased when performing the AV task as naming. The results are consistent with the hypothesis that, at the spatial resolution of fMRI, the regions that facilitate non-linguistic AV associations are a subset of those that facilitate naming though reorganized into distinct networks.

Spatial and temporal features of superordinate semantic processing studied with fMRI and EEG.

The relationships between the anatomical representation of semantic knowledge in the human brain and the timing of neurophysiological mechanisms involved in manipulating such information remain unclear. This is the case for superordinate semantic categorization-the extraction of general features shared by broad classes of exemplars (e.g., living vs. non-living semantic categories). We proposed that, because of the abstract nature of this information, input from diverse input modalities (visual or auditory, lexical or non-lexical) should converge and be processed in the same regions of the brain, at similar time scales during superordinate categorization-specifically in a network of heteromodal regions, and late in the course of the categorization process. In order to test this hypothesis, we utilized electroencephalography and event related potentials (EEG/ERP) with functional magnetic resonance imaging (fMRI) to characterize subjects' responses as they made superordinate categorical decisions (living vs. non-living) about objects presented as visual pictures or auditory words. Our results reveal that, consistent with our hypothesis, during the course of superordinate categorization, information provided by these diverse inputs appears to converge in both time and space: fMRI showed that heteromodal areas of the parietal and temporal cortices are active during categorization of both classes of stimuli. The ERP results suggest that superordinate categorization is reflected as a late positive component (LPC) with a parietal distribution and long latencies for both stimulus types. Within the areas and times in which modality independent responses were identified, some differences between living and non-living categories were observed, with a more widespread spatial extent and longer latency responses for categorization of non-living items.

Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from other states of consciousness.

Rapid eye movement (REM) sleep constitutes a distinct "third state" of consciousness, during which levels of brain activity are commensurate with wakefulness, but conscious awareness is radically transformed. To characterize the temporal and spatial features of this paradoxical state, we examined functional interactions between brain regions using fMRI resting-state connectivity methods. Supporting the view that the functional integrity of the default mode network (DMN) reflects "level of consciousness," we observed functional uncoupling of the DMN during deep sleep and recoupling during REM sleep (similar to wakefulness). However, unlike either deep sleep or wakefulness, REM was characterized by a more widespread, temporally dynamic interaction between two major brain systems: unimodal sensorimotor areas and the higher-order association cortices (including the DMN), which normally regulate their activity. During REM, these two systems become anticorrelated and fluctuate rhythmically, in reciprocally alternating multisecond epochs with a frequency ranging from 0.1 to 0.01 Hz. This unique spatiotemporal pattern suggests a model for REM sleep that may be consistent with its role in dream formation and memory consolidation.

Adaptive significance of right hemisphere activation in aphasic language comprehension.

Aphasic patients often exhibit increased right hemisphere activity during language tasks. This may represent takeover of function by regions homologous to the left-hemisphere language networks, maladaptive interference, or adaptation of alternate compensatory strategies. To distinguish between these accounts, we tested language comprehension in 25 aphasic patients using an online sentence-picture matching paradigm while measuring brain activation with MEG. Linguistic conditions included semantically irreversible ("The boy is eating the apple") and reversible ("The boy is pushing the girl") sentences at three levels of syntactic complexity. As expected, patients performed well above chance on irreversible sentences, and at chance on reversible sentences of high complexity. Comprehension of reversible non-complex sentences ranged from nearly perfect to chance, and was highly correlated with offline measures of language comprehension. Lesion analysis revealed that comprehension deficits for reversible sentences were predicted by damage to the left temporal lobe. Although aphasic patients activated homologous areas in the right temporal lobe, such activation was not correlated with comprehension performance. Rather, patients with better comprehension exhibited increased activity in dorsal fronto-parietal regions. Correlations between performance and dorsal network activity occurred bilaterally during perception of sentences, and in the right hemisphere during a post-sentence memory delay. These results suggest that effortful reprocessing of perceived sentences in short-term memory can support improved comprehension in aphasia, and that strategic recruitment of alternative networks, rather than homologous takeover, may account for some findings of right hemisphere language activation in aphasia.