The Importance of Semantic Network Brain Regions in Integrating Prior Knowledge with an Ongoing Dialogue.

To understand a dialogue, we need to know the topics that are being discussed. This enables us to integrate our knowledge of what was said previously to interpret the current dialogue. This study involved a large-scale behavioral experiment conducted online and a separate fMRI experiment, both testing human participants. In both, we selectively manipulated knowledge about the narrative content of dialogues presented in short videos. The clips were scenes from situation comedies that were split into two parts. The speech in the part 1 clips could either be presented normally or spectrally rotated to render it unintelligible. The part 2 clips that concluded the scenes were always presented normally. The behavioral experiment showed that knowledge of the preceding narrative boosted memory for the part 2 clips as well as increased the intersubject semantic similarity of recalled descriptions of the dialogues. The fMRI experiment replicated the finding that prior knowledge improved memory for the conclusions of the dialogues. Furthermore, prior knowledge strengthened temporal intersubject correlations in brain regions including the left angular gyrus and inferior frontal gyrus. Together, these findings show that (1) prior knowledge constrains the interpretation of a dialogue to be more similar across individuals; and (2), consistent with this, the activation of brain regions involved in semantic control processing is also more similar between individuals who share the same prior knowledge. Processing in these regions likely supports the activation and integration of prior knowledge, which helps people to better understand and remember dialogues as they unfold.

Activation of Person Knowledge in Medial Prefrontal Cortex during the Encoding of New Lifelike Events.

Our knowledge about people can help us predict how they will behave in particular situations and interpret their actions. In this study, we investigated the cognitive and neural effects of person knowledge on the encoding and retrieval of novel life-like events. Healthy human participants learnt about two characters over a week by watching 6 episodes of one of two situation comedies, which were both centered on a young couple. In the scanner, they watched and then silently recalled 20 new scenes from both shows that were all set in unfamiliar locations: 10 from their trained show and 10 from the untrained show. After scanning, participants' recognition memory was better for scenes from the trained show. The functional magnetic resonance imaging (fMRI) patterns of brain activity when watching the videos were reinstated during recall, but this effect was not modulated by training. However, person knowledge boosted the similarity in fMRI patterns of activity in the medial prefrontal cortex (MPFC) when watching the new events involving familiar characters. Our findings identify a role for the MPFC in the representation of schematic person knowledge during the encoding of novel, lifelike events.

The brain regions supporting schema-related processing of people's identities.

Schematic knowledge about people helps us to understand their behaviour in novel situations. The ventromedial prefrontal cortex (vmPFC) and hippocampus play important, yet poorly understood, roles in schema-based processing. Here, we manipulated schematic knowledge by familiarizing participants over the course of a week to the two lead characters of one of two TV shows. Then during MRI scanning, they viewed pictures of all four characters and performed a recognition memory test afterwards. Memory was also tested for short videos. Schematic knowledge boosted performance on both memory tests. Whole-brain analyses revealed knowledge related activation increases in the vmPFC and retrosplenial cortex while a similar effect was identified in a hippocampal region-of-interest. Representational similarity analyses identified person-specific patterns of activity in the vmPFC but not hippocampus, but no effect of familiarization. Our findings suggest complementary roles for the vmPFC and hippocampus in processing schematic knowledge that was acquired in a naturalistic manner.

Effects of amnesia on processing in the hippocampus and default mode network during a naturalistic memory task: A case study.

Despite their severely impaired episodic memory, individuals with amnesia are able to comprehend ongoing events. Online representations of a current event are thought to be supported by a network of regions centred on the posterior midline cortex (PMC). By contrast, episodic memory is widely believed to be supported by interactions between the hippocampus and these cortical regions. In this MRI study, we investigated the encoding and retrieval of real life-like events (video clips) in a patient with severe amnesia likely resulting from a stroke to the right (and possibly the left) thalamus, and a group of 20 age-matched controls. Structural MRI revealed grey matter reductions in left hippocampus and left thalamus in comparison to controls. We first characterised the regions activated in the controls while they watched and retrieved the videos. There were no differences in activation between the patient and controls in any of the regions. We then identified a widespread network of brain regions, including the hippocampus, that were functionally connected with the PMC in controls. However, in the patient there was a specific reduction in functional connectivity between the PMC and a region of left hippocampus when both watching and attempting to retrieve the videos. A follow up analysis of the control group revealed that, when watching the videos, the functional connectivity between these two regions was correlated with memory performance. Taken together, these findings support the view that the interactions between the PMC and the hippocampus enable the encoding and retrieval of naturalistic events.

Multiscale Integration of Contextual Information During a Naturalistic Task.

Everyday experience requires rapid and automatic integration of incoming stimuli with previously stored knowledge. Prior knowledge can help to construct a general "situation model" of the event, as well as aid comprehension of an ongoing narrative. Using fMRI in healthy adult humans, we investigated processing of videos whose locations and characters were always familiar but whose narratives were either a continuation or noncontinuation of an earlier video (high context (HC) or low context (LC), respectively). Responses in parahippocampal gyrus and retrosplenial cortex were composed of an initial transient, locked to the video onsets, followed by a period of lower amplitude activation that was greater in the LC condition. This may reflect rapid processing of core components of situation models such as location and characters and more gradual incorporation of their narrative themes. By contrast, activity increases in left hemisphere middle temporal gyrus (MTG), angular gyrus, and inferior frontal gyrus were maintained throughout the videos and were higher for HC versus LC videos. Further, activity in the left MTG peaked earlier in the HC condition. We suggest that these regions support representations of the specific interlinked concepts necessary to comprehend an ongoing narrative, which are already established for the HC videos.

Reinstatement of memory representations for lifelike events over the course of a week.

When we remember an event, the content of that memory is represented across the brain. Detailed memory retrieval is thought to involve the reinstatement of those representations. Functional MRI combined with representational similarity analyses (RSA) of spatial patterns of brain activity has revealed reinstatement of recently-experienced events throughout a core memory retrieval network. In the present study, participants were scanned while they watched, immediately retrieved and then retrieved after a week, 24 short videos. Following the delayed retrieval, they freely recalled all videos outside of the scanner. We observed widespread within- and between-subject reinstatement effects within a posterior midline core memory retrieval network during all phases of the experiment. Within precuneus, bilateral middle temporal gyrus and the left hippocampus, reinstatement effects between the retrieval phases correlated with memory performance. These findings extend previous studies that have only employed short retention periods or highly rehearsed materials, demonstrating that memory representations for unique events are reliably reinstated over longer timeframes that are meaningful in the context of real-world episodic memory.

Sources of Phoneme Errors in Repetition: Perseverative, Neologistic, and Lesion Patterns in Jargon Aphasia.

This study examined patterns of neologistic and perseverative errors during word repetition in fluent Jargon aphasia. The principal hypotheses accounting for Jargon production indicate that poor activation of a target stimulus leads to weakly activated target phoneme segments, which are outcompeted at the phonological encoding level. Voxel-lesion symptom mapping studies of word repetition errors suggest a breakdown in the translation from auditory-phonological analysis to motor activation. Behavioral analyses of repetition data were used to analyse the target relatedness (Phonological Overlap Index: POI) of neologistic errors and patterns of perseveration in 25 individuals with Jargon aphasia. Lesion-symptom analyses explored the relationship between neurological damage and jargon repetition in a group of 38 aphasia participants. Behavioral results showed that neologisms produced by 23 jargon individuals contained greater degrees of target lexico-phonological information than predicted by chance and that neologistic and perseverative production were closely associated. A significant relationship between jargon production and lesions to temporoparietal regions was identified. Region of interest regression analyses suggested that damage to the posterior superior temporal gyrus and superior temporal sulcus in combination was best predictive of a Jargon aphasia profile. Taken together, these results suggest that poor phonological encoding, secondary to impairment in sensory-motor integration, alongside impairments in self-monitoring result in jargon repetition. Insights for clinical management and future directions are discussed.

Phonological and semantic processing during comprehension in Wernicke's aphasia: An N400 and Phonological Mapping Negativity Study.

Comprehension impairments in Wernicke's aphasia are thought to result from a combination of impaired phonological and semantic processes. However, the relationship between these cognitive processes and language comprehension has only been inferred through offline neuropsychological tasks. This study used ERPs to investigate phonological and semantic processing during online single word comprehension. EEG was recorded in a group of Wernicke's aphasia n=8 and control participants n=10 while performing a word-picture verification task. The N400 and Phonological Mapping Negativity/Phonological Mismatch Negativity (PMN) event-related potential components were investigated as an index of semantic and phonological processing, respectively. Individuals with Wernicke's aphasia displayed reduced and inconsistent N400 and PMN effects in comparison to control participants. Reduced N400 effects in the WA group were simulated in the control group by artificially degrading speech perception. Correlation analyses in the Wernicke's aphasia group found that PMN but not N400 amplitude was associated with behavioural word-picture verification performance. The results confirm impairments at both phonological and semantic stages of comprehension in Wernicke's aphasia. However, reduced N400 responses in Wernicke's aphasia are at least partially attributable to earlier phonological processing impairments. The results provide further support for the traditional model of Wernicke's aphasia which claims a causative link between phonological processing and language comprehension impairments.

Unmasking Language Lateralization in Human Brain Intrinsic Activity.

Lateralization of function is a fundamental feature of the human brain as exemplified by the left hemisphere dominance of language. Despite the prominence of lateralization in the lesion, split-brain and task-based fMRI literature, surprisingly little asymmetry has been revealed in the increasingly popular functional imaging studies of spontaneous fluctuations in the fMRI BOLD signal (so-called resting-state fMRI). Here, we show the global signal, an often discarded component of the BOLD signal in resting-state studies, reveals a leftward asymmetry that maps onto regions preferential for semantic processing in left frontal and temporal cortex and the right cerebellum and a rightward asymmetry that maps onto putative attention-related regions in right frontal, temporoparietal, and parietal cortex. Hemispheric asymmetries in the global signal resulted from amplitude modulation of the spontaneous fluctuations. To confirm these findings obtained from normal, healthy, right-handed subjects in the resting-state, we had them perform 2 semantic processing tasks: synonym and numerical magnitude judgment and sentence comprehension. In addition to establishing a new technique for studying lateralization through functional imaging of the resting-state, our findings shed new light on the physiology of the global brain signal.

Consolidation of Complex Events via Reinstatement in Posterior Cingulate Cortex.

It is well-established that active rehearsal increases the efficacy of memory consolidation. It is also known that complex events are interpreted with reference to prior knowledge. However, comparatively little attention has been given to the neural underpinnings of these effects. In healthy adults humans, we investigated the impact of effortful, active rehearsal on memory for events by showing people several short video clips and then asking them to recall these clips, either aloud (Experiment 1) or silently while in an MRI scanner (Experiment 2). In both experiments, actively rehearsed clips were remembered in far greater detail than unrehearsed clips when tested a week later. In Experiment 1, highly similar descriptions of events were produced across retrieval trials, suggesting a degree of semanticization of the memories had taken place. In Experiment 2, spatial patterns of BOLD signal in medial temporal and posterior midline regions were correlated when encoding and rehearsing the same video. Moreover, the strength of this correlation in the posterior cingulate predicted the amount of information subsequently recalled. This is likely to reflect a strengthening of the representation of the video's content. We argue that these representations combine both new episodic information and stored semantic knowledge (or "schemas"). We therefore suggest that posterior midline structures aid consolidation by reinstating and strengthening the associations between episodic details and more generic schematic information. This leads to the creation of coherent memory representations of lifelike, complex events that are resistant to forgetting, but somewhat inflexible and semantic-like in nature.

The interference effect in arithmetic fact solving: An fMRI study.

Some multiplication facts share common digits with other, previously learned facts, and as a result, different problems are associated with different levels of interference. The detrimental effect of interference in arithmetic facts knowledge has been recently highlighted in behavioral studies, in children as well as in adults, both in typical and atypical development. The present study investigated the brain regions involved in the interference effect when solving multiplication problems. Twenty healthy adults carried out a multiplication task in an MRI scanner. The event-related design comprised problems whose interference level and problem size were manipulated in a 2×2 factorial design. After each trial, individuals were requested to indicate whether they solved the trial by retrieving the answer from long-term memory. This allowed us to examine which brain areas were sensitive to the interference effect and problem size effect as well as the retrieval strategy. The results highlighted two specific regions: the left angular gyrus was more activated for low interfering than for high interfering problems, and the right intraparietal sulcus was more activated for large problems than for small problems. In both regions, brain activity was not modulated by the other effect. These results suggest that the left angular gyrus is sensitive to the level of interference of the multiplication problems, whereas previously this region was thought to be more activated by small problems or by retrieval strategy. Here, in a design manipulating interference and problem size, while controlling for retrieval strategy, we showed that it rather reflects an automatic mapping between the problem and the answer stored in long-term memory. The right intraparietal sulcus was modulated by the problem size effect, which supports the idea that the problem size effect comes from the higher overlap between magnitude of the answers of large problems compared to small ones. Importantly, neither effects can be reduced to a strategy effect since they were present when analyzing only retrieval trials.

The influence of age and mild cognitive impairment on associative memory performance and underlying brain networks.

Associative memory is essential to everyday activities, such as the binding of faces and corresponding names to form single bits of information. However, this ability often becomes impaired with increasing age. The most important neural substrate of associative memory is the hippocampus, a structure crucially implicated in the pathogenesis of Alzheimer's disease (AD). The main aim of this study was to compare neural correlates of associative memory in healthy aging and mild cognitive impairment (MCI), an at-risk state for AD. We used fMRI to investigate differences in brain activation and connectivity between young controls (n = 20), elderly controls (n = 32) and MCI patients (n = 21) during associative memory retrieval. We observed lower hippocampal activation in MCI patients than control groups during a face-name recognition task, and the magnitude of this decrement was correlated with lower associative memory performance. Further, increased activation in precentral regions in all older adults indicated a stronger involvement of the task positive network (TPN) with age. Finally, functional connectivity analysis revealed a stronger link of hippocampal and striatal components in older adults in comparison to young controls, regardless of memory impairment. In elderly controls, this went hand-in-hand with a stronger activation of striatal areas. Increased TPN activation may be linked to greater reliance on cognitive control in both older groups, while increased functional connectivity between the hippocampus and the striatum may suggest dedifferentiation, especially in elderly controls.

Mismatch negativity (MMN) reveals inefficient auditory ventral stream function in chronic auditory comprehension impairments.

BACKGROUND: Auditory discrimination is significantly impaired in Wernicke's aphasia (WA) and thought to be causatively related to the language comprehension impairment which characterises the condition. This study used mismatch negativity (MMN) to investigate the neural responses corresponding to successful and impaired auditory discrimination in WA. METHODS: Behavioural auditory discrimination thresholds of consonant-vowel-consonant (CVC) syllables and pure tones (PTs) were measured in WA (n = 7) and control (n = 7) participants. Threshold results were used to develop multiple deviant MMN oddball paradigms containing deviants which were either perceptibly or non-perceptibly different from the standard stimuli. MMN analysis investigated differences associated with group, condition and perceptibility as well as the relationship between MMN responses and comprehension (within which behavioural auditory discrimination profiles were examined). RESULTS: MMN waveforms were observable to both perceptible and non-perceptible auditory changes. Perceptibility was only distinguished by MMN amplitude in the PT condition. The WA group could be distinguished from controls by an increase in MMN response latency to CVC stimuli change. Correlation analyses displayed a relationship between behavioural CVC discrimination and MMN amplitude in the control group, where greater amplitude corresponded to better discrimination. The WA group displayed the inverse effect; both discrimination accuracy and auditory comprehension scores were reduced with increased MMN amplitude. In the WA group, a further correlation was observed between the lateralisation of MMN response and CVC discrimination accuracy; the greater the bilateral involvement the better the discrimination accuracy. CONCLUSIONS: The results from this study provide further evidence for the nature of auditory comprehension impairment in WA and indicate that the auditory discrimination deficit is grounded in a reduced ability to engage in efficient hierarchical processing and the construction of invariant auditory objects. Correlation results suggest that people with chronic WA may rely on an inefficient, noisy right hemisphere auditory stream when attempting to process speech stimuli.

The anterior temporal lobes support residual comprehension in Wernicke's aphasia.

Wernicke's aphasia occurs after a stroke to classical language comprehension regions in the left temporoparietal cortex. Consequently, auditory-verbal comprehension is significantly impaired in Wernicke's aphasia but the capacity to comprehend visually presented materials (written words and pictures) is partially spared. This study used functional magnetic resonance imaging to investigate the neural basis of written word and picture semantic processing in Wernicke's aphasia, with the wider aim of examining how the semantic system is altered after damage to the classical comprehension regions. Twelve participants with chronic Wernicke's aphasia and 12 control participants performed semantic animate-inanimate judgements and a visual height judgement baseline task. Whole brain and region of interest analysis in Wernicke's aphasia and control participants found that semantic judgements were underpinned by activation in the ventral and anterior temporal lobes bilaterally. The Wernicke's aphasia group displayed an 'over-activation' in comparison with control participants, indicating that anterior temporal lobe regions become increasingly influential following reduction in posterior semantic resources. Semantic processing of written words in Wernicke's aphasia was additionally supported by recruitment of the right anterior superior temporal lobe, a region previously associated with recovery from auditory-verbal comprehension impairments. Overall, the results provide support for models in which the anterior temporal lobes are crucial for multimodal semantic processing and that these regions may be accessed without support from classic posterior comprehension regions.

How Shakespeare tempests the brain: neuroimaging insights.

Shakespeare made extensive use of the functional shift (FS), a rhetorical device involving a change in the grammatical status of words, e.g., using nouns as verbs. Previous work using event-related brain potentials showed how FS triggers a surprise effect inviting mental re-evaluation, seemingly independent of semantic processing. Here, we used functional magnetic resonance imaging to investigate brain activation in participants making judgements on the semantic relationship between sentences -some containing a Shakespearean FS- and subsequently presented words. Behavioural performance in the semantic decision task was high and unaffected by sentence type. However, neuroimaging results showed that sentences featuring FS elicited significant activation beyond regions classically activated by typical language tasks, including the left caudate nucleus, the right inferior frontal gyrus and the right inferior temporal gyrus. These findings show how Shakespeare's grammatical exploration forces the listener to take a more active role in integrating the meaning of what is said.

Revealing and quantifying the impaired phonological analysis underpinning impaired comprehension in Wernicke's aphasia.

Wernicke's aphasia is a condition which results in severely disrupted language comprehension following a lesion to the left temporo-parietal region. A phonological analysis deficit has traditionally been held to be at the root of the comprehension impairment in Wernicke's aphasia, a view consistent with current functional neuroimaging which finds areas in the superior temporal cortex responsive to phonological stimuli. However behavioural evidence to support the link between a phonological analysis deficit and auditory comprehension has not been yet shown. This study extends seminal work by Blumstein, Baker, and Goodglass (1977) to investigate the relationship between acoustic-phonological perception, measured through phonological discrimination, and auditory comprehension in a case series of Wernicke's aphasia participants. A novel adaptive phonological discrimination task was used to obtain reliable thresholds of the phonological perceptual distance required between nonwords before they could be discriminated. Wernicke's aphasia participants showed significantly elevated thresholds compared to age and hearing matched control participants. Acoustic-phonological thresholds correlated strongly with auditory comprehension abilities in Wernicke's aphasia. In contrast, nonverbal semantic skills showed no relationship with auditory comprehension. The results are evaluated in the context of recent neurobiological models of language and suggest that impaired acoustic-phonological perception underlies the comprehension impairment in Wernicke's aphasia and favour models of language which propose a leftward asymmetry in phonological analysis.

Solving the paradox of the equipotential and modular brain: a neurocomputational model of stroke vs. slow-growing glioma.

In acute brain damage (e.g., stroke), patients can be left with specific deficits while other domains are unaffected, consistent with the classical 'modular' view of cortical organization. On this view, relearning of impaired function is limited because the remaining brain regions, tuned to other domains, have minimal capacity to assimilate an alternative activity. A clear paradox arises in low-grade glioma where an even greater amount of cortex may be affected and resected without impairment. Using a neurocomputational model we account for the modular nature of normal function as well as the contrasting types of brain insult through the interaction of three computational principles: patterns of connectivity; experience-dependent plasticity; and the time course of damage. This work provides support for a neo-Lashleyan view of cortical organization.