James L. Keidel

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 videos 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. SIGNIFICANCE STATEMENT Memories are strengthened via consolidation. We investigated memory for lifelike events using video clips and showed that rehearsing their content dramatically boosts memory consolidation. Using MRI scanning, we measured patterns of brain activity while watching the videos and showed that, in a network of brain regions, similar patterns of brain activity are reinstated when rehearsing the same videos. Within the posterior cingulate, the strength of reinstatement predicted how well the videos were remembered a week later. The findings extend our knowledge of the brain regions important for creating long-lasting memories for complex, lifelike events.

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.

The anterior temporal lobes support residual comprehension in Wernicke’s aphasia

Robson et al. use fMRI to investigate preserved written word and picture comprehension in Wernicke’s aphasia (impaired verbal comprehension following left temporoparietal damage). Bilaterally enhanced activation in the ventral and anterior temporal lobes as patients semantically process visually presented material emphasizes the importance of these regions for multimodal comprehension.

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

Wernickes 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 Wernickes 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 Wernickes 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. Wernickes aphasia participants showed significantly elevated thresholds compared to age and hearing matched control participants. Acoustic-phonological thresholds correlated strongly with auditory comprehension abilities in Wernickes 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 Wernickes aphasia and favour models of language which propose a leftward asymmetry in phonological analysis.

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 Shakespeares grammatical exploration forces the listener to take a more active role in integrating the meaning of what is said.

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.

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.

Multiscale integration of contextual information during a naturalistic task

Abstract 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.