fMRI Activation Research Articles

Differential neural activity predicts the long-term stability of the effects of positive and negative expectations on pain.

Expectations modulating pain perception is a well-researched phenomenon, but less is known about the persistence of expectation effects over longer time-courses. In this preregistered study, we examined the persistence of positive (placebo) and negative (nocebo) expectation effects over one week and investigated whether neural activity on day 1 (fMRI) can predict the stability of these effects one week later (n = 41). We tested whether expectations were reflected in EEG oscillatory activity at the second measurement. Both positive and negative pain modulation effects persisted over the tested time-period and did not undergo extinction. Expectations of higher compared to lower pain led to larger theta-to-alpha EEG activity. Most interestingly, differential neural activity in fMRI was correlated with persistent expectations. Individual differences in the persistence of positive expectation effects were related to reduced amygdala activity and enhanced activity in the anterior insula and dorsolateral prefrontal cortex (DLPFC) during the first session. In contrast, persistence of negative expectation effects was predicted by enhanced thalamus activity. Our findings indicate relatively stable placebo and nocebo effects over longer time courses, but this persistence is based on different neural areas for positive and negative expectations.

Long-term neuroplasticity in language networks after anterior temporal lobe resection.

Anterior temporal lobe resection (ATLR) is an effective treatment for drug-resistant temporal lobe epilepsy (TLE), although language deficits may occur after both left and right ATLR. Functional reorganization of the language network has been observed in the ipsilateral and contralateral hemispheres within 12 months after ATLR, but little is known of longer-term plasticity effects. Our aim was to examine the plasticity of language functions up to a decade after ATLR, in relation to cognitive profiles. We examined 24 TLE patients (12 left [LTLE]) and 10 controls across four time points: pre-surgery, 4 months, 12 months, and ~9 years post-ATLR. Participants underwent standard neuropsychological assessments (naming, phonemic, and categorical fluency tests) and a verbal fluency functional magnetic resonance imaging (fMRI) task. Using a flexible factorial design, we analyzed longitudinal fMRI activations from 12 months to ~9 years post-ATLR, relative to controls, with separate analyses for people with hippocampal sclerosis (HS). Change in cognitive profiles was correlated with the long-term change in fMRI activations to determine the "efficiency" of reorganized networks. LTLE patients had increased long-term engagement of the left extra-temporal and contralateral temporal regions, with better language performance linked to bilateral activation. Those with HS exhibited more widespread bilateral activations. RTLE patients showed plasticity in the left extra-temporal regions, with better language outcomes associated with these areas. Both groups of patients achieved cognitive stability over 9 years, with more than 50% of LTLE patients improving. Older age, longer epilepsy duration, and lower pre-operative cognitive reserve negatively affected long-term language performance. Neuroplasticity continues for up to ~9 years post-epilepsy surgery in LTLE and RTLE, with effective language recovery linked to bilateral engagement of temporal and extra-temporal regions. This adaptive reorganization is associated with improved cognitive outcomes, challenging the traditional view of localized surgery effects. These findings emphasize the need for early intervention, tailored pre-operative counseling, and the potential for continued cognitive gains with extended post-ATLR rehabilitation.

Resting-state fMRI activation is associated with parent-reported phenotypic features of autism in early adolescence

IntroductionAutism Spectrum Disorder (ASD) is characterized by deficits in social cognition, self-referential processing, and restricted repetitive behaviors. Despite the established clinical symptoms and neurofunctional alterations in ASD, definitive biomarkers for ASD features during neurodevelopment remain unknown. In this study, we aimed to explore if activation in brain regions of the default mode network (DMN), specifically the medial prefrontal cortex (MPC), posterior cingulate cortex (PCC), superior temporal sulcus (STS), inferior frontal gyrus (IFG), angular gyrus (AG), and the temporoparietal junction (TPJ), during resting-state functional magnetic resonance imaging (rs-fMRI) is associated with possible phenotypic features of autism (PPFA) in a large, diverse youth cohort.MethodsWe used cross-sectional parent-reported PPFA data and youth rs-fMRI brain data as part of the two-year follow-up of the Adolescent Brain Cognitive Development (ABCD) study. Our sample consisted of 7,106 (53% male) adolescents aged 10-13. We conducted confirmatory factor analyses (CFAs) to establish the viability of our latent measurements: features of autism and regional brain activation. Structural regression analyses were used to investigate the associations between the six brain regions and the PPFA.ResultsWe found that activation in the MPC (β = .16, p < .05) and the STS (β = .08, p < .05), and being male (β = .13, p < .05), was positively associated with PPFA. In contrast, activation in the IFG (β = −.08, p < .05) was negatively associated.DiscussionOur findings suggest that regions of the “social brain” are associated with PPFA during early adolescence. Future research should characterize the developmental trajectory of social brain regions in relation to features of ASD, specifically brain regions known to mature relatively later during development.

Repetitive Transcranial Magnetic Stimulation on Individualized Spots Based on Task functional Magnetic Resonance Imaging Improves Swallowing Function in Poststroke Dysphagia.

Background: Functional magnetic resonance imaging (fMRI) has not previously been used to localize the swallowing functional area in repetitive transcranial magnetic stimulation (rTMS) treatment for poststroke dysphagia; Traditionally, the target area for rTMS is the hotspot, which is defined as the specific region of the brain identified as the optimal location for transcranial magnetic stimulation (TMS). This study aims to compare the network differences between the TMS hotspot and the saliva swallowing fMRI activation to determine the better rTMS treatment site and investigate changes in functional connectivity related to poststroke dysphagia using resting-state fMRI. Methods: Using an information-based approach, we conducted a single case study to explore neural functional connectivity in a patient with poststroke dysphagia before, immediately after rTMS, and 4 weeks after rTMS intervention. A total of 20 healthy participants underwent fMRI and TMS hotspot localization as a control group. Neural network alterations were assessed, and functional connections related to poststroke dysphagia were examined using resting-state fMRI. Results: Compared to the TMS-induced hotspots, the fMRI activation peaks were located significantly more posteriorly and exhibited stronger functional connectivity with bilateral postcentral gyri. Following rTMS treatment, this patient developed functional connection between the brainstem and the bilateral insula, caudate, anterior cingulate cortex, and cerebellum. Conclusion: The saliva swallowing fMRI activation peaks show more intense functional connectivity with bilateral postcentral gyri compared to the TMS hotspots. Activation peak-guided rTMS treatment improves swallowing function in poststroke dysphagia. This study proposes a novel and potentially more efficacious therapeutic target for rTMS, expanding its therapeutic options for treating poststroke dysphagia.

Inducing representational change in the hippocampus through real-time neurofeedback.

When you perceive or remember something, other related things come to mind, affecting how these competing items are subsequently perceived and remembered. Such behavioural consequences are believed to result from changes in the overlap of neural representations of these items, especially in the hippocampus. According to multiple theories, hippocampal overlap should increase (integration) when there is high coactivation between cortical representations. However, prior studies used indirect proxies for coactivation by manipulating stimulus similarity or task demands. Here, we induce coactivation in visual cortex more directly using closed-loop neurofeedback from real-time functional magnetic resonance imaging (fMRI). While viewing one object, participants were rewarded for activating the representation of another object as strongly as possible. Across multiple real-time fMRI sessions, participants succeeded in using this neurofeedback to increase coactivation. Compared with a baseline of untrained objects, this protocol led to memory integration in behaviour and the brain: the trained objects became harder for participants to discriminate behaviourally in a categorical perception task and harder to discriminate neurally from patterns of fMRI activity in their hippocampus as a result of losing unique features. These findings demonstrate that neurofeedback can be used to alter and combine memories.This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Pain Catastrophizing and Functional Activation During Occlusion in TMD Patients-An Interventional Study.

In temporomandibular disorder (TMD), the effects of standard interventions such as using an occlusal splint and its impact on pain relief and pain catastrophizing are poorly understood. Earlier work pointed to a crucial role of insula activation with changes in pain relief by occlusal splint treatment. We performed a functional imaging study using specially developed splint systems to allow for a placebo-controlled longitudinal design. Using functional MRI we examined 20 TMD patients during repetitive occlusal movements at baseline and over the course of splint therapy and also collected self-reported pain catastrophizing. For balancing performance between baseline and after intervention we used occlusion force measures in an individualized fMRI-splint system. Splint therapy lasted for approximately 7 weeks with one group selected by randomization wearing a palatine placebo splint over the first 3 weeks (delayed start; 11 individuals). As expected, fMRI activation in areas involved in pain processing (insula, primary and secondary somatosensory cortex) decreased with intervention. At baseline a positive correlation between activation of the left anterior insula and pain catastrophizing was present. Both parameters decreased over intervention while associations were primarily observable for patients with rather mild TMD.

Monorhinal and Birhinal Odor Processing in Humans: an fMRI investigation.

The olfactory nerve, also known as cranial nerve I, is known to have exclusive ipsilateral projections to primary olfactory cortical structures. However, the lateralization of olfactory processes is known to depend on the task and nature of stimuli. It still remains unclear whether olfactory system projections in humans also correspond to functional pathways during olfactory tasks without any trigeminal, perceptual or cognitive-motor components. Twenty young healthy subjects with a normal sense of smell took part in an olfactory functional magnetic resonance imaging (fMRI) study. We used two types of nostril specific stimulation, passive (no sniffing) and active (with sniffing), with phenyl ethyl alcohol, a pure olfactory stimulant, to investigate fMRI activity patterns in primary and secondary olfactory-related brain structures. Irrespective of the stimulated nostril and the type of stimulation, we detected symmetrical activity in primary and secondary olfactory-related brain structures such as the primary olfactory cortex, entorhinal cortex, and orbitofrontal cortex. In the absence of perceptual or cognitive-motor task demands, the perception of monorhinally presented pure odors is processed bilaterally in the brain.

The relationship between white matter architecture and language lateralisation in the healthy brain.

Interhemispheric anatomical differences have long been thought to be related to language lateralisation. Previous studies have explored whether asymmetries in the diffusion characteristics of white matter language tracts are consistent with language lateralisation. These studies, typically with smaller cohorts, yielded mixed results. This study investigated whether connectomic analysis of quantitative anisotropy (QA) and shape features of white matter tracts across the whole brain are associated with language lateralisation. We analysed 1040 healthy individuals (562 females) from the Human Connectome Project database. Hemispheric language dominance for each participant was quantified using a laterality quotient (LQ) derived from fMRI activation in regions of interest (ROIs) associated with a language comprehension task compared against a math task. A linear regression model was used to examine the relationship between structural asymmetry and functional lateralisation. Connectometry revealed a significant negative correlation between LQs and QA of corpus callosum tracts, indicating that higher QA in these regions is associated with bilateral and right-hemisphere language representation in frontal and temporal regions, respectively. Left language laterality in temporal lobe was significantly associated with longer right inferior fronto-occipital fasciculus (IFOF) and forceps minor tracts. These results suggest that diffusion measures of microstructural architecture as well as geometrical features of reconstructed white matter tracts play a role in language lateralisation. People with increased dependence on right or both frontal hemispheres for language processing may have more developed commissural fibres, which may support more efficient interhemispheric communication.Significance statement The left cerebral hemisphere is dominant for language functions in most people. In some healthy people, language functions are lateralised to the right hemisphere or distributed across both hemispheres. The anatomy underlying patterns of hemispheric language dominance are not well established. Emerging evidence suggests that white matter connectivity and architecture is an important feature of cortical functional organisation. In this work, we report that people who have language functions distributed across both hemispheres have greater inter-hemispheric connectivity compared to lateralised people. Our findings provide further insights into the anatomical basis of language function and may have wider clinical implications.

A gradual transition toward categorical representations along the visual hierarchy during working memory, but not perception.

The ability to stably maintain visual information over brief delays is central to healthy cognitive functioning, as is the ability to differentiate such internal representations from external inputs. One possible way to achieve both is via multiple concurrent mnemonic representations along the visual hierarchy that differ systematically from the representations of perceptual inputs. To test this possibility, we examine orientation representations along the visual hierarchy during perception and working memory. Human participants directly viewed, or held in mind, oriented grating patterns, and the similarity between fMRI activation patterns for different orientations was calculated throughout retinotopic cortex. During direct viewing of grating stimuli, similarity was relatively evenly distributed amongst all orientations, while during working memory the similarity was higher around oblique orientations. We modeled these differences in representational geometry based on the known distribution of orientation information in the natural world: The "veridical" model uses an efficient coding framework to capture hypothesized representations during visual perception. The "categorical" model assumes that different "psychological distances" between orientations result in orientation categorization relative to cardinal axes. During direct perception, the veridical model explained the data well. During working memory, the categorical model gradually gained explanatory power over the veridical model for increasingly anterior retinotopic regions. Thus, directly viewed images are represented veridically, but once visual information is no longer tethered to the sensory world there is a gradual progression to more categorical mnemonic formats along the visual hierarchy.

Beyond the Spectrum: Subtype-Specific Molecular Insights into Autism Spectrum Disorder Via Multimodal Data Integration.

Some toddlers with autism spectrum disorder (ASD) have mild social symptoms and developmental improvement in skills, but for others, symptoms and abilities are moderately or even severely affected. Those with profound autism have the most severe social, language, and cognitive symptoms and are at the greatest risk of having a poor developmental outcome. The little that is known about the underlying biology of this important profound autism subtype, points clearly to embryonic dysregulation of proliferation, differentiation and neurogenesis. Because it is essential to gain foundational knowledge of the molecular biology associated with profound, moderate, and mild autism clinical subtypes, we used well-validated, data-driven patient subtyping methods to integrate clinical and molecular data at 1 to 3 years of age in a cohort of 363 ASD and controls representative of the general pediatric population in San Diego County. Clinical data were diagnostic, language, cognitive and adaptive ability scores. Molecular measures were 50 MSigDB Hallmark gene pathway activity scores derived from RNAseq gene expression. Subtyping identified four ASD, typical and mixed diagnostic clusters. 93% of subjects in one cluster were profound autism and 93% in a different cluster were control toddlers; a third cluster was 76% moderate ability ASD; and the last cluster was a mix of mild ASD and control toddlers. Among the four clusters, the profound autism subtype had the most severe social symptoms, language, cognitive, adaptive, social attention eye tracking, social fMRI activation, and age-related decline in abilities, while mild autism toddlers mixed within typical and delayed clusters had mild social symptoms, and neurotypical language, cognitive and adaptive scores that improved with age compared with profound and moderate autism toddlers in other clusters. In profound autism, 7 subtype-specific dysregulated gene pathways were found; they control embryonic proliferation, differentiation, neurogenesis, and DNA repair. To find subtype-common dysregulated pathways, we compared all ASD vs TD and found 17 ASD subtype-common dysregulated pathways. These common pathways showed a severity gradient with the greatest dysregulation in profound and least in mild. Collectively, results raise the new hypothesis that the continuum of ASD heterogeneity is moderated by subtype-common pathways and the distinctive nature of profound autism is driven by the differentially added profound subtype-specific embryonic pathways.

Effects of high-definition tDCS targeting individual motor hotspot with EMG-driven robotic hand training on upper extremity motor function: a pilot randomized controlled trial

BackgroundDelivering HD-tDCS on individual motor hotspot with optimal electric fields could overcome challenges of stroke heterogeneity, potentially facilitating neural activation and improving motor function for stroke survivors. However, the intervention effect of this personalized HD-tDCS has not been explored on post-stroke motor recovery. In this study, we aim to evaluate whether targeting individual motor hotspot with HD-tDCS followed by EMG-driven robotic hand training could further facilitate the upper extremity motor function for chronic stroke survivors.MethodsIn this pilot randomized controlled trial, eighteen chronic stroke survivors were randomly allocated into two groups. The HDtDCS-group (n = 8) received personalized HD-tDCS using task-based fMRI to guide the stimulation on individual motor hotspot. The Sham-group (n = 10) received only sham stimulation. Both groups underwent 20 sessions of training, each session began with 20 min of HD-tDCS and was then followed by 60 min of robotic hand training. Clinical scales (Fugl-meyer Upper Extremity scale, FMAUE; Modified Ashworth Scale, MAS), and neuroimaging modalities (fMRI and EEG-EMG) were conducted before, after intervention, and at 6-month follow-up. Two-way repeated measures analysis of variance was used to compare the training effect between HDtDCS- and Sham-group.ResultsHDtDCS-group demonstrated significantly better motor improvement than the Sham-group in terms of greater changes of FMAUE scores (F = 6.5, P = 0.004) and MASf (F = 3.6, P = 0.038) immediately and 6 months after the 20-session intervention. The task-based fMRI activation significantly shifted to the ipsilesional motor area in the HDtDCS-group, and this activation pattern increasingly concentrated on the motor hotspot being stimulated 6 months after training within the HDtDCS-group, whereas the increased activation is not sustainable in the Sham-group. The neuroimaging results indicate that neural plastic changes of the HDtDCS-group were guided specifically and sustained as an add-on effect of the stimulation.ConclusionsStimulating the individual motor hotspot before robotic hand training could further enhance brain activation in motor-related regions that promote better motor recovery for chronic stroke.Trial registrationThis study was retrospectively registered in ClinicalTrials.gov (ID NCT05638464).

The role of variation in phonological and semantic working memory capacities in sentence comprehension: neural evidence from healthy and brain-damaged individuals.

Research on the role of working memory (WM) in language processing has typically focused on WM for phonological information. However, considerable behavioral evidence supports the existence of a separate semantic WM system that plays a greater role in language processing. We review the neural evidence that supports the distinction between phonological and semantic WM capacities and discuss how individual differences in these capacities relate to sentence processing. In terms of neural substrates, findings from multivariate functional MRI for healthy participants and voxel-based lesion-symptom mapping for brain-damaged participants imply that the left supramarginal gyrus supports phonological WM, whereas the left inferior frontal gyrus (LIFG) and angular gyrus support semantic WM. In sentence comprehension, individual variation in semantic but not phonological WM related to performance in resolving semantic information and the LIFG region implicated in semantic WM showed fMRI activation during the resolution of semantic interference. Moreover, variation for brain-damaged participants in the integrity of a fiber tract supporting semantic WM had a greater relation to the processing of complex sentences than did the integrity of fiber tracts supporting phonological WM. Overall, the neural findings provide converging evidence regarding the distinction of these two capacities and the greater contribution of individual differences in semantic than phonological WM capacity to sentence processing.

Operatic voices engage the default mode network in professional opera singers

Extensive research with musicians has shown that instrumental musical training can have a profound impact on how acoustic features are processed in the brain. However, less is known about the influence of singing training on neural activity during voice perception, particularly in response to salient acoustic features, such as the vocal vibrato in operatic singing. To address this gap, the present study employed functional magnetic resonance imaging (fMRI) to measure brain responses in trained opera singers and musically untrained controls listening to recordings of opera singers performing in two distinct styles: a full operatic voice with vibrato, and a straight voice without vibrato. Results indicated that for opera singers, perception of operatic voice led to differential fMRI activations in bilateral auditory cortical regions and the default mode network. In contrast, musically untrained controls exhibited differences only in bilateral auditory cortex. These results suggest that operatic singing training triggers experience-dependent neural changes in the brain that activate self-referential networks, possibly through embodiment of acoustic features associated with one's own singing style.

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.

Quantitative modeling of the emergence of macroscopic grid-like representations.

When subjects navigate through spatial environments, grid cells exhibit firing fields that are arranged in a triangular grid pattern. Direct recordings of grid cells from the human brain are rare. Hence, functional magnetic resonance imaging (fMRI) studies proposed an indirect measure of entorhinal grid-cell activity, quantified as hexadirectional modulation of fMRI activity as a function of the subject's movement direction. However, it remains unclear how the activity of a population of grid cells may exhibit hexadirectional modulation. Here, we use numerical simulations and analytical calculations to suggest that this hexadirectional modulation is best explained by head-direction tuning aligned to the grid axes, whereas it is not clearly supported by a bias of grid cells toward a particular phase offset. Firing-rate adaptation can result in hexadirectional modulation, but the available cellular data is insufficient to clearly support or refute this option. The magnitude of hexadirectional modulation furthermore depends considerably on the subject's navigation pattern, indicating that future fMRI studies could be designed to test which hypothesis most likely accounts for the fMRI measure of grid cells. Our findings also underline the importance of quantifying the properties of human grid cells to further elucidate how hexadirectional modulations of fMRI activity may emerge.

Exaggerated frontoparietal control over cognitive effort-based decision-making in young women with anorexia nervosa.

Effortful tasks are generally experienced as costly, but the value of work varies greatly across individuals and populations. While most mental health conditions are characterized by amotivation and effort avoidance, individuals with anorexia nervosa (AN) persistently engage in effortful behaviors that most people find unrewarding (food restriction, excessive exercise). Current models of AN differentially attribute such extreme weight-control behavior to altered reward responding and exaggerated cognitive control. In a novel test of these theoretical accounts, we employed an established cognitive effort discounting paradigm in combination with fMRI in young acutely underweight female patients with AN (n = 48) and age-matched healthy controls (HC; n = 48). Contrary to the hypothesis that individuals with AN would experience cognitive effort (operationalized as N-back task performance) as less costly than HC participants, groups did not differ in the subjective value (SV) of discounted rewards or in SV-related activation of brain regions involved in reward valuation. Rather, all group differences in both behavior (superior N-back performance in AN and associated effort ratings) and fMRI activation (increased SV-related frontoparietal activation during decision-making in AN even for easier choices) were more indicative of increased control. These findings suggest that while effort discounting may be relatively intact in AN, effort investment is high both when performing demanding tasks and during effort-based decision-making; highlighting cognitive overcontrol as an important therapeutic target. Future research should establish whether exaggerated control during effort-based decision-making persists after weight-recovery and explore learning the value of effort in AN with tasks involving disorder-relevant effort demands and rewards.

A Multimodal Magnetic Resonance Imaging Study on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Feasibility and Clinical Correlation.

Background/Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neurological disorder characterized by post-exertional malaise. Despite its clinical relevance, the disease mechanisms of ME/CFS are not fully understood. The previous studies targeting brain function or metabolites have been inconclusive in understanding ME/CFS complexity. We combined single-voxel magnetic resonance spectroscopy (SV-MRS) and functional magnetic resonance imaging (fMRI). Our objectives were to examine the feasibility of the multimodal MRI protocol, identify possible differences between ME/CFS and healthy controls (HCs), and relate MRI findings with clinical symptoms. Methods: We enrolled 18 female ME/CFS participants (mean age: 39.7 ± 12.0 years) and five HCs (mean age: 45.6 ± 14.5 years). SV-MRS spectra were acquired from three voxels of interest: the anterior cingulate gyrus (ACC), brainstem (BS), and left dorsolateral prefrontal cortex (L-DLPFC). Whole-brain fMRI used n-back task testing working memory and executive function. The feasibility was assessed as protocol completion rate and time. Group differences in brain metabolites and fMRI activation between ME/CFS and HCs were compared and correlated with behavioral and symptom severity measurements. Results: The completion rate was 100% regardless of participant group without causing immediate fatigue. ME/CFS appeared to show a higher N-Acetylaspartate in L-DLPFC compared to HCs (OR = 8.49, p = 0.040), correlating with poorer fatigue, pain, and sleep quality scores (p's = 0.001-0.015). An increase in brain activation involving the frontal lobe and the brainstem was observed in ME/CFS compared to HCs (Z > 3.4, p's < 0.010). Conclusions: The study demonstrates the feasibility of combining MRS and fMRI to capture neurochemical and neurophysiological features of ME/CFS in female participants. Further research with larger cohorts of more representative sampling and follow-ups is needed to validate these apparent differences between ME/CFS and HCs.

Replay-triggered brain-wide activation in humans

The consolidation of discrete experiences into a coherent narrative shapes the cognitive map, providing structured mental representations of our experiences. In this process, past memories are reactivated and replayed in sequence, fostering hippocampal-cortical dialogue. However, brain-wide engagement coinciding with sequential reactivation (or replay) of memories remains largely unexplored. In this study, employing simultaneous EEG-fMRI, we capture both the spatial and temporal dynamics of memory replay. We find that during mental simulation, past memories are replayed in fast sequences as detected via EEG. These transient replay events are associated with heightened fMRI activity in the hippocampus and medial prefrontal cortex. Replay occurrence strengthens functional connectivity between the hippocampus and the default mode network, a set of brain regions key to representing the cognitive map. On the other hand, when subjects are at rest following learning, memory reactivation of task-related items is stronger than that of pre-learning rest, and is also associated with heightened hippocampal activation and augmented hippocampal connectivity to the entorhinal cortex. Together, our findings highlight a distributed, brain-wide engagement associated with transient memory reactivation and its sequential replay.

Reduced expression of fMRI subsequent memory effects with increasing severity across the Alzheimer’s disease risk spectrum

Abstract In functional magnetic resonance imaging (fMRI) studies, episodic memory is commonly investigated with the subsequent memory paradigm in which brain activity is recorded during encoding and analyzed as a function of subsequent remembering and forgetting. Impaired episodic memory is common in individuals with or at risk for Alzheimer’s disease (AD), but only few studies have reported subsequent memory effects in AD or its risk states like mild cognitive impairment (MCI). One reason for this might be that subsequent memory responses may be blunted in AD or MCI and thus less likely to manifest in fMRI signal differences. Here, we used Bayesian model selection of single-subject fMRI general linear models (GLMs) for a visual novelty and memory encoding experiment to compare the model performance of categorical and parametric subsequent memory models as well as memory-invariant models in a clinical cohort (N = 468) comprising healthy controls (HC) as well as individuals with subjective cognitive decline (SCD), MCI, and AD, plus healthy relatives of AD patients (AD-rel). We could replicate the previously reported superiority of parametric subsequent memory models over categorical models (Soch, Richter, Schütze, Kizilirmak, Assmann, Knopf, et al., 2021) in the HC and also in the SCD and AD-rel groups. However, memory-invariant models outperformed any model assuming subsequent memory effects in the MCI and AD groups. In the AD group, we additionally found substantially lower model preference for models assuming novelty compared to models not differentiating between novel and familiar stimuli. Our results suggest that voxel-wise memory-related fMRI activity patterns in AD and also MCI should be interpreted with caution and point to the need for additional or alternative approaches to investigate memory function.

Spatial memory encoding is associated with the anterior and posterior hippocampus: An fMRI activation likelihood estimation meta-analysis.

It has been hypothesized that differential processing occurs along the longitudinal (anterior-posterior) axis of the hippocampus. One hypothesis is that spatial memory (during both encoding and retrieval) is associated with the posterior hippocampus. An alternative hypothesis is that memory encoding (either spatial or nonspatial) is associated with the anterior hippocampus and memory retrieval is associated with the posterior hippocampus. Of importance, during spatial memory encoding, the spatial-posterior hypothesis predicts posterior hippocampal involvement, whereas the encoding-retrieval hypothesis predicts anterior hippocampal involvement. To distinguish between these hypotheses, we conducted a coordinate-based fMRI activation likelihood estimation (ALE) meta-analysis of 26 studies (with a total of 435 participants) that reported hippocampal activity during spatial memory encoding and/or spatial memory retrieval. Both spatial memory encoding and spatial memory retrieval produced extensive activity along the longitudinal axis of the hippocampus as well as the entorhinal cortex, the perirhinal cortex, and the parahippocampal cortex. Critically, the contrast of spatial memory encoding and spatial memory retrieval produced activations in both the anterior hippocampus and the posterior hippocampus. That spatial memory encoding produced activity in both the anterior and posterior hippocampus can be taken to reject strict forms of the spatial-posterior hypothesis, which stipulates that all forms of spatial memory produce activity in the posterior hippocampus, and the encoding-retrieval hypothesis, which stipulates that all forms of encoding versus retrieval produce activity in only the anterior hippocampus. Our results indicate that spatial memory encoding can involve the anterior hippocampus and the posterior hippocampus.