Spatiotemporal precision of neuroimaging in psychiatry

Aberrant patterns of cognition, perception, and behaviour seen in psychiatric disorders are thought to be driven by a complex interplay of neural processes that evolve at a rapid temporal scale. Understanding these dynamic processes in vivo in humans has been hampered by a trade-off between the spatial and temporal resolution inherent to current neuroimaging technology. A recent trend in psychiatric research has been the use of high temporal resolution imaging, particularly magnetoencephalography (MEG), often in conjunction with sophisticated machine learning decoding techniques. Developments here promise novel insights into the spatiotemporal dynamics of cognitive phenomena, including domains relevant to psychiatric illness such as reward and avoidance learning, memory, and planning. This review considers recent advances afforded by exploiting this increased spatiotemporal precision, with specific reference to applications the seek to drive a mechanistic understanding of psychopathology and the realisation of preclinical translation

Alpha Rhythms Reveal When and Where Item and Associative Memories Are Retrieved

Memories for past experiences can range from vague recognition to full-blown recall of associated details. Electroencephalography has shown that recall signals unfold a few hundred milliseconds after simple recognition, but has only provided limited insights into the underlying brain networks. Functional magnetic resonance imaging (fMRI) has revealed a “core recollection network” (CRN) centered on posterior parietal and medial temporal lobe regions, but the temporal dynamics of these regions during retrieval remain largely unknown. Here we used Magnetoencephalography in a memory paradigm assessing correct rejection (CR) of lures, item recognition (IR) and associative recall (AR) in human participants of both sexes. We found that power decreases in the alpha frequency band (10–12 Hz) systematically track different mnemonic outcomes in both time and space: Over left posterior sensors, alpha power decreased in a stepwise fashion from 500 ms onward, first from CR to IR and then from IR to AR. When projecting alpha power into source space, the CRN known from fMRI studies emerged, including posterior parietal cortex (PPC) and hippocampus. While PPC showed a monotonic change across conditions, hippocampal effects were specific to recall. These region-specific effects were corroborated by a separate fMRI dataset. Importantly, alpha power time courses revealed a temporal dissociation between item and associative memory in hippocampus and PPC, with earlier AR effects in hippocampus. Our data thus link engagement of the CRN to the temporal dynamics of episodic memory and highlight the role of alpha rhythms in revealing when and where different types of memories are retrieved

The spectro-contextual encoding and retrieval theory of episodic memory.

The spectral fingerprint hypothesis, which posits that different frequencies of oscillations underlie different cognitive operations, provides one account for how interactions between brain regions support perceptual and attentive processes (Siegel etal., 2012). Here, we explore and extend this idea to the domain of human episodic memory encoding and retrieval. Incorporating findings from the synaptic to cognitive levels of organization, we argue that spectrally precise cross-frequency coupling and phase-synchronization promote the formation of hippocampal-neocortical cell assemblies that form the basis for episodic memory. We suggest that both cell assembly firing patterns as well as the global pattern of brain oscillatory activity within hippocampal-neocortical networks represents the contents of a particular memory. Drawing upon the ideas of context reinstatement and multiple trace theory, we argue that memory retrieval is driven by internal and/or external factors which recreate these frequency-specific oscillatory patterns which occur during episodic encoding. These ideas are synthesized into a novel model of episodic memory (the spectro-contextual encoding and retrieval theory, or "SCERT") that provides several testable predictions for future research

Alpha Rhythms Reveal When and Where Item and Associative Memories Are Retrieved.

Memories for past experiences can range from vague recognition to full-blown recall of associated details. Electroencephalography has shown that recall signals unfold a few hundred milliseconds after simple recognition, but has only provided limited insights into the underlying brain networks. Functional magnetic resonance imaging (fMRI) has revealed a "core recollection network" (CRN) centered on posterior parietal and medial temporal lobe regions, but the temporal dynamics of these regions during retrieval remain largely unknown. Here we used Magnetoencephalography in a memory paradigm assessing correct rejection (CR) of lures, item recognition (IR) and associative recall (AR) in human participants of both sexes. We found that power decreases in the alpha frequency band (10-12 Hz) systematically track different mnemonic outcomes in both time and space: Over left posterior sensors, alpha power decreased in a stepwise fashion from 500 ms onward, first from CR to IR and then from IR to AR. When projecting alpha power into source space, the CRN known from fMRI studies emerged, including posterior parietal cortex (PPC) and hippocampus. While PPC showed a monotonic change across conditions, hippocampal effects were specific to recall. These region-specific effects were corroborated by a separate fMRI dataset. Importantly, alpha power time courses revealed a temporal dissociation between item and associative memory in hippocampus and PPC, with earlier AR effects in hippocampus. Our data thus link engagement of the CRN to the temporal dynamics of episodic memory and highlight the role of alpha rhythms in revealing when and where different types of memories are retrieved.SIGNIFICANCE STATEMENT Our ability to remember ranges from the vague feeling of familiarity to vivid recollection of associated details. Scientific understanding of episodic memory thus far relied upon separate lines of research focusing on either temporal (via electroencephalography) or spatial (via functional magnetic resonance imaging) dimensions. However, both techniques have limitations that have hindered understanding of when and where memories are retrieved. Capitalizing on the enhanced temporal and spatial resolution of magnetoencephalography, we show that changes in alpha power reveal both when and where different types of memory are retrieved. Having access to the temporal and spatial characteristics of successful retrieval provided new insights into the cross-regional dynamics in the hippocampus and parietal cortex

Electrophysiological signatures of event segmentation during movie viewing and recall

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Sinais e Imagens Médicas) Universidade de Lisboa, Faculdade de Ciências, 2018Perception and memory have been widely studied in the context of discrete pictures or words. However, in real-life, we are faced with a continuous stream of perceptual input that arrive on a wide range of timescales. Previous studies have shown that our brain can segment this continuous stream of information into events that not only reveal a hierarchy from coarse to fine time-scales, but also integrate them differently throughout the cortex, with processing timescales increasing from tens of milliseconds in early sensory regions up to hundreds of seconds in higherorder regions. However, the neural mechanisms that support such event segmentation process during online encoding of a naturalistic and continuous experience remain unknown. To address this issue, we tested whether the formation of meaningful event models could be expressed by specific patterns of electrophysiological activity recorded from healthy humans elicited during the online encoding of a 50 minutes movie and if these patterns were predictive of participant’s later memory recall of the encoded events during a free verbal and unguided recall test. Our results provide the first electrophysiological evidence for a memory related oscillatory signature of the event segmentation process. We found that, when facing a naturalistic continuous stimuli, our brain perceives the information in the form of discrete events which are stored in memory during a process that seems to occur approximately 400 ms after the end of each event and that is indeed predictive of later reinstatement of those events. This neural process suggests a possible congruency/incongruency evaluation mechanism which might represent the errorbased updating mechanism, in which event models are updated at event boundaries in response to transient increases in prediction error, suggested by the Event Segmentation Theory. Our results also prove that naturalistic stimuli can be used in electroencephalography measurements, despite the natural limitations that arise with the use of such stimuli. In doing so we will be able to study, in a more ecological way, the mechanisms of memory formation during event segmentation.As memórias podem ser definidas como representações duradouras de eventos ocorridos no passado que se reflectem em pensamentos, experiências e comportamentos. Conscientemente ou não, elas são influenciadas pelo passado, necessárias para o nosso dia-a-dia e extremamente importantes no planeamento do nosso futuro. O armazenamento de memórias é feito por parte de inúmeras estruturas cerebrais pertencentes ao neocórtex - parte exterior do córtex - e pelo lobo temporal medial, onde podemos encontrar o hipocampo e seus tecidos envolventes. Estas duas regiões encontram-se em constante diálogo enquanto armazenamos e restabelecemos o fluxo de experiências diárias. Com base no estudo de lesões cerebrais nestas regiões, sabe-se hoje em dia que é possível dividir as memórias em diferentes categorias. As duas principais categorias são memória a curto prazo e a longo prazo. A primeira é responsável pelo armazenamento de informação temporariamente e se essa informação deve ou não ser transferida para a memória a longo prazo. Estas últimas são compostas por memórias conscientes e inconscientes, entre elas as memórias semânticas, episódicas e mais particularmente autobiográficas. Inicialmente as memórias são episódicas e armazenadas no hipocampo e com o tempo são transformadas em memórias semânticas no neocórtex. Recentemente, uma nova linha de investigação tem se focado não na distribuição espacial do processo de armazenamento de memórias mas sim nas suas propriedades temporais e capacidade de distinguir informação que nos é apresentada com diferentes escalas temporais. Por exemplo, quando falamos ou lemos um texto, somos obrigados a identificar as diferentes sílabas para conseguir formar uma palavra, a perceber o sentido dessa palavra no contexto de uma frase, e uma frase no contexto de uma conversa. Não só temos a capacidade de segmentar a informação que percepcionamos mas também de nos lembrarmos desta informação na forma de episódios representativos das nossas experiências prévias. A primeira teoria formulada sobre este processo de segmentação toma o nome de Event Segmentation Theory. Nela a informação processada pelo nosso cérebro é representada por uma série de modelos de eventos, implementados durante rápidas alterações neuronais que ocorrem devido a um mecanismo de avaliação de predição do que deverá acontecer no seguimento de certa experiência. Esta alteração no erro de predição leva à segmentação da informação em diferentes eventos durante momentos a que se dá o nome de fronteiras. Desde a formulação desta teoria inúmeros estudos foram desenvolvidos com o intuito de compreender o funcionamento deste processo de segmentação. Estes estudos permitiramnos obter provas de que a nossa actividade neuronal tem a capacidade de processar informação em diferentes escalas temporais, em diferentes regiões do cérebro. Zonas de processamento sensorial segmentam informação em eventos mais curtos, uma vez que os estímulos sensoriais são geralmente muito rápidos, e zonas de processamento elevado segmentam informação em eventos mais longos uma vez que têm de processar informação perceptual e cognitiva. No entanto, apenas recentemente começaram a surgir estudos que ligam este processo de segmentação à formação de memórias a longo prazo. Uma nova teoria, Theory of Event Segmentation and Memory, proposta o ano passado sugere que cada região cerebral processa informação na sua escala temporal preferida e que estes segmentos de informação são transmitidos de regiões que processam informação a escalas temporais longas para o hipocampo, minutos após ser formada uma fronteira entre dois eventos. Ao ser activado, o hipocampo processa a informação do evento acabado de percepcionar e armazena a informação para que esta possa ser mais tarde reativada nas mesmas regiões de escala temporal longa. Após a formalização desta teoria uma série de outros estudos têm sugerido como principal responsável para a integração da informação de um evento na memória, a resposta neuronal que parece ocorrer durante as fronteiras entre eventos. No entanto, os mecanismos neuronais que suportam esta segmentação e integração na memória durante o processamento de experiências naturais e contínuas continuam por explicar. Com o objetivo de explorar estes mecanismos, neste projeto testámos a possibilidade de a formação de modelos de eventos ser expressa por padrões eletrofisiológicos particulares a este processo. Para tal adquirimos dados de electroencefalograma (EEG) de 30 participantes saudáveis enquanto estes visualizavam 50 min de um filme. Para testar se o aparecimento de padrões neuronais específicos poderia ser preditivo de um correcto processo de memória pedimos aos participantes para, após a visualização do filme, relatar o que tinham acabado de ver de forma livre, mantendo a ordem em que a informação foi apresentada no filme e por quanto tempo conseguissem. Os dados adquiridos foram pré-processados de forma a eliminar a maior quantidade de ruído possível e um modelo com a possível segmentação do filme em diferentes cenas foi construído com base em anotações de seis participantes externos. Após verificar que o sinal adquirido podia ser dividido nos eventos compostos pelo modelo construído este foi utilizado na primeira parte da análise em que o objectivo era avaliar o que se passava no interior dos eventos. Para tal os padrões neuronais adquiridos tanto durante a visualização do filme como durante o relato do mesmo foram comparados entre si para cada participante e comparados entre participantes. Verificámos que os padrões neuronais eram semelhantes entre participantes tanto para os dados obtidos durante a visualização do filme, em que o estímulo é o mesmo para todos os participantes, como para os dados adquiridos durante o relato, em que os participantes descrevem o filme de forma diferente. Apenas obtivemos elevados valores de semelhança entre os padrões do filme e o relato quando recorremos a um algoritmo de segmentação baseado em Hidden Markov Models para que a segmentação dos dados do relato fosse feita de forma individual para cada participante. Estes resultados permitem-nos concluir que o processo de armazenamento e restabelecimento de memórias é feito de forma semelhante e com base em eventos. Correlações entre diferentes propriedades dos eventos (duração do evento, ordenação dos eventos durante o relato, detalhes relatados em cada evento e autocorrelação do padrão neuronal de cada evento) e a precisão com o que filme é relatado para cada participante foram calculadas de forma a perceber se alguma destas propriedades poderia prever se um evento seria mais tarde relembrado durante o relato ou não. Apenas a duração do evento mostrou ser significativa o que indica que os processos que se desenvolvem durante a visualização de um evento não parecem ser decisivos para a sua integração na memória. Após estudar o que se passava no interior de cada evento a nossa atenção voltou-se para as fronteiras entre eventos. Para tal começámos por realizar uma análise de similaridade espaçotemporal (STPS) em que comparámos os padrões neuronais 5 s após as fronteiras com os 5 s antes das fronteiras e observámos que de facto existe uma alteração nos padrões neuronais quando uma fronteira ocorre, e que esta alteração não pode simplesmente ser explicada por uma distância temporal entre os dois eventos. Para observarmos então com mais distinção a resposta neuronal durante a fronteira, calculámos os event related potentials (ERPs), 2 s após cada fronteira, para todas as fronteiras e todos os participantes. Nestes, encontrámos uma clara distinção entre fronteiras correspondentes a eventos que não foram e que foram mais tarde relatados. A resposta neuronal dos eventos mais tarde relembrados está marcada pelo aparecimento do componente N400, conhecido por aparecer quando ocorre uma incongruência na informação a ser percepcionada. Estes resultados sugerem que, quando uma fronteira ocorre dá-se uma avaliação de congruência com a informação do evento passado e, quando mais incongruente for esta informação, melhor será armazenada na memória e mais tarde relembrada. Este mecanismo está de acordo com o mecanismo de avaliação de previsão proposto pela Event Segmentation Theory. Em suma os nossos resultados demonstram a existência de um padrão neuronal característico do processo de segmentação com aparecimento aproximadamente 400 ms após a formação de uma fronteira entre eventos, crucial para a correta integração desse evento na memória. Os nossos resultados provam também a validade de utilização de um estímulo naturalístico em estudos de segmentação de memória que utilizam medições electrofisiológicas. Este estudo abre portas para investigações futuras em que será essencial determinar como ocorre a distribuição espacial deste padrão neuronal, aqui apenas sugerida devido à baixa resolução espacial do EEG, e validar a existência deste padrão em estudos cada vez mais naturalísticos, com recurso por exemplo a medições por electrocorticografia (ECoG)

Brain network analyses in clinical neuroscience

Network analyses are now considered fundamental for understanding brain function. Nonetheless neuroimaging characterisations of connectivity are just emerging in clinical neuroscience. Here, we briefly outline the concepts underlying structural, functional and effective connectivity, and discuss some cutting-edge approaches to the quantitative assessment of brain architecture and dynamics. As illustrated by recent evidence, comprehensive and integrative network analyses offer the potential for refining pathophysiological concepts and therapeutic strategies in neurological and psychiatric conditions across the lifespan

Spatiotemporal pattern of brain electrical activity related to immediate and delayed episodic memory retrieval

In the present study we used the event-related brain potentials (ERP) technique and eLORETA (exact low-resolution electromagnetic tomography) method in order to characterize and compare the performance and the spatiotemporal pattern of the brain electrical activity related to the immediate episodic retrieval of information (words) that is being learned relative to delayed episodic retrieval twenty-minutes later. For this purpose, 16 young participants carried out an old/new word recognition task with source memory (word colour). The task included an immediate memory phase (with three study-test blocks) followed (20 min later) by a delayed memory phase with one test block. The behavioural data showed progressive learning and consolidation of the information (old words) during the immediate memory phase. The ERP data to correctly identified old words for which the colour was subsequently recollected (H/H) compared to the correctly rejected new words (CR) showed: (1) a significant more positive-going potential in the 500–675 ms post-stimulus interval (parietal old/new effect, related to recollection), and (2) a more negative-going potential in the 950–1850 ms interval (LPN effect, related to retrieval and post-retrieval processes). The eLORETA data also revealed that the successful recognition of old words (and probably retrieval of their colour) was accompanied by activation of (1) left medial temporal (parahippocampal gyrus) and parietal regions involved in the recollection in both memory phases, and (2) prefrontal regions and the superior temporal gyrus (in the immediate and delayed memory phases respectively) involved in monitoring, evaluating and maintaining the retrieval products. These findings indicate that episodic memory retrieval depends on a network involving medial temporal lobe and frontal, parietal and temporal neocortical structures. That network was involved in immediate and delayed memory retrieval and during the course of memory consolidation, with greater activation of some nodes (mobilization of more processing resources) for the delayed respect to the immediate retrieval conditionThis study was supported by grants from the Spanish Government, Ministerio de Ciencia e Innovación (PSI2014-55316-C3-3-R; PSI2017-89389-C2-2-R), with FEDER Funds; the Galician Government, Consellería de Cultura, Educación e Ordenación Universitaria, Axudas para a Consolidación e Estruturación de Unidades de Investigación Competitivas do Sistema Universitario de Galicia: GRC (GI-1807-USC); Ref: ED431-2017/27, with FEDER fundsS

Unintentional and intentional recognition rely on dissociable neurocognitive mechanisms

Distractibility can lead to accidents and academic failures, as well as memory problems. Recent evidence suggests that intentional recognition memory can be biased by unintentional recognition of distracting stimuli in the same environment. It is unknown whether unintentional and intentional recognition depend on the same underlying neurocognitive mechanisms. We assessed whether human participants’ recognition of previously seen (old) or not seen (new) target stimuli was affected by whether a to-be-ignored distractor was old or new. ERPs were recorded to investigate the neural correlates of this bias. The results showed that the old/new status of salient distractors had a biasing effect on target recognition accuracy. Both intentional and unintentional recognition elicited early ERP effects that are thought to reflect relatively automatic memory processes. However, only intentional recognition elicited the later ERP marker of conscious recollection, consistent with previous suggestions that recollection is under voluntary control. In contrast, unintentional recognition was associated with an enhanced late posterior negativity, which may reflect monitoring or evaluation of memory signals. The findings suggest that unintentional and intentional recognition involve dissociable memory processes

Bipartite Functional Fractionation within the Default Network Supports Disparate Forms of Internally Oriented Cognition.

Our understanding about the functionality of the brain's default network (DN) has significantly evolved over the past decade. Whereas traditional views define this network based on its suspension/disengagement during task-oriented behavior, contemporary accounts have characterized various situations wherein the DN actively contributes to task performance. However, it is unclear how different task-contexts drive componential regions of the DN to coalesce into a unitary network and fractionate into different subnetworks. Here we report a compendium of evidence that provides answers to these questions. Across multiple analyses, we found a striking dyadic structure within the DN in terms of the profiles of task-triggered fMRI response and effective connectivity, significantly extending beyond previous inferences based on meta-analysis and resting-state activities. In this dichotomy, one subset of DN regions prefers mental activities "interfacing with" perceptible events, while the other subset prefers activities "detached from" perceptible events. While both show a common "aversion" to sensory-motoric activities, their differential preferences manifest a subdivision that sheds light upon the taxonomy of the brain's memory systems. This dichotomy is consistent with proposals of a macroscale gradational structure spanning across the cerebrum. This gradient increases its representational complexity, from primitive sensory-motoric processing, through lexical-semantic representations, to elaborated self-generated thoughts.This research was funded by an MRC programme grant to MALR (MR/R023883/1) and a Sir Henry Wellcome Fellowship (201381/Z/16/Z) to RC

On the sensitivity of event-related fields to recollection and familiarity

The sensitivity of event-related potentials (ERPs) to the processes of recollection and familiarity has been explored extensively, and ERPs have been used subsequently to infer the contributions these processes make to memory judgments under a range of different circumstances. It has also been shown that event-related fields (ERFs, the magnetic counterparts of ERPs) are sensitive to memory retrieval processes. The links between ERFs, recollection and familiarity are, however, established only weakly. In this experiment, the sensitivity of ERFs to these processes was investigated in a paradigm used previously with ERPs. An early frontally distributed modulation varied with memory confidence in a way that aligns it with the process of familiarity, while a later parietally distributed modulation tracked subjective claims of recollection in a way that aligns it with this process. These data points strengthen the argument for employing ERFs to assess the contributions these processes can make to memory judgments, as well as for investigating the nature of the processes themselves