A study on the specificity of the association between hippocampal volume and delayed primacy performance in cognitively intact elderly individuals.

Delayed recall at the primacy position (first few items on a list) has been shown to predict cognitive decline in cognitively intact elderly participants, with poorer delayed primacy performance associated with more pronounced generalized cognitive decline during follow-up. We have previously suggested that this association is due to delayed primacy performance indexing memory consolidation, which in turn is thought to depend upon hippocampal function. Here, we test the hypothesis that hippocampal size is associated with delayed primacy performance in cognitively intact elderly individuals. Data were analyzed from a group (N=81) of cognitively intact participants, aged 60 or above. Serial position performance was measured with the Buschke selective reminding test (BSRT). Hippocampal size was automatically measured via MRI, and unbiased voxel-based analyses were also conducted to explore further regional specificity of memory performance. We conducted regression analyses of hippocampus volumes on serial position performance; other predictors included age, family history of Alzheimer's disease (AD), APOE ε4 status, education, and total intracranial volume. Our results collectively suggest that there is a preferential association between hippocampal volume and delayed primacy performance. These findings are consistent with the hypothesis that delayed primacy consolidation is associated with hippocampal size, and shed light on the relationship between delayed primacy performance and generalized cognitive decline in cognitively intact individuals, suggesting that delayed primacy consolidation may serve as a sensitive marker of hippocampal health in these individuals

Dynamic changes in prefrontal cortex involvement during verbal episodic memory formation

During encoding, the neural activity immediately before or during an event can predict whether that event will be later remembered. The contribution of brain activity immediately after an event to memory formation is however less known. Here, we used repetitive Transcranial Magnetic Stimulation (rTMS) to investigate the temporal dynamics of episodic memory encoding with a focus on post-stimulus time intervals. At encoding, rTMS was applied during the online processing of the word, at its offset, or 100, 200, 300 or 400 ms thereafter. rTMS was delivered to the left ventrolateral (VLPFC) or dorsolateral prefrontal cortex (DLPFC). VLPFC rTMS during the first few hundreds of milliseconds after word offset disrupted subsequent recognition accuracy. We did not observe effects of DLPFC rTMS at any time point. These results suggest that encoding-related VLPFC engagement starts at a relatively late processing stage, and may reflect brain processes related to the offset of the stimulus

Die neuronalen Korrelate des Primacy-Effekts

Der Primacy-Effekt beschreibt die Tatsache, dass bei einer Präsentation von mehreren Items das erste Item besser wiedererkannt wird als die folgenden. Klassischerweise tritt der Effekt bei der Wiedererkennung von Worten aus langen Wortlisten auf. Aktuelle Studien zeigen beim Einsatz von artikulatorischer Suppression einen Primacy-ähnlichen Effekt auch im Kurzzeitgedächtnis. Bemerkenswerterweise tritt der Effekt nicht beim Rehearsal, also dem ständigen innerlichen Wiederholen der Items auf. Die vorliegende Studie nutzt die funktionelle Kernspintomographie (fMRT), um die neuronalen Korrelate des Primacy-Effekts zu lokalisieren. Hierzu wurde aufbauend auf einem vorangegangenen fMRT-Experiment (Gruber, 2001), welches bei der Wiedererkennung von vorgegebenen Buchstaben unter artikulatorischer Suppression einen Primacy-Effekt zeigte, ein auf fMRT-Bedingungen ausgelegtes experimentelles Design gewählt, welches die statistische Trennung zwischen Encoding-, Maintenance- und Recognitionsphase ermöglichte. Zur Validierung des experimentellen Designs wurde ein Verhaltensexperiment durchgeführt, welches ebenfalls einen Primacy-Effekt unter artikulatorischer Suppression zeigte. Daraufhin wurde das fMRT-Experiment mit insgesamt 12 Probanden durchgeführt. Die Ergebnisse offenbarten, wie auch schon in den Vorexperimenten zu sehen, in den Verhaltensdaten einen signifikanten Primacy-Effekt, in den fMRT-Daten Aktivierungen im linkshemisphärischen prämoto-parietalen Areal unter Rehearsal-Bedingungen sowie bilaterale präfronto-parietale Aktivierungen unter artikulatorischer Suppression. Die Konnektivitätsanalyse ergab eine Interaktion zwischen dem rechten frontalen Operculum und dem bilateralen Hippocampus, welche vermuten lässt, dass der erste Buchstabe in das Langzeitgedächtnis übernommen wurde und daher besser wiedererkannt wird als die folgenden Buchstaben.The „Primacy-Effect“ describes the phenomenon that items at the first position in a word list are significantly easier to memorize than items at positions in the middle. Classically, that effect occurs when a long word list has to be recalled. Current studies showed a similar effect by using the short-term memory under articulatory suppression. Remarkably, that effect did not occur under articulatory rehearsal, which means the permanent recapitulation of the presented items. The present study used functional magnetic resonance imaging (fMRI) to localize the neural correlates of the Primacy-Effect. Based on a previous study (Gruber, 2001), which showed a Primacy-Effect under articulatory suppression, we created an experimental design, which enabled us to separate the different phases (encoding phase, maintenance phase, recognition phase) statisticly. As expected, the result showed the typical activation under articulatory rehearsal and suppression. Furthermore, comparing the recognition of the first item versus the recognition of items in the middle, we found the right frontal operculum being stronger coupled with the bilateral hippocampus in the first case. These results showed a clear Primacy-Effect in the working memory, and we suppose that this can be explained by the transition of the first item into the long-term memory

Serial Position Effect Profiles and Their Neuroanatomical Correlates: Predictors of Conversion to Alzheimer\u27s Disease

The current study was designed to determine whether targeted, premorbid, neuropsychological measures of the serial position effect (SPE) can detect and explain risk for later development of Alzheimer’s disease (AD). The study tested the utility of SPE measures in healthy controls (HC) and individuals already diagnosed with mild cognitive impairment (MCI) or AD. Aim 1 was to determine whether these sensitive, valid neuropsychological measures can explain disease risk. SPE of list-learning are highly sensitive cognitive markers that capture important elements of both linguistic and amnestic mechanisms of encoding, learning, and retrieval. Using the Rey Auditory Verbal Learning Test (RAVLT), we tested two measures of serial position effect scores (SPE-Index) calculated as accuracy recall at different serial positions at Learning, Short-Delay or Long-Delay, as well as SPE profile scores (SPE-Contrast), which compared accuracy recall of two SPE positions. The three SPE-contrast scores were calculated from primacy, middle, and recency list regions at Learning (Learning), short and long delay recall (SD, LD) trials as follows: (1) J-Shape captures difference between recency and primacy scores at Learning (RecencyLearning - PrimacyLearning); (2) Recency-Drop captures change of recency scores from Learning to SD (RecencyLearning – RecencySD); and (3) Primacy Progression captures how primacy accuracy progresses from Learning to LD (PrimacyLD -PrimacyLearning). We first entered both measures to explain risk of conversion to disease status from a) HC (N = 200) to MCI or AD; and b) from MCI (N = 353) to AD using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. We then contrasted the SPE-Index and SPE-Contrast scores to traditional total list-learning scores from the RAVLT as predictors of conversion. In Aim 2 we performed whole-brain analyses and posited that performance of SPE-Index scores would be subserved by distinct brain regions relevant to learning and encoding. We hypothesized that relevant language and memory driven SPE scores would be associated with corresponding neuroanatomical correlates. For example, we predicted that SPE-Primacy scores would be positively correlated with hippocampal, medial temporal, and frontal lobe regions given their associations with semantic encoding and retrieval. Alternately, we hypothesized that SPE-Recency scores would be positively correlated with inferior parietal and superior temporal gyrus regions, which would explain preserved phonological processing of items. Findings supported our Aim 1 hypothesis. We demonstrated that in preclinical (HC) individuals, diminished Short Delay recall performance of a word-list task best explained conversion risk. The Primacy item recall at Short Delay emerged as a particularly sensitive predictor of progression along the clinical AD spectrum for preclinical individuals. Total-RAVLT list scores at Short Delay also emerged as a predictor, although subsequent analyses highlighted that the primacy items at Short Delay were driving this signal. To our knowledge, these data are the first to support the importance of short delay primacy items as a predictor of disease development in the preclinical population. In MCI, all SPE-Contrast profiles in addition to all SPE-Index scores, with the exception of Recency at SD, significantly explained risk of progression to AD. In MCI, the SPE scores’ utility was similar to that of Total-RAVLT list scores. Findings for Aim 2 were mixed. Contrary to our hypotheses, in HC, we found Recency at Long Delay to be associated with left medial orbitofrontal cortical thickness, but no other significant SPE-Index or Total-RAVLT list score to have significant cortical volume or thickness correlates. By the MCI stage, the SPE-Index measures of Primacy and Middle list positions were associated with a range of regional volumes and thicknesses as were Total-RAVLT scores. The SPE-Index scores at this stage of disease did associate with more specific regions than Total-Scores; but SD, which was of primary interest in preclinical individuals, did not emerge with any significant SPE-Index correlates. Together, this study demonstrated that well-selected, theoretically driven neuropsychological measures can play a prominent role in identifying healthy individuals at great risk of developing AD. Importantly, the initial primacy items of long word-lists rely on semantic processing to be encoded. We propose that future study of other biomarkers to associate with SPE-Primacy in healthy individuals will be critical in order to capitalize on its sensitivity as a predictor of future disease. Furthermore, these SPE scores have the benefit of drawing on theoretical underpinnings and mapping on to specific AD disease processes that may be missed by total scores

Input and output order of recall as early markers of cognitive decline

This thesis explored the effects of age on free recall patterns in episodic memory. Neuropsychological and neuroimaging instruments were used to investigate the input (i.e., serial position effects) and output (i.e., temporal vs. spatial contiguity) of free recall in younger vs. healthy older individuals and in older adults with cognitive decline. In study 1 (Chapter 4), primacy (intended as the tendency to better remember items presented at the beginning of a list compared to the middle) at delayed recall was the most accurate serial position effect in predicting conversion to early stage Mild Cognitive Impairment (MCI), from a baseline of cognitively functioning older adults. In study 2 (Chapter 5), age differences in the use of spatial vs. temporal contiguity (intended as the tendency to retrieve items following the temporal, or spatial, context in which they have been learned) were explored in younger vs. healthy older adults. It was found that temporal contiguity was the most utilised associative process in both groups, although older adults showed lower temporal contiguity compared to younger adults. In study 3 (Chapter 6), the universality of temporal contiguity and the relationship between attentional processes and the output order of free recall were examined. Temporal vs. spatial contiguity were investigated during tasks meant to interfere with encoding processes, that is Divided Attention (DA) tasks and tasks involving presentation of verbal vs. pictorial material. Results showed consistent use of temporal contiguity in all experimental conditions, therefore suggesting the ubiquity of temporal contiguity and its involvement in retrieval processes. In study 4 (Chapter 7), the output order in free recall was investigated in younger and older adults in relation to prefrontal blood oxygenation, by means of functional Near-Infrared Spectroscopy (fNIRS). It was found that areas involved during temporal contiguity change with age, as younger adults showed greater activity of the right prefrontal cortex, whilst older adults engaged alternative or opposite regions. In study 5 (Chapter 8) the use of unrelated memory lists was investigated as a sensitive measure to detect age-related differences on the use of temporal vs. spatial contiguity. Moreover, age-associated differences in the use of temporal contiguity were explored at immediate vs. delayed recall. It was found that unrelated lists are able to detect age-related changes in the use of contiguity effects, and that temporal contiguity is negatively affected in both younger and older adults at delayed recall. In study 6 (Chapter 9) temporal clustering was investigated as potential predictor of conversion to Cognitive Unimpaired Declining (CUD) status, from a baseline of cognitively functioning older individuals. Results supported the hypothesis that temporal contiguity is a marker of cognitive decline, also when controlling for genetic information and for variables typically used in clinical practice. In summary, the findings of this thesis show that the input and output order of free recall, although quite stable, decline with age and that they may be added as a potential tool for early detection in clinical settings, and in the research field

NIBS as a research tool in studying and enhancing episodic memory in the left prefrontal cortex

In the absence of effective treatments for memory disorders including dementia, NIBS methods are being tested for studying and enhancing memory. Anodal transcranial direct-current stimulation (atDCS) is a safe, non-invasive method of stimulating the brain and modulating neural activity through electrodes placed on the scalp. Controversy has surrounded the implementation of atDCS as a research and clinical tool because of inconsistency in effects and a limited understanding of atDCS parameters and mechanisms. Heterogeneity in atDCS parameters across studies could contribute to the inconsistency in effects. Thus, the current research included a systematic ethodological investigation of atDCS as a potential research and clinical tool. Two meta-analyses and a set of five methodological experiments analysed the efficacy of atDCS given a consistent set of parameters. In younger adults, atDCS led to a weak and volatile effect under certain conditions that fluctuated with modifications to verbal stimuli and sample size. While there was a robust improvement in memory following atDCS over the left PFC in Experiment 1, this effect did not remain consistent in direct and conceptual replications. The metaanalyses provided support to this investigation by demonstrating that when effect sizes were pooled together across all eligible published studies, the average effect size was close to zero. When only the studies in the current investigation were pooled together, the effect size was larger but also non-significant. Thus, the results inform future considerations of atDCS as a research and clinical tool and provide recommendations for the limited applications of atDCS with a framework for applying effective parameters that take into account individual differences. Furthermore, through the course of the investigation of atDCS, novel findings about episodic memory processes and neural correlates were revealed, confirming the importance of activity in the ventrolateral prefrontal cortex (VLPFC) to episodic memory formation. These findings on VLPFC function were further extended with an investigation of the cognitive mechanisms of atDCS effects on VLPFC 3 function in Chapter 6 and an examination of the time window and process in the VLPFC that was most crucial to memory formation with repetitive transcranial magnetic stimulation (rTMS) in Chapter 7. Together, the findings contributed to developing a clearer understanding of atDCS effects on episodic memory and the episodic processes that occur in the VLPFC. This understanding can inform future research in NIBS with other cognitive functions and the development of memory nterventions that can target the VLPFC

Lauletun musiikin vaikutus AVH:n jälkeiseen kielelliseen muistiin sekä pitkäaikaiseen AVH:sta toipumiseen

The prevalence of stroke increases in the ageing population entailing an enormous economic and societal burden. This has raised the need for motivating, effective and easily applicable rehabilitation tools to enhance recovery and neuroplasticity. Music is an important source of enjoyment and well-being across life and it provides a multidomain stimulus that is both pleasant and rewarding, and engages the brain extensively. Previous evidence suggests that daily music listening can enhance cognitive recovery and mood and induce functional and structural neuroplasticity changes after stroke. Songs may also function as a verbal learning aid in healthy subjects. The aim of this thesis was to further explore the specific role of vocal (sung) music as a tool to aid verbal learning and long-term recovery after stroke. In Studies I and II, stroke patients (N = 31) performed a verbal learning task where novel narrative stories were presented in both spoken and sung formats, and underwent MRI at acute and 6-month post-stroke stages. Study I showed that stroke patients, especially those with mild aphasia, learned and recalled the stories better when they were presented in sung than spoken format at the 6-month stage. Exploring the cognitive and neural mechanisms underlying this effect, Study II further showed that non-aphasic patients exhibited more stable recall, indicated by reduced serial position effects, whereas aphasic patients showed a larger recency effect and enhanced chunking in the sung than spoken task. Diffusion tensor imaging and voxel-based morphometry results indicated that these effects were coupled with greater volume of the left arcuate fasciculus in non-aphasics, and with greater volume of the right inferior fronto-occipital fasciculus and grey matter in a bilateral network of temporal, frontal, and parietal regions in aphasics. In Study III, data was pooled from two randomized controlled trials where stroke patients (N = 83) received an intervention involving daily listening to self-selected vocal music, instrumental music, or audiobooks during the first three months after stroke. The recovery was assessed with neuropsychological tests and a mood questionnaire at acute, 3-month and 6-month stages, and structural MRI and functional MRI (fMRI) at acute and 6-month stages. Compared to audiobooks, listening to music enhanced the recovery of language skills and verbal memory and reduced negative mood. Vocal music had the strongest rehabilitative effect on both language and verbal memory, and the positive effects of music listening on language recovery were seen especially in patients with aphasia. Results from voxel-based morphometry and resting-state, and task-based fMRI analyses showed that vocal music listening selectively increased grey matter volume in left temporal areas and functional connectivity in the default mode network from acute to 6-month stage. The findings of the present thesis provide further evidence that listening to vocal music is a useful tool to support cognitive and emotional recovery after stroke and to enhance early language recovery in aphasia. The rehabilitative effects are driven by both structural and functional plasticity changes in temporoparietal networks, which are crucial for emotional processing, language and memory.Väestön ikääntyessä yhä useampi sairastuu aivoverenkiertohäiriöön (AVH), minkä aiheuttama yksilöllinen ja yhteiskunnallinen haitta on valtava. Tästä johtuen tarvitaan motivoivia, tehokkaita ja helposti saatavilla olevia työkaluja tehostamaan kuntoutusta ja edesauttamaan aivojen muovautuvuutta toipumisvaiheessa. Musiikki on tärkeä nautinnon ja hyvinvoinnin lähde ja monipuolinen virike, joka miellyttää, palkitsee ja aktivoi aivoja laajalti. Aiemmissa tutkimuksissa on havaittu, että päivittäinen musiikin kuuntelu AVH:n jälkeisten kuukausien aikana tehostaa kognitiivisten toimintojen ja mielialan kuntoutumista ja saa aikaan toiminnallista ja rakenteellista muovautuvuutta otsa- ja ohimolohkoalueilla sekä limbisillä alueilla, ja että laulut toimivat kielellisen oppimisen tukena terveillä henkilöillä. Tässä väitöskirjassa tarkastellaan erityisesti lauletun musiikin vaikutusta kielelliseen oppimiseen sekä pitkäkestoiseen toipumiseen AVH:n jälkeen. Tutkimuksissa I ja II AVH-potilaille (N = 31) tehtiin kielellinen oppimistehtävä, jossa heille esitettiin uusia tarinoita sekä laulettuna että puhuttuna, ja aivojen rakenteellinen magneettikuvaus (MRI) akuuttivaiheessa ja 6 kk sairastumisen jälkeen. Tutkimus I osoitti, että erityisesti ne potilaat, joilla oli lievä afasia, oppivat ja muistivat toipumisvaiheessa 6 kk sairastumisen jälkeen laulettuna esitetyn tarinan paremmin verrattuna puhuttuna esitettyyn. Tutkimus II selvitti tämän taustalla olevia kognitiivisia ja neuraalisia mekanismeja ja osoitti, että ei-afaattiset potilaat muistivat lauletun tarinan puhuttua tasaisemmin, mikä näkyi pienentyneenä sarjapositiovaikutuksena, kun taas afasiapotilailla lauletun tarinan muistamisessa ilmeni suurempi äskeisyysvaikutus ja tehokkaampi mieltämisyksiköiden muodostaminen (engl. chunking). Diffuusiotensorikuvantamisella ja vokselipohjaisella morfometrialla (VBM) saadut tulokset osoittivat, että nämä efektit olivat yhteydessä vasemman arcuate fasciculus (AF) –radaston tilavuuteen ei-afasiapotilailla ja oikean inferior fronto-occipital fasciculus (IFOF) –radaston sekä bilateraalisten ohimo-, otsa- ja päälakilohkoalueiden tilavuuteen afasiapotilailla. Tutkimuksessa III yhdistettiin kahden satunnaistetun kontrolloidun tutkimuksen AVH-potilaiden aineistot (N = 83) ja tutkittiin, miten kahden kuukauden ajan tapahtuva päivittäinen laulumusiikin, instrumentaalimusiikin tai äänikirjojen kuuntelu vaikuttaa toipumiseen. Toipumista arvioitiin neuropsykologisella tutkimuksella, mielialakyselyllä ja aivojen rakenteellisella ja toiminnallisella MRI (fMRI) -tutkimuksella akuuttivaiheesta aina 6 kk:n vaiheeseen. Äänikirjoihin verrattuna musiikin kuuntelu edisti puhetoimintojen ja kielellisen muistin kuntoutumista sekä vähensi negatiivista mielialaa. Laulumusiikilla oli voimakkain vaikutus sekä puheen että muistin kuntoutumiseen etenkin afasiapotilailla. VBM- ja fMRI-tulokset osoittivat, että laulumusiikin kuuntelu lisäsi harmaan aineen tilavuutta vasemmalla ohimolohkolla ja toiminnallista konnektiivisuutta oletustilaverkostossa 6 kk aikana. Tämän väitöskirjan tulokset tuovat lisää näyttöä päivittäisen musiikin kuuntelun positiivisesta vaikutuksesta ja tukevat sen käyttöä toimivana, helppona ja edullisena työkaluna, joka edistää AVH:n jälkeistä kognitiivista ja emotionaalista toipumista. Tämä juontuu rakenteellisista ja toiminnallisista muutoksista ohimo- ja päälakilohkoalueiden verkostoissa, mitkä ovat ratkaisevia tunteiden käsittelyn, kielen sekä muistin kannalta. Tutkimus tuo uutta tietoa etenkin laulumusiikin kuuntelun vaikutuksesta kuntoutumiseen sekä laulujen käytöstä oppimisen ja muistin tukena, erityisesti afasiasta toipumisessa

The role of phonology in visual word recognition: evidence from Chinese

Posters - Letter/Word Processing V: abstract no. 5024The hypothesis of bidirectional coupling of orthography and phonology predicts that phonology plays a role in visual word recognition, as observed in the effects of feedforward and feedback spelling to sound consistency on lexical decision. However, because orthography and phonology are closely related in alphabetic languages (homophones in alphabetic languages are usually orthographically similar), it is difficult to exclude an influence of orthography on phonological effects in visual word recognition. Chinese languages contain many written homophones that are orthographically dissimilar, allowing a test of the claim that phonological effects can be independent of orthographic similarity. We report a study of visual word recognition in Chinese based on a mega-analysis of lexical decision performance with 500 characters. The results from multiple regression analyses, after controlling for orthographic frequency, stroke number, and radical frequency, showed main effects of feedforward and feedback consistency, as well as interactions between these variables and phonological frequency and number of homophones. Implications of these results for resonance models of visual word recognition are discussed.postprin

Interactive effects of orthography and semantics in Chinese picture naming

Posters - Language Production/Writing: abstract no. 4035Picture-naming performance in English and Dutch is enhanced by presentation of a word that is similar in form to the picture name. However, it is unclear whether facilitation has an orthographic or a phonological locus. We investigated the loci of the facilitation effect in Cantonese Chinese speakers by manipulating—at three SOAs (2100, 0, and 1100 msec)—semantic, orthographic, and phonological similarity. We identified an effect of orthographic facilitation that was independent of and larger than phonological facilitation across all SOAs. Semantic interference was also found at SOAs of 2100 and 0 msec. Critically, an interaction of semantics and orthography was observed at an SOA of 1100 msec. This interaction suggests that independent effects of orthographic facilitation on picture naming are located either at the level of semantic processing or at the lemma level and are not due to the activation of picture name segments at the level of phonological retrieval.postprin