Prefrontal control of familiarity and recollection in working memory

Left inferior frontal gyrus (IFG) is a critical neural substrate for the resolution of proactive interference (PI) in working memory. We hypothesized that left IFG achieves this by controlling the influence of familiarity- versus recollection-based information about memory probes. Consistent with this idea, we observed evidence for an early (200 msec)-peaking signal corresponding to memory probe familiarity and a late (500 msec)-resolving signal corresponding to full accrual of trial-related contextual ("recollection-based") information. Next, we applied brief trains of repetitive transcranial magnetic stimulation (rTMS) time locked to these mnemonic signals, to left IFG and to a control region. Only early rTMS of left IFG produced a modulation of the false alarm rate for high-PI probes. Additionally, the magnitude of this effect was predicted by individual differences in susceptibility to PI. These results suggest that left IFG-based control may bias the influence of familiarity- and recollection-based signals on recognition decisions

Memory and cognition in schizophrenia.

Episodic memory deficits are consistently documented as a core aspect of cognitive dysfunction in schizophrenia patients, present from the onset of the illness and strongly associated with functional disability. Over the past decade, research using approaches from experimental cognitive neuroscience revealed disproportionate episodic memory impairments in schizophrenia (Sz) under high cognitive demand relational encoding conditions and relatively unimpaired performance under item-specific encoding conditions. These specific deficits in component processes of episodic memory reflect impaired activation and connectivity within specific elements of frontal-medial temporal lobe circuits, with a central role for the dorsolateral prefrontal cortex (DLPFC), relatively intact function of ventrolateral prefrontal cortex and variable results in the hippocampus. We propose that memory deficits can be understood within the broader context of cognitive deficits in Sz, where impaired DLPFC-related cognitive control has a broad impact across multiple cognitive domains. The therapeutic implications of these findings are discussed

MAO-A and the EEG Recognition Memory Signal in Left Parietal Cortex

A key part of episodic memory, or memory for the events of our lives, is recognition memory. Recognition memory is the ability to remember previously encountered stimuli. Studies have linked recognition memory to the old/new effect, an EEG indicator of stimulus familiarity. Monoamine oxidase A (MAO-A) is an enzyme that catalyzes monoamines, leading to the depletion of norepinephrine, epinephrine, serotonin, and dopamine. MAO-A is more efficiently transcribed in individuals with a 4 repeating sequence variation (4R) of the MAO-A gene leading to less monoamine availability. As many of these monoamines have been linked to episodic memory, we hypothesized that individuals homozygous for the 4R MAO-A polymorphism would show differences in mean EEG signal amplitudes during recognition memory. EEG data was recorded as participants viewed both new words and words that had been previously presented. Our results show that mean peak amplitudes over the left parietal cortex 500-800 ms post-stimulus presentation for hits were greater than those for correct rejections, indicating the old/new effect. Critically, our results revealed an interaction between mean hit and correct rejection amplitude over the left parietal cortex and MAO-A group. Individuals homozygous for the 4R variation (the High MAO-A group) do not show an old/new effect due to increased correct rejection amplitudes. These results suggest that less monoamine availability leads to new stimuli being identified as old by the left parietal cortex

Neuropsychological Generation of Source Amnesia: An Episodic Memory Disorder of the Frontal Brain

Source amnesia is an explicit memory (declarative) disorder, particularly episodic, where source or contextual information concerning facts is severely distorted and/or unable to be recalled. This paper reviews the literature on source amnesia, including memory distrust syndrome, and its accepted correlation with the medial diencephalic system and the temporal lobes, and the suggested linkage between the frontal lobes, including special interest with the prefrontal cortex. Posthypnotic induction was the first presentation of source amnesia identified in the literature. The Wisconsin Cart Sorting Test (WCST), Positron Emission Topography (PET), Phonemic Verbal Fluency Test, Stroop Color Word Interference Test, and explicit and implicit memory tests are defined and linked to empirical research on amnesiacs

Distinct patterns of neural activity during memory formation of nonwords versus words

Research into the neural underpinnings of memory formation has focused on the encoding of familiar verbal information. Here, we address how the brain supports the encoding of novel information that does not have meaning. Electrical brain activity was recorded from the scalps of healthy young adults while they performed an incidental encoding task (syllable judgments) on separate series of words and "nonwords" (nonsense letter strings that are orthographically legal and pronounceable). Memory for the items was then probed with a recognition memory test. For words as well as nonwords, event-related potentials differed depending on whether an item would subsequently be remembered or forgotten. However, the polarity and timing of the effect varied across item type. For words, subsequently remembered items showed the Usually observed positive-going, frontally distributed modulation from around 600 msec after word onset. For nonwords, by contrast, a negative-going, spatially widespread modulation predicted encoding success from 1000 rnsec onward. Nonwords also showed a modulation shortly after item onset. These findings imply that the brain supports the encoding of familiar and unfamiliar letter strings in qualitatively different ways, including the engagement of distinct neural activity at different points in time. The processing of semantic attributes plays an important role in the encoding of words and the associated positive frontal modulation

The Neural Substrates of Memory Suppression: A fMRI Exploration of Directed Forgetting

The directed forgetting paradigm is frequently used to determine the ability to voluntarily suppress information. However, little is known about brain areas associated with information to forget. The present study used functional magnetic resonance imaging to determine brain activity during the encoding and retrieval phases of an item-method directed forgetting recognition task with neutral verbal material in order to apprehend all processing stages that information to forget and to remember undergoes. We hypothesized that regions supporting few selective processes, namely recollection and familiarity memory processes, working memory, inhibitory and selection processes should be differentially activated during the processing of to-be-remembered and to-be-forgotten items. Successful encoding and retrieval of items to remember engaged the entorhinal cortex, the hippocampus, the anterior medial prefrontal cortex, the left inferior parietal cortex, the posterior cingulate cortex and the precuneus; this set of regions is well known to support deep and associative encoding and retrieval processes in episodic memory. For items to forget, encoding was associated with higher activation in the right middle frontal and posterior parietal cortex, regions known to intervene in attentional control. Items to forget but nevertheless correctly recognized at retrieval yielded activation in the dorsomedial thalamus, associated with familiarity-based memory processes and in the posterior intraparietal sulcus and the anterior cingulate cortex, involved in attentional processes

Subjective experience of episodic memory and metacognition: a neurodevelopmental approach.

Episodic retrieval is characterized by the subjective experience of remembering. This experience enables the co-ordination of memory retrieval processes and can be acted on metacognitively. In successful retrieval, the feeling of remembering may be accompanied by recall of important contextual information. On the other hand, when people fail (or struggle) to retrieve information, other feelings, thoughts, and information may come to mind. In this review, we examine the subjective and metacognitive basis of episodic memory function from a neurodevelopmental perspective, looking at recollection paradigms (such as source memory, and the report of recollective experience) and metacognitive paradigms such as the feeling of knowing). We start by considering healthy development, and provide a brief review of the development of episodic memory, with a particular focus on the ability of children to report first-person experiences of remembering. We then consider neurodevelopmental disorders (NDDs) such as amnesia acquired in infancy, autism, Williams syndrome, Down syndrome, or 22q11.2 deletion syndrome. This review shows that different episodic processes develop at different rates, and that across a broad set of different NDDs there are various types of episodic memory impairment, each with possibly a different character. This literature is in agreement with the idea that episodic memory is a multifaceted process

Re-Examining the Role of the Default Network During Controlled Processing

Activation of the default network (DN) during externally-directed cognitive control tasks has been associated with off-task behaviors and poor task performance. Recently, evidence has suggested that DN activation may be associated with better cognitive control when access to stored representational knowledge, a putative DN function, is congruent with task goals (Spreng et al., 2014). Near-ceiling behavioral performance in this earlier study precluded analysis of incorrect trials. We address this limitation by increasing cognitive control demands. Healthy young adults (N=28) were scanned using fMRI while performing a working memory task. Famous and anonymous face stimuli were used to contrast high versus low access to stored representational knowledge, respectively. Differential DN activation was observed during correct and incorrect trials when famous faces were goal-relevant, or distractors. These results provide further evidence that the DN is not a task negative network, but can support cognitive control when access to stored representations is goal-congruent

Separating the brain regions involved in recollection and familiarity in recognition memory

The neural substrates of recognition memory retrieval were examined in a functional magnetic resonance imaging study designed to separate activity related to recollection from that related to continuous variations in familiarity. Across a variety of brain regions, the neural signature of recollection was found to be distinct from familiarity, demonstrating that recollection cannot be attributed to familiarity strength. In the prefrontal cortex, an anterior medial region was related to recollection, but lateral regions, including the anterior and dorsolateral prefrontal cortex, were related to familiarity. Along the lateral parietal cortex, two functionally distinct regions were also observed: a lateral parietal/temporal region related to recollection and a more superior parietal region involved in familiarity. Similarly, in medial parietal regions, the posterior cingulate was related to recollection, whereas the precuneus was related to familiarity. The hippocampus was related to recollection, but also exhibited an inverse relationship to familiarity-driven recognition confidence. The results indicate that recollection and familiarity rely on different networks of brain regions and provide insights into the functional roles of different regions involved in episodic recognition memory. The neural substrates of recognition memory retrieval were examined in a functional magnetic resonance imaging study designed to separate activity related to recollection from that related to continuous variations in familiarity. Across a variety of brain regions, the neural signature of recollection was found to be distinct from familiarity, demonstrating that recollection cannot be attributed to familiarity strength. In the prefrontal cortex, an anterior medial region was related to recollection, but lateral regions, including the anterior and dorsolateral prefrontal cortex, were related to familiarity. Along the lateral parietal cortex, two functionally distinct regions were also observed: a lateral parietal/temporal region related to recollection and a more superior parietal region involved in familiarity. Similarly, in medial parietal regions, the posterior cingulate was related to recollection, whereas the precuneus was related to familiarity. The hippocampus was related to recollection, but also exhibited an inverse relationship to familiarity-driven recognition confidence. The results indicate that recollection and familiarity rely on different networks of brain regions and provide insights into the functional roles of different regions involved in episodic recognition memory

Ageing and Episodic Memory: Combining Neuropsychological and Event-Related Potential Approaches to Investigate Strategic Retrieval

This thesis investigates the effect of normal ageing on the strategies adopted during episodic memory retrieval, using a combination of neuropsychological profiling and neuroimaging data measured during performance on a source memory exclusion task. The exclusion task is a type of source memory task where participants distinguish between targets (studied items from one source e.g. female voice), non-targets (studied items from another source e.g. male voice) and new items. Unlike a source memory task where three separate buttons are pressed for each item at test, in the exclusion task one button is pressed for targets and a second for non-target and new items. As this task is more complex than a normal source memory paradigm and also allows participants to perform the task in more than one way, it places high emphasis on the use of strategies to facilitate retrieval and is therefore ideal for investigating strategic retrieval. Previous source memory studies have shown that while older adults are reasonably good at recognising whether items are old or new, they show marked impairments at remembering the source in which items were presented at study. Dual process theories propose that the age-related decline in source memory occurs because recollection becomes impaired with ageing whereas familiarity remains relatively spared. The results reported in this thesis support dual process theory. Experiment 2a showed that, behaviourally, as expected, the young outperformed the elderly. Event-related potentials (ERPs), recorded while a source memory exclusion test was performed, revealed that both young and older adults showed bilateral frontal and left parietal old/new effects, thought to index familiarity and recollection respectively. Importantly, the magnitude of the left parietal effect was significantly reduced in the older adults. The ERP findings also suggested that dual process theories represent an oversimplification of episodic memory decline with age. In Experiment 1a, three temporally and topographically distinct late frontal old/new effects were present in the younger adults: a bilateral anterior frontal effect (450-900ms post stimulus), a right prefrontal effect (900-1300ms) and a right frontal effect (1300-2000ms). Significant positive correlations between the magnitude of these effects and performance on neuropsychological tests of executive functioning in Experiment 1b, revealed that the bilateral anterior frontal effect was related to working memory, strategy use and planning; the right prefrontal effect was related to working memory and planning while the right frontal effect was related to planning. By contrast, the older adults in Experiment 2a only produced the right frontal effect, which correlated with planning across all three time windows in Experiment 2c. Post-retrieval monitoring in older adults therefore appeared to be qualitatively different than their younger counterparts. Performance on the neuropsychological tests in Experiment 2b, revealed that the older adults’ working memory and strategy use was impaired compared to the young, whereas planning was relatively intact, suggesting that age-related differences in post retrieval processing may be due to reduced executive functioning in older adults. Identifying distinct late frontal effects and demonstrating a relationship between these effects and specific executive functions is a novel finding. The presence of a left parietal target greater than non-target difference in the young adults from Experiment 1a and 2a was interpreted as the young reducing recollection of irrelevant non-target information. The modulation did not differ in magnitude for targets and non-targets in the elderly adults from Experiment 2a, suggesting they were less able to reduce activation of goal irrelevant non-target information. The results in the young adults from Experiment 1a also highlight the importance of considering the context of source information on the processes engaged at retrieval. The bilateral frontal effect was significant for the retrieval of the intrinsic context (source information inherent to the studied item), but not the extrinsic context (source information not inherent to the studied item). This finding was interpreted within a unitisation framework, where the intrinsic context became unitised with the item and enhanced familiarity based remembering. The findings also highlight that in order to fully understand post retrieval processing in both young and old adults, focus should move away from examining quantitative differences in the right frontal effect over long time periods and instead identify qualitatively distinct late frontal effects that may reflect the engagement of various executive functions over time