Recognition memory and prefrontal cortex: dissociating recollection and familiarity processes using rTMS

Recognition memory can be supported by both the assessment of the familiarity of an item and by the recollection of the context in which an item was encountered. The neural substrates of these memory processes are controversial. To address these issues we applied repetitive transcranial magnetic stimulation (rTMS) over the right and left dorsolateral prefrontal cortex (DLPFC) of healthy subjects performing a remember/know task. rTMS disrupted familiarity judgments when applied before encoding of stimuli over both right and left DLPFC. rTMS disrupted recollection when applied before encoding of stimuli over the right DLPFC. These findings suggest that the DLPFC plays a critical role in recognition memory based on familiarity as well as recollection.     

rTMS stimulation on left DLPFC increases the correct recognition of memories for emotional target and distractor words

According to a recent hypothesis, the prefrontal cortex has been proposed as the site of emotional memory integration, because it is sensitive to the recognition of emotional contents. In the present research, we explored the role of the dorsolateral prefrontal cortex (DLPFC) in memory recognition processes for positive versus negative emotional stimuli when old (target) and new (distractor, either semantically related or unrelated to the target) stimuli were presented. The role of the DLPFC was analysed using an rTMS (repeated transcranial magnetic stimulation) paradigm that induced increased cortical activation of the left DLPFC. The subjects were required to perform a task that consisted of two experimental phases (i.e., an encoding and a recognition phase) in which the targets and the distractors were presented and recognition performance was measured. rTMS stimulation was provided over the left DLPFC during the recognition phase. We found that the rTMS stimulation affected the memory recognition of positive emotional material. Moreover, related and unrelated distractors were discarded better when they were positively valenced, and a more significant effect (i.e., increased performance) was produced in response to related distractors. This result suggests that the activation of the left DLPFC favours the memory recognition of positive emotional information, and that such activation is able to induce a more appropriate selective process to distinguish target from distractor stimuli in the presence of more complex processes (related distractors). The valence model of emotional cue processing may explain this increased performance by demonstrating the distinct role of the left hemisphere in the retrieval of positive emotional information.     

The contribution of the dorsolateral prefrontal cortex in full and divided encoding: a paired-pulse transcranial magnetic stimulation study

This research investigated the contribution of the dorsolateral prefrontal cortex (DLPFC) in the attentional resources in episodic encoding for both verbal and non-verbal material. Paired-pulse transcranial magnetic stimulations (TMS) were used to interfere transiently with either the left or right DLPFC during encoding under full attention (FA) or under divided attention (DA) in a recognition paradigm using words and random shapes. Participants recognized fewer items after TMS over the left DLPFC than over the right DLPFC during FA encoding. However, TMS over the left DLPFC did not impair performance when compared to sham condition. Conversely, participants produced fewer items after TMS over the right DLPFC in DA encoding compared to sham condition, but not compared to TMS over the left DLPFC. These effects were found for both words and random shapes. These results suggest that the right DLPFC play an important role in successful encoding with a concomitant task regardless of the type of material.     

The effect of bicephalic stimulation of the dorsolateral prefrontal cortex on the attentional bias for threat: A transcranial direct current stimulation study

Previous stimulation studies demonstrated that the dorsolateral prefrontal cortex (DLPFC) is involved in threat processing. According to a model of emotional processing, an unbalance between the two DLPFCs, with a hyperactivation of right frontal areas, is involved in the processing of negative emotions and genesis of anxiety. In the present study, we investigated the role of the right and left DLPFC in threat processing in healthy women who also completed the State-Trait Anxiety Inventory (STAI). We simultaneously modulated the activity of the right and left dorsolateral prefrontal cortex by applying bicephalic transcranial direct current stimulation (tDCS) before participants completed a modified version of the classic Posner task using threatening and nonthreatening stimuli as spatial cues. Anodal stimulation on the right DLPFC with a simultaneous cathodal stimulation over the left side induced a disengagement bias in individuals with low STAI scores and a facilitation bias in individuals with high STAI scores. Anodal stimulation on the left DLPFC with the simultaneous cathodal stimulation over the right side did not affect threat processing. The findings of the present study provided specific support to the hypothesis that unbalanced activation between left and right hemispheres with enhanced activation of the right DLPFC is critical in early top-down threat processing in healthy individuals.     

Brain activity during the encoding, retention, and retrieval of stimulus representations

Studies of delayed nonmatching-to-sample (DNMS) performance following lesions of the monkey cortex have revealed a critical circuit of brain regions involved in forming memories and retaining and retrieving stimulus representations. Using event-related functional magnetic resonance imaging (fMRI), we measured brain activity in 10 healthy human participants during performance of a trial-unique visual DNMS task using novel barcode stimuli. The event-related design enabled the identification of activity during the different phases of the task (encoding, retention, and retrieval). Several brain regions identified by monkey studies as being important for successful DNMS performance showed selective activity during the different phases, including the mediodorsal thalamic nucleus (encoding), ventrolateral prefrontal cortex (retention), and perirhinal cortex (retrieval). Regions showing sustained activity within trials included the ventromedial and dorsal prefrontal cortices and occipital cortex. The present study shows the utility of investigating performance on tasks derived from animal models to assist in the identification of brain regions involved in human recognition memory.     

Lateral and medial prefrontal contributions to emotion generation by semantic elaboration during episodic encoding

Memories for emotion-laden stimuli are remembered more accurately than those for neutral stimuli. Although this enhancement reflects stimulus-driven modulation of memory by emotions, functional neuroimaging evidence of the interacting mechanisms between emotions generated by intentional processes, such as semantic elaboration, and memory is scarce. The present fMRI study investigated how encoding-related activation is modulated by emotions generated during the process of semantic elaboration. During encoding with fMRI, healthy young adults viewed neutral (target) pictures either passively or with semantic elaboration. In semantic elaboration, participants imagined background stories related to the pictures. Encoding trials with semantic elaboration were subdivided into conditions in which participants imagined negative, positive, or neutral stories. One week later, memories for target pictures were tested. In behavioral results, memories for target pictures were significantly enhanced by semantic elaboration, compared to passive viewing, and the memory enhancement was more remarkable when negative or positive stories were imagined. fMRI results demonstrated that activations in the left inferior frontal gyrus and dorsal medial prefrontal cortex (dmPFC) were greater during the encoding of target pictures with semantic elaboration than those with passive viewing, and that these activations further increased during encoding with semantic elaboration of emotional stories than of neutral stories. Functional connectivity between the left inferior frontal gyrus and dmPFC/hippocampus during encoding significantly predicted retrieval accuracies of memories encoded with self-generated emotional stories. These findings suggest that networks including the left inferior frontal region, dmPFC, and hippocampus could contribute to the modulation of memories encoded with the emotion generation.     

Dorsolateral prefrontal cortex mediates working memory processes in motor skill learning

Neuroimaging studies have shown that the dorsolateral prefrontal cortex (DLPFC) is recruited during motor skill learning, which suggests the involvement of the DLPFC in working memory (WM) processes, such as selection and integration of motor representations temporarily stored in WM. However, direct evidence linking activation of the DLPFC to WM storage and manipulation during motor skill learning in real-time is rare. In this study, we conducted two experiments to investigate the causal role of DLPFC activity in WM storage and manipulation during motor skill learning under low and high WM-demand conditions. Participants received continuous theta burst stimulation (cTBS) and sham stimulation (crossover design) over the left DLPFC (experiment 1) or right DLPFC (experiment 2). Before and after stimulation, participants in both experiments performed a sequential finger-tapping (SFT) task containing repeated sequence (low-WM demand) and non-repeated sequence (high-WM demand) conditions which are used to study WM processes. The number of correct sequences (NoCS) and reproduction error rate were analyzed. Learning gains in NoCS improved significantly with the practice for both sequence types in the presence of either stimulation type. Compared to sham stimulation, cTBS over the left DLPFC resulted in significantly reduced learning gains in NoCS for non-repeated sequences. These results suggest that the left DLPFC contributes to WM manipulation during motor skill learning.     

Functional asymmetry of human prefrontal cortex: encoding and retrieval of verbally and nonverbally coded information

There are several views about the organization of memory functions in the human prefrontal cortex. One view assumes a process-specific brain lateralization according to different memory subprocesses, that is, encoding and retrieval. An alternative view emphasizes content-specific lateralization of brain systems involved in memory processes. This study addresses this apparent inconsistency between process- and content-specific lateralization of brain activity by investigating the effects of verbal and nonverbal encoding on prefrontal activations during encoding and retrieval of environmental novel sounds using fMRI. An intentional memory task was applied in which subjects were required either to judge the sounds' loudness (nonverbal encoding task) or to indicate whether or not a sound can be verbally described (verbal encoding task). Retrieval processes were examined in a subsequent yes/no recognition test. In the study phase the right posterior dorsolateral prefrontal cortex (PFC) was activated in both tasks. During verbal encoding additional activation of the left dorsolateral PFC was obtained. Retrieval-related fMRI activity varied as a function of encoding task: For the nonverbal task we detected an activation focus in the right posterior dorsolateral PFC whereas an activation in the left dorsolateral PFC was observed for the verbal task. These findings indicate that the right dorsolateral PFC is engaged in encoding of auditory information irrespective of encoding task. The lateralization of PFC activity during retrieval was shown to depend on the availability of verbal codes, with left hemispheric involvement for verbally and right hemispheric activation for nonverbally coded information.     

Working and long-term memory deficits in schizophrenia: is there a common prefrontal mechanism?

This study tested the hypothesis that dorsolateral prefrontal cortex deficits contribute to both working memory and long-term memory disturbances in schizophrenia. It also examined whether such deficits were more severe for verbal than nonverbal stimuli. Functional magnetic resonance imaging was used to assess cortical activation during performance of verbal and nonverbal versions of a working memory task and both encoding and recognition tasks in 38 individuals with schizophrenia and 48 healthy controls. Performance of both working memory and long-term memory tasks revealed disturbed dorsolateral prefrontal cortex activation in schizophrenia, although medial temporal deficits were also present. Some evidence was found for more severe cognitive and functional deficits with verbal than nonverbal stimuli, although these results were mixed.     

Neural substrates of successful working memory and long-term memory formation in a relational spatial memory task

Working memory (WM) tasks may involve brain activation actually implicated in long-term memory (LTM). In order to disentangle these two memory systems, we employed a combined WM/LTM task, using a spatial relational (object-location) memory paradigm and analyzed which brain areas were associated with successful performance for either task using fMRI. Critically, we corrected for the performance on the respective memory task when analyzing subsequent memory effects. The WM task consisted of a delayed-match-to-sample task assessed in an MRI scanner. Each trial consisted of an indoor or outdoor scene in which the exact configuration of four objects had to be remembered. After a short delay (7–13 s), the scene was presented from a different angle and spatial recognition for two objects was tested. After scanning, participants received an unexpected subsequent recognition memory (LTM) task, where the two previously unprobed objects were tested. Brain activity during encoding, delay phase and probe phase was analyzed based on WM and LTM performance. Results showed that successful WM performance, when corrected for LTM performance, was associated with greater activation in the inferior frontal gyrus and left fusiform gyrus during the early stage of the maintenance phase. A correct decision during the WM probe was accompanied by greater activation in a wide network, including bilateral hippocampus, right superior parietal gyrus and bilateral insula. No voxels exhibited supra-threshold activity during the encoding phase, and we did not find any differential activity for correct versus incorrect trials in the WM task when comparing LTM correct versus LTM incorrect trials.     

Brain activation while forming memories of fearful and neutral faces in women and men

Event-related functional MRI (fMRI) was used to assess brain activity during encoding of fearful and neutral faces in 12 women and 12 men. In a subsequent memory analysis, the authors separated successful from unsuccessful encoding of both types of faces, based on whether they were remembered or forgotten in a later recognition memory test. Overall, women and men recruited overlapping neural circuitries. Both sexes activated right-sided medial-temporal regions during successful encoding of fearful faces. Successful encoding of neutral faces was associated with left-sided lateral prefrontal and right-sided superior frontal activation in both sexes. In women, relatively greater encoding related activity for neutral faces was seen in the superior parietal and parahippocampal cortices. By contrast, men activated the left and right superior/middle frontal cortex more than women during successful encoding of the same neutral faces. These findings suggest that women and men use similar neural networks to encode facial information, with only subtle sex differences observed for neutral faces.     

FUNCTIONAL MAGNETIC RESONANCE IMAGING OF SEMANTIC MEMORY PROCESSES IN THE FRONTAL LOBES

Abstract— Frontal-lobe activation during semantic memory performance was examined using functional magnetic resonance imaging (fMRI), a noninvasive technique for localizing neural activity associated with cognitive function. Left inferior prefrontal cortex was more activated for semantic than for perceptual encoding of words, and for initial than for repeated semantic encoding of words. Decreased activation for semantic encoding of repeated words reflects repetition priming, that is, implicit retrieval of memory gained in the initial semantic encoding of a word. The left inferior prefrontal region may sub-serve semantic working memory processes that participate in semantic encoding and that have decreased demands when such encoding can be facilitated by recent semantic experience. These results demonstrate that fMRI can visualize changes in an individual's brain function associated with the encoding and retrieval of new memories.     

PET studies of encoding and retrieval: The HERA model

We review positron emission tomography (PET) studies whose results converge on the hemispheric encoding/retrieval asymmetry (HERA) model of the involvement of prefrontal cortical regions in the processes of human memory. The model holds that the left prefrontal cortex is differentially more involved in retrieval of information from semantic memory, and in simultaneously encoding novel aspects of the retrieved information into episodic memory, than is the right prefrontal cortex. The right prefrontal cortex, on the other hand, is differentially more involved in episodic memory retrieval than is the left prefrontal cortex. This general pattern holds for different kinds of information (e.g., verbal materials, pictures, faces) and a variety of conditions of encoding and retrieval.     

Unraveling Brain Functional Connectivity of encoding and retrieval in the context of education

Human memory is an enigmatic component of cognition which many researchers have attempted to comprehend. Accumulating studies on functional connectivity see brain as a complex dynamic unit with positively and negatively correlated networks in perfect coherence during a task. We aimed to examine coherence of network connectivity during visual memory encoding and retrieval in the context of education. School Educated (SE) and College Educated (CE) healthy volunteers (n = 60) were recruited and assessed for visual encoding and retrieval. Functional connectivity using seed to voxel based connectivity analysis of the posterior cingulate cortex (PCC) was evaluated. We noticed that there were reciprocal dynamic changes in both dorsolateral prefrontal cortex (DLPFC) region and PCC regions during working memory encoding and retrieval. In agreement with the previous studies, there were more positively correlated regions during retrieval compared to encoding. The default mode network (DMN) networks showed greater negative correlations during more attentive task of visual encoding. In tune with the recent studies on cognitive reserve we also found that number of years of education was a significant factor influencing working memory connectivity. SE had higher positive correlation to DLPFC region and lower negative correlation to DMN in comparison with CE during encoding and retrieval.     

Transcranial direct current stimulation versus intermittent theta-burst stimulation for the improvement of working memory performance

Non-invasive brain stimulation (NIBS) techniques have been increasingly used over the dorsolateral prefrontal cortex (DLPFC) to enhance working memory (WM) performance. Notwithstanding, NIBS protocols have shown either small or inconclusive cognitive effects on healthy and neuropsychiatric samples. Therefore, we assessed working memory performance and safety of transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), and both therapies combined vs placebo over the neuronavigated left DLPFC of healthy participants. Twenty-four subjects were included to randomly undergo four sessions of NIBS, once a week: tDCS alone, iTBS alone, combined interventions and placebo. The 2-back task and an adverse effect scale were applied after each NIBS session. Results revealed a significantly faster response for iTBS (b= -21.49, p= 0.04), but not for tDCS and for the interaction tDCS vs. iTBS (b= 13.67, p= 0.26 and b= 40.5, p= 0.20, respectively). No changes were observed for accuracy and no serious adverse effects were found among protocols. Although tolerable, an absence of synergistic effects for the combined protocol was seen. Nonetheless, future trials accessing different outcomes for the combined protocols, as well as studies investigating iTBS over the left DLPFC for cognition and exploring sources of variability for tDCS are encouraged.     

Developmental differences in prefrontal activation during working memory maintenance and manipulation for different memory loads

The ability to keep information active in working memory is one of the cornerstones of cognitive development. Prior studies have demonstrated that regions which are important for working memory performance in adults, such as dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and superior parietal cortex, become increasingly engaged across school-aged development. The primary goal of the present functional MRI study was to investigate the involvement of these regions in the development of working memory manipulation relative to maintenance functions under different loads. We measured activation in DLPFC, VLPFC, and superior parietal cortex during the delay period of a verbal working memory task in 11-13-year-old children and young adults. We found evidence for age-related behavioral improvements in working memory and functional changes within DLPFC and VLPFC activation patterns. Although activation profiles of DLPFC and VLPFC were similar, group differences were most pronounced for right DLPFC. Consistent with prior studies, right DLPFC showed an interaction between age and condition (i.e. manipulation versus maintenance), specifically at the lower loads. This interaction was characterized by increased activation for manipulation relative to maintenance trials in adults compared to children. In contrast, we did not observe a significant age-dependent load sensitivity. These results suggest that age-related differences in the right DLPFC are specific to working memory manipulation and are not related to task difficulty and/or differences in short-term memory capacity.     

背外侧前额叶对主动遗忘负性社会反馈的作用：针对抑郁症的TMS研究

抑郁症患者的负性心境可能源于其抑制功能障碍。患者在主动遗忘负性材料时无法有效调用背外侧前额叶(the dorsolateral prefrontal cortex, DLPFC)等负责抑制控制的额叶脑网络。同时, 患者对社会信息的加工比对非社会信息的加工存在更明显的认知神经障碍, 很难主动遗忘对自己不利的社会反馈信息。为了提高抑郁症患者对负性社会反馈的主动遗忘能力, 本研究采用经颅磁刺激技术(transcranial magnetic stimulation, TMS), 考察抑郁症患者在左侧(n = 32)或右侧DLPFC (n = 30)被激活后其记忆控制能力的改变。结果表明, 当患者的DLPFC被TMS激活时, 他们对社会拒绝的回忆正确率与健康对照组(n = 31)无差异, 且TMS激活右侧DLPFC还改善了患者对他人的社会态度。本研究是采用TMS提高抑郁症患者主动遗忘能力的首次尝试, 研究结果不但支持了DLPFC与记忆控制功能的因果关系, 还为临床治疗抑郁症、创伤后应激障碍、药物成瘾等患者的记忆控制缺陷提供了明确的神经靶点。     

Content-specific source encoding in the human medial temporal lobe

Although the medial temporal lobe (MTL) is known to be essential for episodic encoding, the contributions of individual MTL subregions remain unclear. Data from recognition memory studies have provided evidence that the hippocampus supports relational encoding important for later episodic recollection, whereas the perirhinal cortex has been linked with encoding that supports later item familiarity. However, extant data also strongly implicate the perirhinal cortex in object processing and encoding, suggesting that perirhinal processes may contribute to later episodic recollection of object source details. To investigate this possibility, encoding activation in MTL subregions was analyzed on the basis of subsequent memory outcome while participants processed novel scenes paired with 1 of 6 repeating objects. Specifically, encoding activation correlating with later successful scene recognition memory was evaluated against that of source recollection for the object paired with the scene during encoding. In contrast to studies reporting a link between perirhinal cortex and item familiarity, it was found that encoding activation in the right perirhinal cortex correlates with successful recollection of the paired object. Furthermore, other MTL subregions also exhibited content-specific source encoding patterns of activation, suggesting that MTL subsequent memory effects are sensitive to stimulus category.     

编码任务对来源记忆的影响:一项事件相关电位研究

本研究采用ERPs技术,探讨编码任务对来源记忆的影响及其神经机制。在学习阶段,被试进行两种编码操作：匹配判断任务和大小判断任务;在测验阶段,让被试进行来源判断任务。行为结果发现：在编码阶段,匹配判断任务比大小判断任务需要更长的时间;在测验阶段,匹配判断任务在“项目旧/背景旧”和“部分旧”条件的正确率显著高于大小判断任务,匹配判断任务在“项目旧/背景旧”条件的反应时显著短于大小判断任务。测验阶段ERPs结果发现：两种编码任务的新旧效应在200~700ms均有较广泛的头皮分布,而在700~1100ms呈前额皮层最大化分布;匹配判断任务的新旧效应比大小判断任务更大,表现在600~700ms的FPz电极以及700~800ms的Pz、P4电极。由此可见,在来源记忆中,编码任务影响来源记忆,主要表现在后部顶区位置;晚期前额皮层新旧效应不受任务难度因素的影响。     

Noninvasive brain stimulation over M1 and DLPFC cortex enhances the learning of bimanual isometric force control

Motor learning plays an important role in upper-limb function and the recovery of lost functionality. This study aimed to investigate the relative impact of transcranial direct current stimulation (tDCS) on learning in relation to the left primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC) during bimanual isometric force-control tasks performed with both hands under different task constraints. In a single-blind cross-over design, 20 right-handed participants were randomly assigned to either the M1 group (n = 10; mean age, 22.90 ± 1.66 years, mean ± standard deviation) or the DLPFC group (n = 10; mean age, 23.20 ± 1.54 years). Each participant received 30 min of tDCS (anodal or sham, applied randomly in two experiments) while performing the bimanual force control tasks. Anodal tDCS of the M1 improved the accuracy of maintenance and rhythmic alteration of force tasks, while anodal tDCS of the DLPFC improved only the maintenance of the force control tasks compared with sham tDCS. Hence, tDCS over the left M1 and DLPFC has a beneficial effect on the learning of bimanual force control.