Verbal Working Memory Dysfunction in Schizophrenia: An fMRI Investigation

Impaired processing of working memory information is one of the cognitive deficits seen in patients with schizophrenia. This study aims at corroborating the differences in the brain activities involved in the process of working memory between patients with schizophrenia and the controls. Twelve patients with schizophrenia and 11 controls participated in the study. Functional magnetic resonance imaging (fMRI) was used to assess cortical activities during the performance of a two-back verbal working memory paradigm using the Korean alphabet as mnemonic content. Group analysis revealed that inferior fontal, middle frontal, and superior temporal region showed decreased cortical activities in the patient group compared to those of the controls. This study showed a decreased activation in inferior fontal (BA 47), middle frontal (BA 6), and superior temporal (BA 22/38) neural networks from the patient group and confirmed the earlier findings on the impaired working memory of schizophrenic patients in the fMRI investigation.     

Assembling and encoding word representations: fMRI subsequent memory effects implicate a role for phonological control

Novel word learning is central to the flexibility inherent in the human language capacity. Word learning may partially depend on long-term memory formation during the assembly of phonological representations from orthographic inputs. In the present study, event-related functional magnetic resonance imaging (fMRI) examined the contributions of phonological control-a component of the verbal working memory system-to phonological assembly and word learning. Subjects were scanned while making syllable decisions about visually presented familiar (English) and novel (pseudo-English and Foreign) words, a task that required retrieval and analysis of existing phonological codes or the assembly and analysis of novel representations. Results revealed that left inferior prefrontal cortex (LIPC) and bilateral parietal cortices were differentially engaged during the processing of novel words, suggesting that this circuit is recruited during phonological assembly. A subsequent memory analysis that examined the relation between fMRI signal and the subject's ability to later remember the words (a measure of effective memory formation) revealed that the magnitude of activation in LIPC, bilateral superior parietal, and left inferior parietal cortices was positively correlated with later memory. Moreover, although the magnitude of the subsequent memory effect in parietal cortex was not significantly affected by word type, this effect was greater in posterior LIPC for novel (pseudo-English) than for familiar (English) words. In the course of subserving the assembly of novel word representations, the phonological (articulatory) control component of the phonological system appears to play a central role in the encoding of novel words into long-term memory.     

Letters persistence after physical offset: Visual word form area and left planum temporale. An fMRI study

Iconic memory is a high‐capacity low‐duration visual memory store that allows the persistence of a visual stimulus after its offset. The categorical nature of this store has been extensively debated. This study provides functional magnetic resonance imaging evidence for brain regions underlying the persistence of postcategorical representations of visual stimuli. In a partial report paradigm, subjects matched a cued row of a 3 × 3 array of letters (postcategorical stimuli) or false fonts (precategorical stimuli) with a subsequent triplet of stimuli. The cued row was indicated by two visual flankers presented at the onset (physical stimulus readout) or after the offset of the array (iconic memory readout). The left planum temporale showed a greater modulation of the source of readout (iconic memory vs. physical stimulus) when letters were presented compared to false fonts. This is a multimodal brain region responsible for matching incoming acoustic and visual patterns with acoustic pattern templates. These findings suggest that letters persist after their physical offset in an abstract postcategorical representation. A targeted region of interest analysis revealed a similar pattern of activation in the Visual Word Form Area. These results suggest that multiple higher‐order visual areas mediate iconic memory for postcategorical stimuli. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Representation of visual numerosity information during working memory in humans: An fMRI decoding study

Both animal and human studies on numerosity have shown the importance of the parietal cortex for numerosity processing. However, most studies have focused on the perceptual processing of numerosity. Still, it is unclear how and where numerosity information is coded when this information is retained during a working memory delay phase. Such temporal storage could be realized by the same structures as perceptual processes, or be transformed to a more abstract representation, potentially involving prefrontal regions. FMRI decoding studies allow the identification of brain areas that exhibit multi‐voxel activation patterns specific to the content of working memory. Here, we used an assumption‐free searchlight‐decoding approach to test where numerosity‐specific codes can be found during a 12 s retention period. Participants (n = 24) performed a retro‐cue delayed match‐to‐sample task, in which numerosity information was presented as visual dot arrays. We found mnemonic numerosity‐specific activation in the right lateral portion of the intraparietal sulcus; an area well‐known for perceptual processing of numerosity. The applied retro‐cue design dissociated working memory delay activity from perceptual processes and showed that the intraparietal sulcus also maintained working memory representation independent of perception.     

Social working memory and its distinctive link to social cognitive ability: an fMRI study

Engaging social working memory (SWM) during effortful social cognition has been associated with neural activation in two neurocognitive systems: the medial frontoparietal system and the lateral frontoparietal system. However, the respective roles played by these systems in SWM remain unknown. Results from this study demonstrate that only the medial frontoparietal system supports the social cognitive demands managed in SWM. In contrast, the lateral frontoparietal system supports the non-social cognitive demands that are needed for task performance, but that are independent of the social cognitive computations. Moreover, parametric increases in the medial frontoparietal system, but not the lateral frontoparietal system, in response to SWM load predicted performance on a challenging measure of perspective-taking. Thus, the medial frontoparietal system may uniquely support social cognitive processes in working memory and the working memory demands afforded by effortful social cognition, such as the need to track another person’s perspective in mind.     

Dyslexic Children Show Short-Term Memory Deficits in Phonological Storage and Serial Rehearsal: An fMRI Study

Dyslexia is primarily associated with a phonological processing deficit. However, the clinical manifestation also includes a reduced verbal working memory (WM) span. It is unclear whether this WM impairment is caused by the phonological deficit or a distinct WM deficit. The main aim of this study was to investigate neuronal activation related to phonological storage and rehearsal of serial order in WM in a sample of 13-year-old dyslexic children compared with age-matched nondyslexic children. A sequential verbal WM task with two tasks was used. In the Letter Probe task, the probe consisted of a single letter and the judgment was for the presence or absence of that letter in the prior sequence of six letters. In the Sequence Probe (SP) task, the probe consisted of all six letters and the judgment was for a match of their serial order with the temporal order in the prior sequence. Group analyses as well as single-subject analysis were performed with the statistical parametric mapping software SPM2. In the Letter Probe task, the dyslexic readers showed reduced activation in the left precentral gyrus (BA6) compared to control group. In the Sequence Probe task, the dyslexic readers showed reduced activation in the prefrontal cortex and the superior parietal cortex (BA7) compared to the control subjects. Our findings suggest that a verbal WM impairment in dyslexia involves an extended neural network including the prefrontal cortex and the superior parietal cortex. Reduced activation in the left BA6 in both the Letter Probe and Sequence Probe tasks may be caused by a deficit in phonological processing. However, reduced bilateral activation in the BA7 in the Sequence Probe task only could indicate a distinct working memory deficit in dyslexia associated with temporal order processing.     

fMRI study comparing names versus pictures of objects

We performed an fMRI one-back recognition study aimed at distinguishing the semantic versus perceptual aspects of how objects and their written forms are processed. There were three types of visually presented items: pictures (schematic drawings of objects); words identifying these objects; and a mixed condition in which pictures were interleaved with words. A semantic decision about object identity was required when pictures were interleaved with words. This condition, contrasted with the other two, invoked a larger signal in multiple areas, including frontal cortex, bilateral occipitotemporal cortex, and the right middle temporal gyrus. We propose that the left occipitotemporal and right temporal activations are indicative of the neural substrate mediating picture-word conversions, whereas the frontal activations reflect the coordinating functions of the central executive.     

Dissociating age-related changes in cognitive strategy and neural efficiency using event-related fMRI

We used event-related fMRI to measure brain activity while younger and older adults performed an item-recognition task in which the memory-set size varied between 1 and 8 letters. Each trial was composed of a 4-second encoding period in which subjects viewed random letter strings, a 12-second retention period and a 2-second retrieval period in which subjects decided whether a single probe letter was or was not part of the memory set. For both groups, reaction time increased and accuracy decreased with increasing memory set-size. There were minimal age-related differences in activation patterns with increasing memory set-size in prefrontal cortex (PFC). Regression analyses of individual subjects' performance and cortical activity indicated that speed and accuracy accounted for considerable variance in dorsal and ventral PFC activity during encoding and retrieval. These results suggest that younger and older adults utilize similar working memory (WM) strategies to accommodate increasing memory demand. They support a model of cognitive slowing in which processing rate is related to neural efficiency.     

轻度认知障碍工作记忆的fMRI研究

目的 :运用血氧水平依赖 (bloodoxygenationleveldependent ,BOLD)法功能磁共振成像 (functionalmagneticresonanceimaging ,fMRI)对轻度认知障碍 (mildcognitiveimpairment ,MCI)与正常对照组在记忆的激活区域范围及强度方面进行比较。方法 :对 6例MCI患者 ,8例认知正常老人进行神经心理学测试 ,在 1 5TPick磁共振扫描仪上进行记忆过程中的EPI序列的扫描 ,并运用相关软件分析所得图像及数据。结果 :MCI患者在颞叶激活范围比正常对照组小 ,时间 信号强度变化曲线亦有差异 ,右侧颞叶激活的范围和强度均高于左侧。结论 :MCI患者的记忆功能下降在fMRI上主要表现为颞叶激活范围的变化及激活强度的下降 ,颞叶可能是MCI记忆功能下降反应比较敏感的区域。     

Top-down influences on lexical selection during spoken word production: A 4T fMRI investigation of refractory effects in picture naming

Spoken word production is assumed to involve stages of processing in which activation spreads through layers of units comprising lexical-conceptual knowledge and their corresponding phonological word forms. Using high-field (4T) functional magnetic resonance imaging (fMRI), we assessed whether the relationship between these stages is strictly serial or involves cascaded-interactive processing, and whether central (decision/control) processing mechanisms are involved in lexical selection. Participants performed the competitor priming paradigm in which distractor words, named from a definition and semantically related to a subsequently presented target picture, slow picture-naming latency compared to that with unrelated words. The paradigm intersperses two trials between the definition and the picture to be named, temporally separating activation in the word perception and production networks. Priming semantic competitors of target picture names significantly increased activation in the left posterior temporal cortex, and to a lesser extent the left middle temporal cortex, consistent with the predictions of cascaded-interactive models of lexical access. In addition, extensive activation was detected in the anterior cingulate and pars orbitalis of the inferior frontal gyrus. The findings indicate that lexical selection during competitor priming is biased by top-down mechanisms to reverse associations between primed distractor words and target pictures to select words that meet the current goal of speech.     

Working memory representation in atypical language dominance

One of the most important factors controlling material specific processing in the human brain is language dominance, i.e. hemispheric specialization in semantic processes. Although previous studies have shown that lateralized long-term memory processes in the medial temporal lobes are modified in subjects with atypical (right) language dominance, the effect of language dominance on the neural basis of working memory (WM) has remained unknown. Here, we used functional MRI (fMRI) to study the impact of language dominance on the neural representation of WM. We conducted an n-back task in three different load conditions and with both verbal and nonverbal (spatial) material in matched groups of left and right language dominant subjects. This approach allowed us to investigate regions showing significant interactions between language dominance and material. Overall, right dominant subjects showed an increased inter-individual variability of WM-related activations. Verbal WM involved more pronounced activation of the left fusiform cortex in left dominant subjects and of the right inferior parietal lobule in the right dominant group. Spatial WM, on the other hand, induced activation of right hemispheric regions in left dominant subjects, but no specific activations in right dominant subjects. Taken together, these findings indicate that the neural basis of verbal WM processes depends on language dominance and is more mutable in right dominant subjects. The increased variability in right dominant subjects strongly suggests that a standard network of material-dependent WM processes exists in left dominant subjects, and that right dominant subjects use variable alternative networks.     

慢性失眠患者数字工作记忆的功能磁共振研究

目的 探讨慢性失眠患者数字工作记忆神经网络连接的改变.方法 采用组块设计方法,分别对40例慢性失眠患者(失眠组)及50例正常睡眠者(对照组)进行数字工作记忆状态下功能磁共振扫描,比较两组受试者在数字工作记忆中反应时间及正确率以及编码、维持、提取阶段脑区激活强度的改变.结果 失眠组与对照组数字工作记忆正确率的比较差异无统计学意义(P＞0.05),失眠组反应时间明显增加,差异有统计学意义(P＜0.01).慢性失眠患者在数字工作记忆编码期激活强度增强的脑区为左侧壳核、豆状核、顶下小叶及右侧尾状核、右枕叶;维持期激活强度增强的脑区为右侧额叶,左侧额叶及额叶内侧面,而左侧额上回激活强度有所下降;提取期激活强度增强的脑区为右额下回及右顶下缘角回,而激活轻度下降的脑区则有左内侧额上回、左岛叶、左后扣带回、左颞上回、左额上回及右颞叶、右后扣带回.结论 慢性失眠患者在数字工作记忆的各阶段,脑区激活强度较健康人有所改变:大脑皮质和皮质下结构广泛受损,即其神经网络连接发生明显改变.     

An fMRI investigation of working memory and sadness in females with bipolar disorder: a brief report

Objective: Functional magnetic resonance imaging (fMRI) studies have documented abnormalities in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex in bipolar disorder in the context of working memory tasks. It is increasingly recognized that DLPFC regions play a role in mood regulation and the integration of emotion and cognition. The purpose of the present study was to investigate with fMRI the interaction between acute sadness and working memory functioning in individuals with bipolar disorder. Methods: Nine depressed individuals with DSM‐IV bipolar I disorder (BP‐I) and 17 healthy control participants matched for age, gender, education, and IQ completed a 2‐back working memory paradigm under no mood induction, neutral state, or acute sadness conditions while undergoing fMRI scanning. Functional MRI data were analyzed with SPM2 using a random‐effects model. Results: Behaviorally, BP‐I subjects performed equally well as control participants on the 2‐back working memory paradigm. Compared to control participants, individuals with BP‐I were characterized by more sadness‐specific activation increases in the left DLPFC (BA 9/46) and left dorsal anterior cingulate (dACC). Conclusions: Our study documents sadness‐specific abnormalities in the left DLPFC and dACC in bipolar disorder that suggest difficulties in the integration of emotion (sadness) and cognition. These preliminary findings require further corroboration with larger sample sizes of medication‐free subjects.     

Activation of working memory in patients at the earliest stage of multiple sclerosis—An fMRI study

Objective

Previous fMRI studies on activation of working memory in multiple sclerosis (MS) patients presented heterogeneous results. Patients were reported to have altered brain activation patterns either in typical working memory circuits or in other brain regions even if they did not have any cognitive impairment according to the test batteries. We hypothesized that brain activation patterns in patients at a very early stage of the disease at very low EDSS-Score would not differ from healthy subjects.

Methods

We examined 13 patients at an early stage of MS matched with 13 healthy controls with a detailed psychometric test battery and an fMRI working memory paradigm.

Results

Patients and healthy controls did not differ in psychometric test batteries. In both groups those cortex areas typically involved in working memory processes like dorso-lateral prefrontal (DLPFC), ventro-lateral-prefrontal (VLPFC), fronto-medial and parietal cortex areas (Brodmann 6, 7, 8, 9, 10, 32, 40, 45, 46, 47) were equally activated.

Conclusion

In contrast to former studies we found no differences in activation patterns in the fMRI scanning measuring working memory tasks between psychometrically tested homogenous groups of patients in early stages of MS and control subjects.     

fMRI study of language lateralization in children and adults

Language lateralization in the brain is dependent on family history of handedness, personal handedness, pathology, and other factors. The influence of age on language lateralization is not completely understood. Increasing left lateralization of language with age has been observed in children, while the reverse has been noted in healthy young adults. It is not known whether the trend of decreasing language lateralization with age continues in the late decades of life and at what age the inflection in language lateralization trend as a function of age occurs. In this study, we examined the effect of age on language lateralization in 170 healthy right-handed children and adults ages 5-67 using functional MRI (fMRI) and a verb generation task. Our findings indicate that language lateralization to the dominant hemisphere increases between the ages 5 and 20 years, plateaus between 20 and 25 years, and slowly decreases between 25 and 70 years.     

Information status and word order in Croatian Sign Language

This paper presents the results of research on information structure and word order in narrative sentences taken from signed short stories in Croatian Sign Language (HZJ). The basic word order in HZJ is SVO. Factors that result in other word orders include: reversible arguments, verb categories, locative constructions, contrastive focus, and prior context. Word order in context depends on communication rules, based on the relationship between old (theme) and new (rheme) information, which is predicated of the theme. In accordance with Grice's Maxim of Quantity, HZJ has a tendency to omit old information, or to reduce it to pronominal status. If old information is overtly signed in non‐pronominal form, it precedes the rheme. We have observed a variety of sign language mechanisms that are used to show items of reduced contextual significance: use of assigned spatial location for previously introduced referents; eyegaze to indicate spatial location of previously introduced referents; use of the non‐dominant hand for backgrounded information; use of a special category of signs known as classifiers as pronominal indicators of previously introduced referents; and complex noun phrases that allow a single occurrence of a noun to simultaneously serve multiple functions. These devices permit information to be conveyed without the need for separate signs for every referent, which would create longer constructions that could be taxing to both production and perception. The results of this research are compatible with well‐known word order generalizations—HZJ has its own grammar, independent of spoken language, like any other sign language.     

P3 amplitude attenuation secondary to increases in target-to-target interval (TTI) during spatial serial order recall: implications for EEG models of working memory function

Abstract

Research suggests that increasing delays in stimulus read-out can trigger declines in serial order recall accuracy due to increases in cognitive demand imposed by the delay; however, the exact neural mechanisms associated with this decline are unclear. Changes in neural resource allocation present as the ideal target and can easily be monitored by examining changes in the amplitude of an ERP component known as the P3. Changes in P3 amplitude secondary to exogenous pacing of stimulus read-out via increased target-to-target intervals (TTIs) during recall could reflect decreased neural resource allocation due to increased cognitive demand. This shift in resource allocation could result in working memory storage decay and the declines in serial order accuracy described by prior research. In order to examine this potential effect, participants were administered a spatial serial order processing task, with the recall series consisting of a series of correct (‘match’) or incorrect (‘non-match’ or ‘oddball’) stimuli. Moreover, the recall series included either a brief (500?ms) or extended (2000?ms) delay between stimuli. Results were significant for the presence of a P3 response to non-match stimuli for both experimental conditions, and attenuation of P3 amplitude secondary to the increase in TTI. These findings suggest that extending the delay between target recognition could increase cognitive demand and trigger a decrease in neural resource allocation that results in a decay of working memory stores.     

An fMRI study of verbal episodic memory encoding in amnestic mild cognitive impairment

Amnestic mild cognitive impairment (aMCI) is a high-risk and often prodromal state for the development of Alzheimer's disease (AD) and is characterised by isolated episodic memory impairment. Functional neuroimaging studies in healthy subjects consistently report left prefrontal cortex (PFC) activation during verbal episodic memory encoding. The PFC activation at encoding is related to semantic processing which enhances memory. The purpose of this study was to ascertain whether impaired verbal episodic memory in aMCI is related to PFC dysfunction. Using functional magnetic resonance imaging (fMRI) we compared 10 aMCI patients with 10 elderly controls during verbal encoding. The encoding task was sensitive to the effects of semantic processing. Subsequent recognition was tested to measure encoding success. Behavioural results revealed impaired recognition and a lower false recognition rate for semantically related distracters (lures) in aMCI, which suggest impaired semantic processing at encoding. Both groups activated left hemispheric PFC, insula, premotor cortex and cerebellum, but group comparisons revealed decreased activation in left ventrolateral PFC in the aMCI group. The magnitude of activation in left ventrolateral PFC during encoding was positively correlated with recognition accuracy in the control group but not in the aMCI group. We propose that verbal episodic memory impairment in aMCI is related to PFC dysfunction which affects semantic processing at encoding.     

Common deactivation patterns during working memory and visual attention tasks: an intra-subject fMRI study at 4 Tesla

This parametric functional magnetic resonance imaging (fMRI) study investigates the balance of negative and positive fMRI signals in the brain. A set of visual attention (VA) and working memory (WM) tasks with graded levels of difficulty was used to deactivate separate but overlapping networks that include the frontal, temporal, occipital, and limbic lobes; regions commonly associated with auditory and emotional processing. Brain activation (% signal change and volume) was larger for VA tasks than for WM tasks, but deactivation was larger for WM tasks. Load-related increases of blood oxygenation level-dependent (BOLD) responses for different levels of task difficulty cross-correlated strongly in the deactivated network during VA but less so during WM. The variability of the deactivated network across different cognitive tasks supports the hypothesis that global cerebral blood flow vary across different tasks, but not between different levels of task difficulty of the same task. The task-dependent balance of activation and deactivation might allow maximization of resources for the activated network.