Neural correlates of spatial working memory in humans: a functional magnetic resonance imaging study comparing visual and tactile processes

Recent studies of neural correlates of working memory components have identified both low-level perceptual processes and higher-order supramodal mechanisms through which sensory information can be integrated and manipulated. In addition to the primary sensory cortices, working memory relies on a widely distributed neural system of higher-order association areas that includes posterior parietal and occipital areas, and on prefrontal cortex for maintaining and manipulating information. The present study was designed to determine brain patterns of neural response to the same spatial working memory task presented either visually or in a tactile format, and to evaluate the relationship between spatial processing in the visual and tactile sensory modalities. Brain activity during visual and tactile spatial working memory tasks was measured in six young right-handed healthy male volunteers by using functional magnetic resonance imaging. Results indicated that similar fronto-parietal networks were recruited during spatial information processing across the two sensory modalities-specifically the posterior parietal cortex, the dorsolateral prefrontal cortex and the anterior cingulate cortex. These findings provide a neurobiological support to behavioral observations by indicating that common cerebral regions subserve generation of higher order mental representations involved in working memory independently from a specific sensory modality.     

Negative BOLD during tongue movement: A functional magnetic resonance imaging study

The aim of this functional magnetic resonance imaging (fMRI) study was to evaluate negative blood oxygen level-dependent (BOLD) signals during voluntary tongue movement. Deactivated (Negative BOLD) regions included the posterior parietal cortex (PPC), precuneus, and middle temporal gyrus. Activated (Positive BOLD) regions included the primary somatosensory-motor area (SMI), inferior parietal lobule, medial frontal gyrus, superior temporal gyrus, insula, lentiform nucleus, and thalamus. The results were not consistent with previous studies involving unilateral hand and finger movements showing the deactivation of motor-related cortical areas including the ipsilateral MI. The areas of Negative BOLD in the PPC and precuneus might reflect specific neural networks relating to voluntary tongue movement.     

Saccular stimulation of the human cortex: A functional magnetic resonance imaging study

Recent imaging studies have reported the projection of semicircular canal signals onto wide regions of the cerebral cortex but little is known about otolith projections onto the cerebral cortex. We used functional magnetic resonance imaging (fMRI) to investigate the activation of the cortex by loud clicks that selectively stimulate the sacculus. Twelve normal volunteers were presented with auditory stimuli via an earphone containing a piezo electric element. High-intensity [maximum volume of 120 dB (SPL)] or low-intensity [maximum volume of 110 dB (SPL)] clicks were delivered at a frequency of 1 Hz and lasted 1 ms. We first checked that the high-intensity, but not low-intensity, clicks stimulated the sacculus by determining the vestibular evoked myogenic potentials. We then analyzed two task conditions (high- and low-intensity clicks) in a boxcar paradigm. We obtained gradient echo echo-planar images by using a 1.5 T MRI system. We analyzed the fMRI time series data with SPM2. High-intensity clicks activated wide areas of the cortex, namely, the frontal lobe (prefrontal cortex, premotor cortex, and frontal eye fields), parietal lobe (the region around the intraparietal sulcus, temporo-parietal junction, and paracentral lobule), and cingulate cortex. These areas are similar to those reported in previous imaging studies that analyzed the cortical responses to the activation of the semicircular canals. Thus, semicircular canal and otolith/saccular signals may be processed in similar regions of the human cortex.     

功能磁共振在大脑皮质发育障碍患者的初步应用研究

目的：应用功能磁共振（fMRI）探讨6名正常受试者及2例皮质发育障碍（DCDs）患者在进行汉语词汇加工过程中脑激活模式，探讨DCDs患者与正常受试者之间脑激活区域的差异与临床意义。方法：本实验采用听觉刺激，以汉语单词理解为语言作业任务。结果：①正常受试者均出现显著的脑区激活，传统语言脑区Wemicke和Broca区激活在双侧大脑半球基本是对称的。除传统语言脑区激活外，还出现其它脑区激活现象。②两例DCDs患者表现为基本语言功能区的激活，诸如Wemicke区和Broca区激活。但脑激活表现为显著的不对称性，甚至完全偏侧性。结论：fMRI能够对大脑DCDs患者功能重塑皮质进行定位，为DCDs伴难治性癫痫患者手术治疗，避免损伤重要功能区提供了有益的保障。     

Neural activation during imitation of movements presented from four different perspectives: a functional magnetic resonance imaging study

The present study examined the effects of the perspective of movement presented for imitation in healthy volunteers, using functional magnetic resonance imaging (fMRI) to assess the magnitude and distribution of elicited brain activity. We sought to identify the pattern of brain activity associated with the performance of finger imitation tasks under four different imitation conditions. Video presentations of a hand and forearm performing random sequential contact between different fingers and the thumb were presented for imitation, while fMRI was recorded. The four types of model for imitation were: a hand and forearm pointing away from the subject, as if the subject were looking at their own limb (first-person perspective), from both anatomical (a right hand to be imitated by the subject's own right hand) and specular (a mirror image or “left” hand to be imitated by the subject's right hand) perspectives; and a hand/forearm pointing toward the subject, as if it was the hand of another person facing the subject (third-person perspective), from both anatomical (the opposite person's right hand) and specular (the opposite person's left hand) perspectives. In addition, participants completed a motor control task. The results revealed a significant difference in the magnitude of brain activation between the first- and third-person perspective conditions, suggesting that subjects used the first-person imitation model as a substitute for internal self-representation, thus requiring less effort. The first-person perspective anatomical model activated only the right posterior insula, recruiting significantly fewer brain regions than the other model types, compared with the control condition. These findings suggest that first-person anatomical perspective models may be optimal for ease of imitation in motor learning.     

The human amygdala is involved in general behavioral relevance detection: evidence from an event-related functional magnetic resonance imaging Go-NoGo task

The amygdala is classically regarded as a detector of potential threat and as a critical component of the neural circuitry mediating conditioned fear responses. However, it has been reported that the human amygdala responds to multiple expressions of emotions as well as emotionally neutral stimuli of a novel, uncertain or ambiguous nature. Thus, it has been proposed that the function of the amygdala may be of a more general art, i.e. as a detector of behaviorally relevant stimuli [Sander D, Grafman J, Zalla T (2003) The human amygdala: an evolved system for relevance detection. Rev Neurosci 14:303-316]. To investigate this putative function of the amygdala, we used event related functional magnetic resonance imaging (fMRI) and a modified Go-NoGo task composed of behaviorally relevant and irrelevant letter and number stimuli. Analyses revealed bilateral amygdala activation in response to letter stimuli that were behaviorally relevant as compared with letters with less behavioral relevance. Similar results were obtained for relatively infrequent NoGo relevant stimuli as compared with more frequent Go stimuli. Our findings support a role for the human amygdala in general detection of behaviorally relevant stimuli.     

Pattern of cortical reorganization in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study

Depending on individual lesion location and extent, reorganization of the human motor system has been observed with a high interindividual variability. In addition, variability of forces exerted, of motor effort, and of movement strategies complicates the interpretation of functional imaging studies. We hypothesize that a general pattern of reorganization can be identified if a homogeneous patient population is chosen and experimental conditions are controlled. Patients with amyotrophic lateral sclerosis (ALS) and healthy volunteers were trained to perform a simple finger flexion task with 10% of each individual's maximum grip force with constant movement amplitude and frequency. The activation pattern in ALS patients was distinctly different to that in healthy controls: In ALS patients, motor cortex activation was located more anteriorly, encompassing the premotor gyrus. The cluster volume within the supplementary motor area (SMA) was higher and shifted toward the pre-SMA. Contralateral inferior area 6 and bilateral parietal area 40 revealed higher cluster volumes. Our results demonstrate a general pattern of functional changes after motor neuron degeneration. They support the concept of a structurally parallel and functionally specialized organization of voluntary motor control. Degeneration of the first and second motor neurons leads to enhanced recruitment of motor areas usually involved in initiation and planning of movement. Partial compensation between functionally related motor areas seems to be a strategy to optimize performance if the most efficient pathway is unavailable.     

Cardiovascular risks and brain function: a functional magnetic resonance imaging study of executive function in older adults

Cardiovascular (CV) risk factors, such as hypertension, diabetes, and hyperlipidemia are associated with cognitive impairment and risk of dementia in older adults. However, the mechanisms linking them are not clear. This study aims to investigate the association between aggregate CV risk, assessed by the Framingham general cardiovascular risk profile, and functional brain activation in a group of community-dwelling older adults. Sixty participants (mean age: 64.6 years) from the Brain Health Study, a nested study of the Baltimore Experience Corps Trial, underwent functional magnetic resonance imaging using the Flanker task. We found that participants with higher CV risk had greater task-related activation in the left inferior parietal region, and this increased activation was associated with poorer task performance. Our results provide insights into the neural systems underlying the relationship between CV risk and executive function. Increased activation of the inferior parietal region may offer a pathway through which CV risk increases risk for cognitive impairment.     

特殊感觉障碍人群(盲人)脑功能磁共振成像研究

目的：探讨特殊感觉障碍人群(盲人)大脑枕叶视皮层及相关结构在肓文阅读时充当的角色。方法：采用功能磁共振成像(fMRI)技术研究8名先天和后天盲人，在刺激(触摸中国盲文)和静止等两种对比条件下采集枕叶和有关皮层的回波平面图象。结果：盲人阅读中国盲文时在距状裂附近的纹状区、纹外区包括次级视觉中枢及与视觉信息处理有关的脑区均有激活信号出现，而正常人触摸盲文时上述脑区未出现明显激活信号。结论：枕叶可能参与肓文阅读过程的触觉信息识别：     

Neural correlates of internally-generated disgust via autobiographical recall: a functional magnetic resonance imaging investigation

Converging lines of evidence suggest the involvement of the insula and basal ganglia in the processing of disgust, an important primary emotion that guides the avoidance of potential physical contamination and disease. Prior human lesion and functional brain imaging studies have employed exteroceptive sensory stimuli such as facial expressions of disgust, and disgust-eliciting pictures. Thus, the neural substrates underlying the internal experience of disgust remain unknown. The present fMRI study examined the neural correlates of self-induced disgust aided by the recall and re-experience of personally salient life events. Subjects were scanned while they recalled and re-experienced either a recent situation that evoked intense disgust or a time-matched, equally vivid neutral/non-emotional event. Relative to the emotionally neutral condition, self-induced disgust was associated with activation of the insula, hippocampus, anterior and posterior cingulate cortex, basal ganglia, thalamus, and primary visual cortex. These findings suggest that areas previously associated with the perception of disgust (e.g., insula, basal ganglia) are also involved interoceptive experience of disgust.     

Neuronal correlates of encoding and retrieval in episodic memory during a paired-word association learning task: a functional magnetic resonance imaging study

The investigation of memory function using functional magnetic resonance imaging (fMRI) is an expanding field of research. The aim of this study was to demonstrate brain-activity patterns related to a word-pair association task employing a whole-brain EPI sequence. Six right-handed, healthy male volunteers (mean age: 27.5 years) took part in the study. fMRI was performed at a field strength of 1.5 Tesla with 26–32 slices parallel to the AC-PC line, depending on individual brain size. Distributed brain regions were activated in episodic encoding and retrieval with similarities, but also (distinct) differences in activation patterns. Bilateral prefrontal cortical areas were involved when comparing encoding as well as retrieval to the reference condition (nonsense words). Furthermore, activation was observed in cerebellar areas during encoding, and activation in bilateral parietal areas (precuneus and inferior parietal cortex) was differentially more pronounced during retrieval. The activation of left dorsomedial thalamus during retrieval of high imagery-content word-pair associates may point to the role of this structure in episodic retrieval. The direct cognitive subtraction of encoding minus retrieval yielded a differentially larger left prefrontal activation. There was a differentially higher right prefrontal activation during retrieval than during encoding, underlining the proposed right/left asymmetry for episodic memory processes. Received: 10 June 1998 / Accepted: 23 April 1999     

Neural correlates of conceptual object priming in young and older adults: an event-related functional magnetic resonance imaging study

In this event-related functional magnetic resonance imaging study, we investigated age-related differences in brain activity associated with conceptual repetition priming in young and older adults. Participants performed a speeded “living/nonliving” classification task with 3 repetitions of familiar objects. Both young and older adults showed a similar magnitude of behavioral priming to repeated objects and evidenced repetition-related activation reductions in fusiform gyrus, superior occipital, middle, and inferior temporal cortex, and inferior frontal and insula regions. The neural priming effect in young adults was extensive and continued through both the second and third stimulus repetitions, and neural priming in older adults was markedly attenuated and reached floor at the second repetition. In young adults, greater neural priming in multiple brain regions correlated with greater behavioral facilitation and in older adults, only activation reduction in the left inferior frontal correlated with faster behavioral responses. These findings provide evidence for altered neural priming in older adults despite preserved behavioral priming, and suggest the possibility that age-invariant behavioral priming is observed as a result of more sustained neural processing of stimuli in older adults which might be a form of compensatory neural activity.     

A functional magnetic resonance imaging navigated repetitive transcranial magnetic stimulation study of the posterior parietal cortex in normal pain and hyperalgesia

Noxious stimuli activate a complex cerebral network. During central sensitization to pain, activity in most of these areas is changed. One of these areas is the posterior parietal cortex (PPC). The role of the PPC during processing of acute pain as well as hyperalgesia and tactile allodynia remains elusive. Therefore, we performed a functional magnetic resonance imaging (fMRI) based, neuro-navigated, repetitive transcranial magnetic stimulation (rTMS) study in 10 healthy volunteers. Firstly, pin-prick hyperalgesia was provoked on the right volar forearm, using the model of electrically-induced secondary mechanical hyperalgesia. fMRI was performed during pin-prick stimulation inside and outside the hyperalgesic areas. Secondly, on four different experimental sessions, the left and right individual intraparietal BOLD peak-activations were used as targets for a sham-controlled 1 Hz rTMS paradigm of 10 min duration. We measured psychophysically the (i) electrical pain stimulus intensity on an 11-point numeric pain rating scale (NRS, 0–10), the (ii) area of hyperalgesia, and the (iii) area of dynamic mechanical allodynia. Sham stimulation or rTMS was performed 16 min after induction of pin-prick hyperalgesia and tactile allodynia. Compared to sham stimulation, no significant effect of rTMS was observed on pain stimulus intensity and the area of allodynia. However, a reduction of the hyperalgesic area was observed for rTMS of the left PPC (P<0.05). We discuss the role of the PPC in central sensitization to pain, in spatial discrimination of pain stimuli and in spatial-attention to pain stimuli.     

Changes in resting connectivity with age: a simultaneous electroencephalogram and functional magnetic resonance imaging investigation

Resting fluctuations in the blood oxygenation level-dependent signal have attracted considerable interest for their sensitivity to pathological brain processes. However, these analyses are susceptible to confound by nonneural physiological factors such as vasculature, breathing, and head movement which is a concern when investigating elderly or pathological groups. Here, we used simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) (EEG/fMRI) to constrain the analysis of resting state networks (RSNs) and identify aging differences. Four of 26 RSNs showed fMRI and EEG/fMRI group differences; anterior default-mode network, left frontal-parietal network, bilateral middle frontal, and postcentral gyri. Seven RSNs showed only EEG/fMRI differences suggesting the combination of these 2 methods might be more sensitive to age-related neural changes than fMRI alone. Five RSNs showed only fMRI differences and might reflect nonneural group differences. Activity within some EEG/fMRI RSNs was better explained by neuropsychological measures (Mini Mental State Examination and Stroop) than age. These results support previous studies suggesting that age-related changes in specific RSNs are neural in origin, and show that changes in some RSNs relate better to elderly cognition than age.     

Figural memory performance and functional magnetic resonance imaging activity across the adult lifespan

We examined performance and functional magnetic resonance imaging activity in participants (n = 235) aged 17–81 years on a nonverbal recognition memory task, figural memory. Reaction time, error rate, and response bias measures indicated that the youngest and oldest participants were faster, made fewer errors, and showed a more conservative response bias than participants in the median age ranges. Encoding and Recognition phases activated a distributed bilateral network encompassing prefrontal, subcortical, lateral, and medial temporal and occipital regions. Activation during Encoding phase did not correlate with age. During Recognition, task-related activation for correctly identified targets (Hit-Targets) correlated linearly positively with age; nontask related activity correlated negative quadratically with age. During correctly identified distractors (Hit-Distractors) activity in task-related regions correlated positive linearly with age, nontask activity showed positive and negative quadratic relationships with age. Missed-Targets activity did not correlate with age. We concluded that figural memory performance and functional magnetic resonance imaging activity during Recognition but not Encoding was affected both by continued maturation of the brain in the early 20s and compensatory recruitment of additional brain regions during recognition memory in old age.     

Sleep and resting‐state functional magnetic resonance imaging connectivity in middle‐aged adults and the elderly: A population‐based study

Sleep problems increase with ageing. Increasing evidence suggests that sleep problems are not only a consequence of age‐related processes, but may independently contribute to developing vascular or neurodegenerative brain disease. Yet, it remains unclear what mechanisms underlie the impact sleep problems may have on brain health in the general middle‐aged and elderly population. Here, we studied sleep's relation to brain functioning in 621 participants (median age 62 years, 55% women) from the population‐based Rotterdam Study. We investigated cross‐sectional associations of polysomnographic and subjectively measured aspects of sleep with intrinsic neural activity measured with resting‐state functional magnetic resonance imaging on a different day. We investigated both functional connectivity between regions and brain activity (blood‐oxygen‐level‐dependent signal amplitude) within regions, hierarchically towards smaller topographical levels. We found that longer polysomnographic total sleep time is associated with lower blood‐oxygen‐level‐dependent signal amplitude in (pre)frontal regions. No objective or subjective sleep parameters were associated with functional connectivity between or within resting‐state networks. The findings may indicate a pathway through which sleep, in a ‘real‐life’ population setting, impacts brain activity or regional brain activity determines total sleep time.     

Sleep stabilizes visuomotor adaptation memory: a functional magnetic resonance imaging study

The beneficial effect of sleep on motor memory consolidation is well known for motor sequence memory, but remains unsettled for visuomotor adaptation in humans. The aim of this study was to characterize more clearly the influence of sleep on consolidation of visuomotor adaptation using a between‐subjects functional magnetic resonance imaging (fMRI) design contrasting sleep to total sleep deprivation. Our behavioural results, based on seven different parameters, show that sleep stabilizes performance whereas sleep deprivation deteriorates it. During training, while a set of cerebellar, striatal and cortical areas is activated in proportion to performance improvement, the recruitment of the hippocampus and frontal cortex protects motor memory against the detrimental effects of sleep deprivation. During retest after sleep loss a cerebello–cortical network, usually involved in the earliest stage of learning, was recruited to perform the task. In contrast, no changes in cerebral activity were observed after sleep, suggesting that it may only support the stabilization of the visuomotor adaptation memory trace.     

Assessing the working memory network: studies with functional magnetic resonance imaging and structural equation modeling

A considerable body of evidence supports the notion that the neurofunctional substrate of working memory is not only related to the integrity of the prefrontal cortex, but also to the concerted interplay of widespread interacting networks including the parietal cortex, subcortical regions and cerebellar areas. Modern functional brain imaging techniques such as functional magnetic resonance imaging (fMRI) have provided a detailed picture of functional neuroanatomy subserving working memory functions. Most of the earlier functional studies were directed toward the identification of brain areas subserving specific cognitive domains in terms of a functional segregation. More recently, different multivariate techniques were employed to specifically address measures of functional or effective connectivity. Structural equation modeling (SEM) or path analysis is one of the most often used methods to model interactions among covarying brain areas in an explicitly model-based approach. The present review will focus on basic methodological issues of SEM for the analysis of fMRI datasets in studies of working memory. Aside from a discussion of previous studies and their essential findings, advanced methodological issues and caveats as well as future perspectives of the method will be addressed.     

Neural mechanisms of Korean word reading: a functional magnetic resonance imaging study

The use of functional magnetic resonance imaging permits the collection of brain activation patterns when native Korean speakers (12 persons as subjects) read Korean words and Chinese characters. The Korean language uses both alphabetic Korean words and logographic Chinese characters in its writing system. Our experimental results show that the activation patterns obtained for reading Chinese characters by Korean native speakers involve neural mechanisms that are similar to Chinese native speakers; i.e. strong left-lateralized middle frontal cortex activation. For the case of Korean word reading, the activation pattern in the bilateral fusiform gyrus, left middle frontal gyrus, left superior temporal gyrus, right mid temporal gyrus, precentral gyrus, and insula was observed. This suggests that the activation pattern for Korean word reading appears to corroborate with that of alphabetic words at the general level. A further noteworthy finding of our study is the strong activation of the posterior part of the right dorsolateral prefrontal cortex (BA 8). The right hemispheric BA 8 belongs to the visual higher order control area and we propose that this area should be responsible for processing of visuospatial (surface form) information of Korean words.     

Ventrolateral prefrontal cortex activity associated with individual differences in arbitrary delayed paired-association learning performance: A functional magnetic resonance imaging study

To describe the neural substrates of successful episodic long-term memory encoding, we collected functional magnetic-resonance imaging data as participants completed an arbitrary delayed auditory paired-association learning task. During the task, subjects learned predefined but hidden stimulus pairs by trial and error based on visual feedback. Delay period activity represents the retrieval of the relationship between the cue item and its candidate for associates, that is, working memory. Our hypothesis was that the neural substrates of working memory would be related to long-term memory encoding in a performance-dependent manner. Thus, inter-individual variance in performance following a fixed learning set would be associated with differing neural activations during the delay period. The number of learning trials was adjusted such that performance following completion of the learning set varied across subjects. Each trial consisted of the successive presentation of two stimuli (first stimulus and second stimulus [S2]) with a fixed delay interval, allowing extraction of sustained activity during the delay period. Sustained activities during the delay period were found in the bilateral dorsolateral prefrontal cortex, intraparietal sulcus, and left ventrolateral prefrontal cortex, as well as the premotor and pre-supplementary motor areas. The activities did not change in strength across learning, suggesting that these effects represent working memory components. The sustained activity in the ventrolateral prefrontal region was correlated with task performance. Task performance was also positively correlated with the decrement in S2/feedback-related activity during learning in the superior temporal sulcus, a region previously shown to be involved in association learning. These findings are consistent with lesion and neuroimaging studies showing that the ventrolateral prefrontal cortex plays an important role in long-term memory encoding, and raise the possibility that working memory processes interact with long-term memory formation as represented by the covariation of activity in the superior temporal sulcus and the ventrolateral prefrontal cortex.