Dissociation of mnemonic and perceptual processes during spatial and nonspatial working memory using fMRI

Neuroimaging studies in humans have consistently found robust activation of frontal, parietal, and temporal regions during working memory tasks. Whether these activations represent functional networks segregated by perceptual domain is still at issue. Two functional magnetic resonance imaging experiments were conducted, both of which used multiple-cycle, alternating task designs. Experiment 1 compared spatial and object working memory tasks to identify cortical regions differentially activated by these perceptual domains. Experiment 2 compared working memory and perceptual control tasks within each of the spatial and object domains to determine whether the regions identified in experiment 1 were driven primarily by the perceptual or mnemonic demands of the tasks, and to identify common brain regions activated by working memory in both perceptual domains. Domain-specific activation occurred in the inferior parietal cortex for spatial tasks, and in the inferior occipitotemporal cortex for object tasks, particularly in the left hemisphere. However, neither area was strongly influenced by task demands, being nearly equally activated by the working memory and perceptual control tasks. In contrast, activation of the dorsolateral prefrontal cortex and the intraparietal sulcus (IPS) was strongly task-related. Spatial working memory primarily activated the right middle frontal gyrus (MFG) and the IPS. Object working memory activated the MFG bilaterally, the left inferior frontal gyrus, and the IPS, particularly in the left hemisphere. Finally, activation of midline posterior regions, including the cingulate gyrus, occurred at the offset of the working memory tasks, particularly the shape task. These results support a prominent role of the prefrontal and parietal cortices in working memory, and indicate that spatial and object working memory tasks recruit differential hemispheric networks. The results also affirm the distinction between spatial and object perceptual processing in dorsal and ventral visual pathways. Hum. Brain Mapping 6:14–32, 1998. © 1998 Wiley-Liss, Inc.     

Modulation of alpha and gamma oscillations related to retrospectively orienting attention within working memory

Selective attention mechanisms allow us to focus on information that is relevant to the current behavior and, equally important, ignore irrelevant information. An influential model proposes that oscillatory neural activity in the alpha band serves as an active functional inhibitory mechanism. Recent studies have shown that, in the same way that attention can be selectively oriented to bias sensory processing in favor of relevant stimuli in perceptual tasks, it is also possible to retrospectively orient attention to internal representations held in working memory. However, these studies have not explored the associated oscillatory phenomena. In the current study, we analysed the patterns of neural oscillatory activity recorded with magnetoencephalography while participants performed a change detection task, in which a spatial retro‐cue was presented during the maintenance period, indicating which item or items were relevant for subsequent retrieval. Participants benefited from retro‐cues in terms of accuracy and reaction time. Retro‐cues also modulated oscillatory activity in the alpha and gamma frequency bands. We observed greater alpha activity in a ventral visual region ipsilateral to the attended hemifield, thus supporting its suppressive role, i.e. a functional disengagement of task‐irrelevant regions. Accompanying this modulation, we found an increase in gamma activity contralateral to the attended hemifield, which could reflect attentional orienting and selective processing. These findings suggest that the oscillatory mechanisms underlying attentional orienting to representations held in working memory are similar to those engaged when attention is oriented in the perceptual space.     

Numerical working memory alters alpha‐beta oscillations and connectivity in the parietal cortices

Although the neural bases of numerical processing and memory have been extensively studied, much remains to be elucidated concerning the spectral and temporal dynamics surrounding these important cognitive processes. To further this understanding, we employed a novel numerical working memory paradigm in 28 young, healthy adults who underwent magnetoencephalography (MEG). The resulting data were examined in the time‐frequency domain prior to image reconstruction using a beamformer. Whole‐brain, spectrally‐constrained coherence was also employed to determine network connectivity. In response to the numerical task, participants exhibited robust alpha/beta oscillations in the bilateral parietal cortices. Whole‐brain statistical comparisons examining the effect of numerical manipulation during memory‐item maintenance revealed a difference centered in the right superior parietal cortex, such that oscillatory responses during numerical manipulation were significantly stronger than when no manipulation was necessary. Additionally, there was significantly reduced cortico‐cortical coherence between the right and left superior parietal regions during the manipulation compared to the maintenance trials, indicating that these regions were functioning more independently when the numerical information had to be actively processed. In sum, these results support previous studies that have implicated the importance of parietal regions in numerical processing, but also provide new knowledge on the spectral, temporal, and network dynamics that serve this critical cognitive function during active working memory maintenance.     

Somatosensory working memory performance in humans depends on both engagement and disengagement of regions in a distributed network

Successful working memory (WM) requires the engagement of relevant brain areas but possibly also the disengagement of irrelevant areas. We used magnetoencephalography (MEG) to elucidate the temporal dynamics of areas involved in a somatosensory WM task. We found an increase in gamma band activity in the primary and secondary somatosensory areas during encoding and retention, respectively. This was accompanied by an increase of alpha band activity over task‐irrelevant regions including posterior and ipsilateral somatosensory cortex. Importantly, the alpha band increase was strongest during successful WM performance. Furthermore, we found frontal gamma band activity that correlated both with behavioral performance and the alpha band increase. We suggest that somatosensory gamma band activity reflects maintenance and attention‐related components of WM operations, whereas alpha band activity reflects frontally controlled disengagement of task‐irrelevant regions. Our results demonstrate that resource allocation involving the engagement of task‐relevant and disengagement of task‐irrelevant regions is needed for optimal task execution. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Relationship between prefrontal task-related activity and information flow during spatial working memory performance

While monkeys performed spatial working memory tasks, cue- (C), delay- (D), and response-period (R) activities or their combinations (CD, CR, DR, CDR) were observed in prefrontal neurons. In the present study, we tried to understand information flow during spatial working memory performances and how each task-related neuron contributed to this process. We first characterized each neuron based on which task-related activity was exhibited and which information (cue location or saccade direction) each task-related activity represented, then classified these neurons into 9 groups (C, Dcue, Dsac, CDcue, DcueRcue, DsacRsac, DcueRsac, CDcueRcue and CDcueRsac). Preferred directions were similar between cue- and delay-period activities in CDcue, CDcueRcue, and CDcueRsac, indicating that the directional selectivity of delay-period activity is affected by the directional selectivity of cue-period activity, all of which represented visual information. Preferred directions were also similar between delay- and response-period activities in DcueRcue, CDcueRcue, and DsacRsac, indicating that the directional selectivity of delay-period activity affects the directional selectivity of response-period activity in these neurons. By the comparison of temporal profiles of delay-period activity among these groups, we found (1) cue-period activity could affect directional selectivity of delay-period activity of CDcue and CDcueRcue, (2) cue-period activity of C, CDcue, and CDcueRcue might contribute to the initiation and the maintenance of delay-period activity of CDcue, CDcueRcue, Dcue, and DcueRcue, and (3) saccade-related activity of DsacRsac could be affected by delay-period activity of Dsac and DsacRsac. These results suggest that the combination of task-related activities, the information represented by each activity, and the temporal profile of delay-period activity are important factors to consider information flow and processing and integration of the information in the prefrontal cortex during spatial working memory processes.     

Dissociation between MEG alpha modulation and performance accuracy on visual working memory task in obsessive compulsive disorder

Oscillatory brain activity in the alpha band (8-13 Hz) is modulated by cognitive events. Such modulation is reflected in a decrease of alpha (event-related desynchronization; ERD) with high cognitive load, or an increase (event-related synchronization) with low cognitive demand or with active inhibition of distractors. We used magnetoencephalography to investigate the pattern of prefrontal and parieto-occipital alpha modulation related to two variants of visual working memory task (delayed matching-to-sample) with and without a distractor. We tested nonmedicated, nondepressed patients suffering obsessive-compulsive disorder (OCD), and pair-matched healthy controls. The level of event-related alpha as a function of time was estimated using the temporal-spectral evolution technique. The results in OCD patients indicated: (1) a lower level of prestimulus (reference) alpha when compared to controls, (2) a task-phase specific reduction in event-related alpha ERD in particular for delayed matching-to-sample task with distractor, (3) no significant correlations between the pattern of modulation in prefrontal and parietal-occipital alpha oscillatory activity. Despite showing an abnormally low alpha modulation, the OCD patients' performance accuracy was normal. The results suggest a relationship of alpha oscillations and the underlying thalamocortical network to etiology of OCD and an involvement of a compensatory mechanism related to effortful inhibition of extrinsic and intrinsic interference.     

Masking effects on subjective annoyance to aircraft flyover noise: An fMRI study

Sound masking, a new noise control technology, has been applied to improve subjective perception of noise in recent years. However, the neural mechanisms underlying this technology are still unclear. In this study, 18 healthy subjects were recurited to take subjective annoyance assessments and fMRI scanning with the aircraft noise and the masked aircraft noise. The results showed that the noise annoyance was associated with deficient functional connectivity between anterior cingulate cortex (ACC) and prefrontal cortex and exceeded brain activation in ACC, which might be explained as compensation. The sound masking led to significantly strong activation in the left medial frontal cortex and right medial orbital frontal cortex, which were associated with happy emotion induced by sound masking. This study offered new insights on the underlying neural mechanisms of sound masking effects.     

EEG alpha synchronization and functional coupling during top-down processing in a working memory task

Electroencephalogram (EEG) alpha (around 10 Hz) is the dominant rhythm in the human brain during conditions of mental inactivity. High amplitudes as observed during rest usually diminish during cognitive effort. During retention of information in working memory, however, power increase of alpha oscillations can be observed. This alpha synchronization has been interpreted as cortical idling or active inhibition. The present study provides evidence that during top-down processing in a working memory task, alpha power increases at prefrontal but decreases at occipital electrode sites, thereby reaching a state in which alpha power and frequency become very similar over large distances. Two experimental conditions were compared. In the first, visuospatial information only had to be retained in memory whereas the second condition additionally demanded manipulation of the information. During the second condition, stronger alpha synchronization at prefrontal sites and larger occipital alpha suppression was observed as compared to that for pure retention. This effect was accompanied by assimilation of prefrontal and occipital alpha frequency, stronger functional coupling between prefrontal and occipital brain areas, and alpha latency shifts from prefrontal cortex to primary visual areas, possibly indicating the control of posterior cortical activation by anterior brain areas. An increase of prefrontal EEG alpha amplitudes, which is accompanied by a decrease at posterior sites, thus may not be interpreted in terms of idling or "global" inhibition but may enable a tight functional coupling between prefrontal cortical areas, and thereby allows the control of the execution of processes in primary visual brain regions.     

Aging effects on regional brain structural changes in schizophrenia

Background: Although mostly conceptualized as a neurodevelopmental disorder, there is an increasing interest in progressive changes of cognitive deficits and brain structure and function in schizophrenia across the life span.Methods: In this study, we investigated age-related changes in regional gray matter using voxel-based morphometry in a sample of 99 patients (age range 18–65 years) with Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia and 113 healthy controls (age range 19–59 years) using a cross-sectional design.Results: We found steeper age-related decline in gray matter in patients in a cluster comprising the left superior temporal cortex and adjacent inferior parietal lobule. We then divided the schizophrenia sample in 3 subgroups based on a 3-factor model of psychopathology ratings. Age-related changes were markedly different in each of the 3 subgroups (compared with healthy controls). While patients with predominantly paranoid symptoms showed stronger age-related progression in the left superior temporal cortex and right inferior frontal gyrus, those of the disorganized subgroup had stronger gray matter loss in the left lateral cerebellum, while the predominantly negative subgroup showed minor effects in the left superior temporal gyrus.Conclusions: Our findings show that differences in brain structural changes associated with aging diverge between schizophrenia patients and healthy subjects and that different subgroups within a patient sample might be at higher risk of age-related regional gray matter loss.     

Lateralized contribution of prefrontal cortex in controlling task-irrelevant information during verbal and spatial working memory tasks: rTMS evidence

The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. The present study used repetitive transcranial magnetic stimulation (rTMS) to clarify the role of the dorsolateral prefrontal cortex (dlPFC) both in the types of information (verbal vs. spatial), and the types of processes (maintenance vs. manipulation). Subjects performed three independent experiments (1-back and 2-back tasks) while rTMS was applied over dlPFC for 500 ms in the last period of the delay. In two experiments (1 and 2) physically identical stimuli (letters shown at different locations on a screen) under different domain conditions (letters or locations) were employed. Under these conditions, we discovered a double dissociation only in the 2-back task: during the letter condition, when applied to the right dlPFC, rTMS significantly delayed task performance, whereas, the same result was present during the location condition, but only when rTMS was applied to the left dlPFC. The other 2-back task (experiment 3), in which we had eliminated the task-irrelevant information (i.e. we used stimuli that varied only in one domain), did not show significant results. We propose that the functional dichotomy of the hemispheres may be due to mechanisms of cognitive control on interference, which resolve conflict through the inhibition of task-irrelevant information only during high WM load. In conclusion, these findings confirm the role of dlPFC in implementing top-down attentional control, and provide evidence for the theoretical suggestion that working memory serves to control selective attention in the normal human brain.     

Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS‐EEG and working memory performance

Intermittent theta burst stimulation (iTBS) is a noninvasive brain stimulation technique capable of increasing cortical excitability beyond the stimulation period. Due to the rapid induction of modulatory effects, prefrontal application of iTBS is gaining popularity as a therapeutic tool for psychiatric disorders such as depression. In an attempt to increase efficacy, higher than conventional intensities are currently being applied. The assumption that this increases neuromodulatory may be mechanistically false for iTBS. This study examined the influence of intensity on the neurophysiological and behavioural effects of iTBS in the prefrontal cortex. Sixteen healthy participants received iTBS over prefrontal cortex at either 50, 75 or 100% resting motor threshold in separate sessions. Single‐pulse TMS and concurrent electroencephalography (EEG) was used to assess changes in cortical reactivity measured as TMS‐evoked potentials and oscillations. The n‐back task was used to assess changes in working memory performance. The data can be summarised as an inverse U‐shape relationship between intensity and iTBS plastic effects, where 75% iTBS yielded the largest neurophysiological changes. Improvement in reaction time in the 3‐back task was supported by the change in alpha power, however, comparison between conditions revealed no significant differences. The assumption that higher intensity results in greater neuromodulatory effects may be false, at least in healthy individuals, and should be carefully considered for clinical populations. Neurophysiological changes associated with working memory following iTBS suggest functional relevance. However, the effects of different intensities on behavioural performance remain elusive in the present healthy sample.     

Time course of superior temporal sulcus activity in response to eye gaze: a combined fMRI and MEG study

The human superior temporal sulcus (STS) has been suggested to be involved in gaze processing, but temporal data regarding this issue are lacking. We investigated this topic by combining fMRI and MEG in four normal subjects. Photographs of faces with either averted or straight eye gazes were presented and subjects passively viewed the stimuli. First, we analyzed the brain areas involved using fMRI. A group analysis revealed activation of the STS for averted compared to straight gazes, which was confirmed in all subjects. We then measured brain activity using MEG, and conducted a 3D spatial filter analysis. The STS showed higher activity in response to averted versus straight gazes during the 150–200 ms period, peaking at around 170 ms, after stimulus onset. In contrast, the fusiform gyrus, which was detected by the main effect of stimulus presentations in fMRI analysis, exhibited comparable activity across straight and averted gazes at about 170 ms. These results indicate involvement of the human STS in rapid processing of the eye gaze of another individual.     

Elevated body mass in National Football League players linked to cognitive impairment and decreased prefrontal cortex and temporal pole activity

Obesity is a risk factor for neurodegenerative disease and has been shown to adversely affect cognitive function. Professional athletes who participate in sports, which expose them to repetitive concussions, may be at heightened risk for cognitive impairment. Here, we investigated the effects of body mass as measured by waist-to-height ratio (WHtR) on regional cerebral blood flow using single-photon emission computed tomography imaging in 38 healthy weight (WHtR mean 49.34±2.8; age 58±9.6) and 38 overweight (WHtR mean 58.7±4.7; age 58±13.3) retired National Football League football players. After matching for age and position, we used a two sample t-test to determine the differences in blood flow in healthy versus overweight subjects. Statistical parametric mapping revealed a higher WHtR ratio is associated with decreased blood flow in Brodmann areas 8, 9 and 10, brain regions involved in attention, reasoning and executive function (P<0.05, family-wise error) along with deficits in the temporal pole. Moreover, overweight athletes had significant decrease in attention (P=0.01326), general cognitive proficiency (P=0.012; Microcog: Assessment of Cognitive Functioning) and memory (P=0.005; Mild Cognitive Impairment Screen). The association between elevated WHtR percentage and decreased blood flow in the prefrontal cortex and temporal pole may be correlated with the decreased performance on tests of attention and memory. These findings suggest that a weight management program may be critical to the health of athletes who have been exposed to mild brain trauma during their careers.     

Revisiting Geschwind's hypothesis on brain lateralisation: A functional MRI study of digit ratio (2D:4D) and sex interaction effects on spatial working memory

The Geschwind-Behan-Galaburda (GBG) hypothesis links cerebral lateralisation with prenatal testosterone exposure. Digit ratio measures in adults have been established as potential markers of foetal sex hormonal milieu. The aim of the study was to evaluate the sex-dependent interaction of digit ratio measures and cerebral lateralization as well as their neurohemodynamic correlates using functional MRI (fMRI). Digit ratio measures—ratio of index finger (2D) length to ring finger (4D) length (2D:4D) and difference between 2D:4D of two hands, i.e., right minus left (D_R–L)—were calculated using high resolution digital images in 70 right-handed participants (42 men) based on reliable and valid method. fMRI was acquired during the performance of a spatial working memory task in a subset of 25 individuals (14 men), and analysed using Statistical Parametric Mapping 8 (SPM8) and the Laterality Index toolbox for SPM8. Men had significantly less bilateral 2D:4D than women. There was a significant negative correlation between right 2D:4D and 2-Back task accuracy (2B_ACC) in women. A significant sex-by-right 2D:4D interaction was observed in left parahippocampal gyrus activation. Additionally, sex-by-D_R–L interaction was observed in left IPL activation. D_R–L showed a significant positive correlation with the whole brain Laterality Index (LI), and LI, in turn, demonstrated a significant negative correlation with 2B_ACC. Our study observations suggest several novel sex-differential relationships between 2D:4D measures and fMRI activation during spatial working memory task performance. Given the pre-existing background data supporting digit ratio measures as putative indicator of prenatal sex hormonal milieu, our study findings add support to the Geschwind-Behan-Galaburda (GBG) hypothesis.     

Measuring alterations in oscillatory brain networks in schizophrenia with resting-state MEG: State-of-the-art and methodological challenges

Objective

Neuroimaging studies provide evidence of disturbed resting-state brain networks in Schizophrenia (SZ). However, untangling the neuronal mechanisms that subserve these baseline alterations requires measurement of their electrophysiological underpinnings. This systematic review specifically investigates the contributions of resting-state Magnetoencephalography (MEG) in elucidating abnormal neural organization in SZ patients.

Neural structures and mechanisms involved in scene recognition: a review and interpretation

Since the discovery in 1996 that a region within caudal parahippocampal cortex subserves learning and recall of topographical information, numerous studies aimed at elucidating the structures and pathways involved in scene recognition have been published. Neuroimaging studies, in particular, have revealed the locations and identities of some of the principal cortical structures that mediate these faculties. In the present study the detailed organization of the system is examined, based on a meta-analysis of neuroimaging studies of scene processing in human subjects, combined with reviews of the results of lesions on this type of processing, single neuron studies, and available hodological data in non-human primates. A cortical hierarchy of structures that mediate scene recognition is established based on these data, and an attempt is made to determine the function of the individual components of the system.     

The prefrontal cortico-oculomotor trajectories in the monkey: A possible explanation for the effects of stimulation/lesion experiments on eye movement

Prefrontal corticofugal systems, as studied with anterograde HRP histochemistry, revealed projections to preoculomotor and oculomotor centers in the diencephalon and brainstem which may underlie direct cortical influence on eye movement. Because of the location of these preoculomotor trajectories, stimulation and lesion experiments affecting ocular motility may be explained by having involved prefrontal projections which have their origin in sulcus principalis or prearcuate area 8 (frontal eye field) cortex.     

Nucleus incertus--an emerging modulatory role in arousal, stress and memory

A major challenge in systems neuroscience is to determine the underlying neural circuitry and associated neurotransmitters and receptors involved in psychiatric disorders, such as anxiety and depression. A focus of many of these studies has been specific brainstem nuclei that modulate levels of arousal via their ascending monoaminergic projections (e.g. the serotonergic dorsal raphé, noradrenergic locus ceruleus and cholinergic laterodorsal tegmental nucleus). After years of relative neglect, the subject of recent studies in this context has been the GABAergic nucleus incertus,¹ which is located in the midline periventricular central gray in the ‘prepontine’ hindbrain, with broad projections throughout the forebrain. Nucleus incertus neurons express receptors for the stress hormone, corticotropin-releasing factor (CRF), are activated by psychological stressors, and project to key nuclei involved in stress responses and behavioral activation. The nucleus incertus is also a node in neural circuits capable of modulating hippocampal theta rhythm, which is related to control of spatial navigation and memory. A significant population of nucleus incertus neurons express the recently discovered, highly conserved neuropeptide, relaxin-3; and the recent availability of structurally-related, chimeric peptides that selectively activate or inhibit the relaxin-3 receptor, RXFP3, is facilitating studies of relaxin-3/RXFP3 networks and associated GABA and CRF systems. It is predicted that such targeted research will help elucidate the functions of ascending nucleus incertus pathways, including their possible involvement in arousal (sleep/wakefulness), stress reponses, and learning and memory; and in the pathology of related psychiatric diseases such as insomnia, anxiety and depression, and cognitive deficits.     

Short- and long-latency afferent inhibition; uses,mechanisms and influencing factors

Transcranial magnetic stimulation (TMS) is an ideal technique for non-invasively stimulating the brain and assessing intracortical processes. By delivering electrical stimuli to a peripheral nerve prior to a TMS pulse directed to the motor cortex, the excitability and integrity of the sensorimotor system can be probed at short and long time intervals (short latency afferent inhibition, long latency afferent inhibition). The goal of this review is to detail the experimental factors that influence the magnitude and timing of afferent inhibition in the upper limb and these include the intensity of nerve and TMS delivery, and the nerve composition. Second, the neural mechanisms of SAI are discussed highlighting the lack of existing knowledge pertaining to LAI. Third, the usage of SAI and LAI as a tool to probe cognition and sensorimotor function is explored with suggestions for future avenues of research.