Functional developmental similarities and differences in the neural correlates of verbal and nonverbal working memory tasks

Relatively little is known about the functional development of verbal and nonverbal working memory during adolescence. Behavioral studies have demonstrated that WM capacity increases with age, yet relatively few studies have assessed the relationship between brain-activity and age-related changes in WM capacity, especially as it differs across multiple domains. The present study used an n-back task and functional magnetic resonance imaging to assess age-related differences in the neural correlates of word and face working memory tasks. Seventy-eight individuals between the ages of 14 and 27 underwent scans while performing word and face "n-back" working memory tasks. We found very little evidence for age-related differences in accuracy and reaction time. We did find similarities and differences between adolescents and adults in the neural correlates of word and face working memory tasks, even in the absence of performance differences. More specifically, we found similar age-related differences in left superior parietal cortex for both word and face stimuli. We also found that age-related differences in a number of other regions (including left inferior frontal lobe, left supramarginal gyrus, left rolandic sulcus, right cerebellum and left fusiform gyrus) differed according to stimulus type. Our results provide further evidence for continued functional development through adolescence and into adulthood.     

Neural correlates of verbal and nonverbal working memory deficits in individuals with schizophrenia and their high-risk siblings

Impaired working memory and functional brain activation deficits within prefrontal cortex (PFC) may be associated with vulnerability to schizophrenia. This study compared working memory and PFC activation in individuals with schizophrenia, their unaffected siblings and healthy comparison participants. We administered a "2back" version of the "nback" task. Functional MRI (fMRI) was used to measure brain activity. Nineteen individuals with DSM-IV schizophrenia, 18 of their siblings, and 72 healthy comparison participants underwent fMRI scans while performing word and face "nback" working memory tasks. Repeated trials (items whose prior presentation was not in the correct nback position) allowed us to assess group differences in the ability to code the temporal order of items. Individuals with schizophrenia and their siblings performed worse than controls on repeated lure trials, suggesting an association between schizophrenia and impairments in the coding of temporal order within working memory. Both individuals with schizophrenia and their siblings also demonstrated abnormal brain activation in PFC, such that both groups had hyperactivation in response to word stimuli and hypoactivation in response to face stimuli. These results provide further evidence that individuals with schizophrenia and their siblings are impaired in their ability to encode the temporal order of items within working memory and that disturbances in working memory and PFC activation may be genetic markers of the vulnerability to schizophrenia.     

Electrophysiological correlates of verbal and tonal working memory

The present study's basic research question concerns differences in the processing of verbal and tonal stimuli in working memory. Participants had to rehearse sequences containing tonal and verbal information and to decide whether a subsequently presented probe stimulus belonged to the previously presented sequence. Electrophysiological measures were taken and analysed with regard to local (event-related potentials, ERP) and global (microstates) aspects. A larger N400 amplitude occurred for new compared to old items in the verbal, but not the tonal condition. The microstate analysis revealed differences in the specificity of several microstates for old compared to new items in the tonal and the verbal working memory condition. Corroborating previous results, the present study reveals differences in the efficiency of working memory processes for tonal compared to verbal stimuli with processes being more capable for the verbal compared to the tonal condition.     

Dissociation of neural correlates of verbal and non-verbal visual working memory with different delays

Background  

Dorsolateral prefrontal cortex (DLPFC), posterior parietal cortex, and regions in the occipital cortex have been identified as neural sites for visual working memory (WM). The exact involvement of the DLPFC in verbal and non-verbal working memory processes, and how these processes depend on the time-span for retention, remains disputed.     

Auditory working memory and verbal recall memory in schizotypy

Deficits on verbal memory tasks, as well as on spatial and auditory working memory tasks, have been observed in schizophrenia patients. A useful strategy in the determination of the premorbid indicator status of specific cognitive and memory deficits observed in patients is to examine those persons at increased biological risk for schizophrenia (e.g. first-degree relatives), schizotypal personality disorder patients, and/or psychometrically identified schizotypes for comparable deficits, though perhaps less profound than those seen in actual patients. We examined verbal memory and auditory working memory functioning in 31 schizotypic and 26 normal control subjects from a large randomly ascertained non-clinical university population. Schizotypy status was determined psychometrically using the well-known Perceptual Aberration Scale. Contrary to our theory-guided expectations, noteworthy deficits in verbal memory and auditory working memory were not observed in the schizotypic subjects and the two experimental groups did not differ significantly on any of the memory measures. These results were discussed in light of prior results obtained using the spatial delayed response task (i.e. spatial working memory) and Wisconsin Card Sorting Test performance on these same subjects. The theoretical implications of these findings are discussed in relation to the putative processes involved in the working memory system, as well as in relation to the schizotypy construct.     

Load matters: neural correlates of verbal working memory in children with autism spectrum disorder

Background

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterised by diminished social reciprocity and communication skills and the presence of stereotyped and restricted behaviours. Executive functioning deficits, such as working memory, are associated with core ASD symptoms. Working memory allows for temporary storage and manipulation of information and relies heavily on frontal-parietal networks of the brain. There are few reports on the neural correlates of working memory in youth with ASD. The current study identified the neural systems underlying verbal working memory capacity in youth with and without ASD using functional magnetic resonance imaging (fMRI).

Methods

Fifty-seven youth, 27 with ASD and 30 sex- and age-matched typically developing (TD) controls (9–16 years), completed a one-back letter matching task (LMT) with four levels of difficulty (i.e. cognitive load) while fMRI data were recorded. Linear trend analyses were conducted to examine brain regions that were recruited as a function of increasing cognitive load.

Results

We found similar behavioural performance on the LMT in terms of reaction times, but in the two higher load conditions, the ASD youth had lower accuracy than the TD group. Neural patterns of activations differed significantly between TD and ASD groups. In TD youth, areas classically used for working memory, including the lateral and medial frontal, as well as superior parietal brain regions, increased in activation with increasing task difficulty, while areas related to the default mode network (DMN) showed decreasing activation (i.e., deactivation). The youth with ASD did not appear to use this opposing cognitive processing system; they showed little recruitment of frontal and parietal regions across the load but did show similar modulation of the DMN.

Conclusions

In a working memory task, where the load was manipulated without changing executive demands, TD youth showed increasing recruitment with increasing load of the classic fronto-parietal brain areas and decreasing involvement in default mode regions. In contrast, although they modulated the default mode network, youth with ASD did not show the modulation of increasing brain activation with increasing load, suggesting that they may be unable to manage increasing verbal information. Impaired verbal working memory in ASD would interfere with the youths’ success academically and socially. Thus, determining the nature of atypical neural processing could help establish or monitor working memory interventions for ASD.

     

Event-related potential evidence of sex differences in verbal and nonverbal memory tasks

ERPs were recorded from 19 scalp electrodes while 48 subjects (24 females) performed visual recognition tasks for recurring verbal items and recurring abstract figures. Reaction times were longer in the figures than verbal task; the latencies of the ERP components (P2, N4, P3, P4) were also longer for the figures. A nonreversing asymmetry (R greater than L) was seen in both tasks. Significant task by electrode interactions (for P3, P4) were found, due to larger amplitudes anteriorly for the figures, but larger amplitudes posteriorly for the verbal task. All ERP latencies were longer for males than females. There were sex by task by electrode interactions in the amplitudes, due to larger ERPs (P2, N4) for females anteriorly for the figures, but slightly larger posteriorly for the verbal task. These results suggest that sex differences in cognitive abilities may be based on differences in biological mechanisms.     

Electrophysiological correlates of proactive interference in the ‘Recent Probes’ verbal working memory task

Using event-related potentials (ERPs), the present study examined the temporal dynamics of proactive interference in working memory using a recent probes task. Participants memorized and retained a target set of four letters over a short retention interval. They then responded to a recognition probe by judging whether it was from the memory set. ERP waveforms elicited by positive probes compared to those from negative probes showed positive shifts in a fronto-central early N2 component and a parietal late positive component (LPC). The LPC was identified as the electrophysiological signature of proactive interference, as it differentiated between two types of negative probes defined based on whether they were recently encountered. These results indicate that the proactive interference we observed arises from a mismatch between familiarity and contextual information during recognition memory. When considered together with related studies in the literature, the results also suggest that there are different forms of proactive interference associated with different neural correlates.     

Metabolic connectivity as index of verbal working memory

Positron emission tomography (PET) data are commonly analyzed in terms of regional intensity, while covariant information is not taken into account. Here, we searched for network correlates of healthy cognitive function in resting state PET data. PET with [¹⁸F]-fluorodeoxyglucose and a test of verbal working memory (WM) were administered to 35 young healthy adults. Metabolic connectivity was modeled at a group level using sparse inverse covariance estimation. Among 13 WM-relevant Brodmann areas (BAs), 6 appeared to be robustly connected. Connectivity within this network was significantly stronger in subjects with above-median WM performance. In respect to regional intensity, i.e., metabolism, no difference between groups was found. The results encourage examination of covariant patterns in FDG-PET data from non-neurodegenerative populations.     

Imaging phonological similarity effects on verbal working memory

Studies of verbal working memory (VWM) report that performance declines as the phonemic similarity of stimuli increases. To determine how phonological similarity affects brain function during VWM, "standard" and "similarity" versions of the 2-Back task were presented to 34 healthy participants during functional magnetic resonance imaging (FMRI). Letter consonants presented during similarity blocks rhymed, while consonants did not rhyme during standard blocks. Empirical ROIs were identified from significant 2-Back-related activity observed during either condition. A priori ROIs were selected from functional neuroimaging literature on phonological processing. Although VWM-related activity was not modulated by similarity in any of four regions recruited (dorsolateral prefrontal, posterior parietal, anterior insular, and supplementary motor cortices), four of five regions of deactivation exhibited significantly greater deactivation during the similarity compared to the standard condition (posterior cingulate, paracentral lobule, posterior insula, and parahippocampal gyrus). In a priori phonological processing-related ROIs, similarity did not affect observed increases in activity (supplementary motor area, Broca's area, and cerebellum), while two of the three regions exhibiting decreased activity (near Wernicke's area and Heschel's Gyrus) also exhibited more deactivation during similarity. Accuracy was lower during the similarity 2-Back, positively related to activity within recruited VWM-related ROIs, and inversely related to activity in regions of VWM-related deactivation. Based on known functions of these ROIs, we conclude that language, audition, and self-reflection processes may disengage during phonological interference, while activity levels are maintained in regions recruited during VWM processing. Similarity effects likely include suspension of attention to unrelated and distracting processes to improve concentration.     

Cerebellar transcranial magnetic stimulation impairs verbal working memory

Previous functional magnetic resonance imaging and patient studies indicate cerebellar participation in verbal working memory. In particular, event-related functional magnetic resonance imaging showed superior cerebellar activation during the initial encoding phase of the Sternberg task. This study used functional magnetic resonance imaging-guided transcranial magnetic stimulation (TMS) to test whether disruption of the right superior cerebellum (hemispheric lobule VI/Crus I) impairs verbal working memory performance. Single-pulse TMS was administered immediately after letter presentation during the encoding phase on half the trials. Sham TMS and a Motor Control task were included to test for general distraction and nonmemory-related motor effects. Results showed no effects of TMS on accuracy, but reaction times (RTs) on correct trials were significantly increased on TMS relative to non-TMS trials for the Verbal Working Memory and Motor Control tasks. Additional analyses showed that the increased RT was significantly greater for Verbal Working Memory than for the motor task, suggesting that the effect on working memory was not caused by interference with finger responses. Sham TMS did not affect RTs, indicating that the potentially distracting effects of the postencoding click did not contribute to the increase in RT. The observed effects from cerebellar disruption are consistent with proposed cerebrocerebellar involvement in verbal working memory.     

Intact verbal and nonverbal short-term memory following damage to the human hippocampus.

Short-term memory was assessed in two groups of amnesic patients. Six patients had confirmed or suspected damage to the hippocampal formation, and six patients had diencephalic damage as a result of alcoholic Korsakoff's syndrome. Verbal short-term memory was evaluated with seven separate administrations of the standard digit span test in order to obtain a precise measure of short-term memory. Nonverbal short-term memory was evaluated with four tests that assessed apprehension, retention, and the ability to manipulate nonverbal material--all within the span of immediate memory. One of these four tests assessed short-term memory for spatial location. Patients with damage to the hippocampal formation had a digit span equivalent to that of control subjects and also performed normally on the four tests of nonverbal short-term memory. The patients with Korsakoff's syndrome had a marginally low digit span and performed poorly on three of the four nonverbal tasks, a finding consistent with the deficits in attention and visuospatial processing previously described for this patient group. These deficits are likely due to the frontal lobe atrophy typically associated with Korsakoff's syndrome, rather than to diencephalic damage. The results support the view that short-term (immediate) memory, including short-term spatial memory, is independent of the hippocampus.     

Neural correlates of consolidation in working memory

Many of our daily activities rely on a brain system called working memory, which implements our ability to encode information for short-term maintenance, possible manipulation, and retrieval. A recent intracranial study of patients performing a paradigmatic working memory task revealed that the maintenance of information involves a distributed network of oscillations in the gamma band (>40 Hz). Using a similar task, we focused on the encoding stage and targeted a process referred to as short-term consolidation, which corresponds to the encoding of novel items in working memory. The paradigm was designed to manipulate the subjects' intention to encode: series of 10 letters were presented, among which only five had to be remembered, as indicated by visual cues preceding or following each letter. During this task we recorded the intracerebral EEG of nine epileptic patients implanted in mesiotemporal structures, perisylvian regions, and prefrontal areas and used time-frequency analysis to search for neural activities simultaneous with the encoding of the letters into working memory. We found such activities in the form of increases of gamma band activity in a set of regions associated with the phonological loop, including the Broca area and the auditory cortex, and in the prefrontal cortex, the pre- and postcentral gyri, the hippocampus, and the fusiform gyrus.     

A cross-language study of verbal and visuospatial working memory span

This cross-language study of working memory compared 30 English speakers and 30 Mandarin Chinese speakers on backward and forward digit and spatial span. Mandarin speakers had greater spans on forward digit and spatial span than did English speakers. Effects were most significant for digit span where the mean score of the English speakers was equivalent to the lowest individual score from Mandarin speakers. Shorter articulation time for digits in spoken Mandarin may account for higher digit spans than those observed in English. The current study indicates that clinical applications of working memory tests should consider cross-language effects, particularly in the evaluation of verbal working memory deficits.     

Brain connectivity during verbal working memory in children and adolescents

Working memory (WkM) is a fundamental cognitive process that serves as a building block for higher order cognitive functions. While studies have shown that children and adolescents utilize similar brain regions during verbal WkM, there have been few studies that evaluate the developmental differences in brain connectivity. Our goal was to study the development of brain connectivity related to verbal WkM in typically developing children and adolescents. Thirty‐five healthy children and adolescents, divided into three groups: 9–12 (children), 13–16 (young adolescents), and 17–19 (older adolescents) years, were included in this functional magnetic resonance imaging (fMRI) study. The verbal WkM task involved a modified Sternberg item recognition paradigm using three different loads. Brain connectivity analysis was performed using independent component analyses and regressing the components with the design matrix to determine task‐related networks. Connectivity analyses resulted in four components associated solely with encoding, four solely with recognition and two with both. Two networks demonstrated age‐related differences with respect to load, (1) the left motor area and right cerebellum, and 2) the left prefrontal cortex, left parietal lobe, and right cerebellum. Post hoc analyses revealed that the first network showed significant effects of age between children and the two older groups. There was increasing connectivity with increasing load for adolescents. The second network demonstrated age‐related differences between children and older adolescents. Children have higher task‐related connectivity at lower loads, but they tend to equalize with the adolescents with higher loads. Finally, a non‐load related network involving the orbital frontal and anterior cingulate cortices showed less connectivity in children. Hum Brain Mapp 35:698–711, 2014. © 2012 Wiley Periodicals, Inc.     

Neuroarchitecture of verbal and tonal working memory in nonmusicians and musicians

Working memory (WM) for auditory information has been thought of as a unitary system, but whether WM for verbal and tonal information relies on the same or different functional neuroarchitectures has remained unknown. This fMRI study examines verbal and tonal WM in both nonmusicians (who are trained in speech, but not in music) and highly trained musicians (who are trained in both domains). The data show that core structures of WM are involved in both tonal and verbal WM (Broca's area, premotor cortex, pre‐SMA/SMA, left insular cortex, inferior parietal lobe), although with significantly different structural weightings, in both nonmusicians and musicians. Additionally, musicians activated specific subcomponents only during verbal (right insular cortex) or only during tonal WM (right globus pallidus, right caudate nucleus, and left cerebellum). These results reveal the existence of two WM systems in musicians: A phonological loop supporting rehearsal of phonological information, and a tonal loop supporting rehearsal of tonal information. Differences between groups for tonal WM, and between verbal and tonal WM within musicians, were mainly related to structures involved in controlling, programming and planning of actions, thus presumably reflecting differences in action‐related sensorimotor coding of verbal and tonal information. Hum Brain Mapp 32:771–783, 2011. © 2010 Wiley‐Liss, Inc.     

Human verbal working memory impairments associated with thalamic damage

Although animal studies, human neuroimaging studies, and numerous theoretical models suggest possible contributions of the thalamus to working memory, there are very few reported deficits in human working memory following thalamic lesions. The present study examined working memory performance in six individuals with isolated thalamic stroke and found evidence of impairment on a number of working memory span tasks, but not on a forward digit-span measure. Examination of additional aspects of working memory performance (e.g., spatial and object working memory), analysis of subjects with other sites of thalamic stroke, and functional neuroimaging suggest a role of the thalamus in working memory.     

Spatio-temporal dynamics of working memory maintenance and scanning of verbal information

ObjectiveDuring verbal communication, humans briefly maintain mental representations of speech sounds conveying verbal information, and constantly scan these representations for comparison to incoming information. We determined the spatio-temporal dynamics of such short-term maintenance and subsequent scanning of verbal information, by intracranially measuring high-gamma activity at 70–110 Hz during a working memory task.MethodsPatients listened to a stimulus set of two or four spoken letters and were instructed to remember those letters over a two-second interval, following which they were asked to determine if a subsequent target letter had been presented earlier in that trial’s stimulus set.ResultsAuditory presentation of letter stimuli sequentially elicited high-gamma augmentation bilaterally in the superior-temporal and pre-central gyri. During the two-second maintenance period, high-gamma activity was augmented in the left pre-central gyrus, and this effect was larger during the maintenance of stimulus sets consisting of four compared to two letters. During the scanning period following target presentation, high-gamma augmentation involved the left inferior-frontal and supra-marginal gyri.ConclusionsShort-term maintenance of verbal information is, at least in part, supported by the left pre-central gyrus, whereas scanning by the left inferior-frontal and supra-marginal gyri.SignificanceThe cortical structures involved in short-term maintenance and scanning of speech stimuli were segregated with an excellent temporal resolution.