Limits to the capacity of visual short-term memory (VSTM) indicate a maximum storage of only 3 or 4 items. Recently, it has been suggested that activity in a specific part of the brain, the posterior parietal cortex (PPC), is correlated with behavioral estimates of VSTM capacity and might reflect a capacity-limited store. In three experiments that varied the delay period and the stimuli to be stored, we found dissociations between functional magnetic resonance imaging (fMRI) activity in PPC and behavioral measures of capacity. When the delay length increased, fMRI activity in this area increased with memory load beyond the behaviorally determined limits of capacity. The results suggest that activity in PPC may reflect the attentional demands of short-term memory rehearsal processes rather than capacity limitations, and imply that a larger number of items than that determined by behavioral measures of capacity may be rehearsed during STM tasks. This account is consistent with the role of PPC in attentional processes and with the close correlation between brain areas that are involved in attention and those that mediate STM.

Attention deficit hyperactivity disorder (ADHD) frequently persists into adulthood. A reduction in visual short-term memory (vSTM) storage capacity was recently suggested as a potential neuro-cognitive endophenotype, i.e., a testable marker of an individual's liability for developing ADHD. This study aimed at identifying markers of the brain abnormalities underlying vSTM reductions in adult ADHD. We combined behavioral parameter-based assessment with electrophysiology in groups of adult ADHD patients and healthy age-matched controls. Amplitudes of ERP markers of vSTM storage capacity, the contralateral delay activity (CDA) and the P3b, were analyzed according to (i) differences between individuals with higher vs. lower storage capacity K and (ii) differences between ADHD patients and control participants. We replicated the finding of reduced storage capacity in adult ADHD. Across groups, individuals with higher relative to lower storage capacity showed a larger CDA and P3b. We further found differences between the patient and control groups in the ERPs: The CDA amplitude was attenuated in an early time window for ADHD patients compared to control participants, and was negatively correlated with ADHD patients' symptom severity ratings. Furthermore, the P3b was larger in ADHD patients relative to control participants. These electrophysiological findings indicate altered brain mechanisms underlying visual storage capacity in ADHD, which are characterized by deficient encoding and maintenance, and increased recruitment of control processes. Accordingly, (quantifiable) ERP markers of vSTM in adult ADHD bear candidacy as neuro-cognitive endophenotypes of the disease.

Recent studies have shown that top-down attention biases task-relevant representations in visual short-term memory (VSTM). Accumulating evidence has also revealed the modulatory effects of emotional arousal on attentional processing. However, it remains unclear how top-down attention interacts with emotional memoranda in VSTM. In this study, we investigated the mechanisms of alpha oscillations and their spatiotemporal characteristics that underlie top-down attention to threatening representations during VSTM maintenance with electroencephalography. Participants were instructed to remember a threatening object and a neutral object in a cued variant delayed response task. Retrospective cues (retro-cues) were presented to direct attention to the hemifield of a threatening object (i.e., cue-to-threat trials) or a neutral object (i.e., cue-to-neutral trials) during a retention interval prior to the probe test. We found a significant retro-cue-related alpha lateralisation over posterior regions during VSTM maintenance. The novel finding was that the magnitude of alpha lateralisation was greater for cue-to-threat objects compared to cue-to-neutral ones. These results indicated that directing attention towards threatening representations compared to neutral representations could result in greater regulation of alpha activity contralateral to the cued hemifield. Importantly, we estimated the spatiotemporal pattern similarity in alpha activity and found significantly higher similarity indexes for the posterior regions relative to the anterior regions and for the cue-to-threat objects relative to cue-to-neutral objects over the posterior regions. Together, our findings provided the oscillatory evidence of greater top-down modulations of alpha lateralisation and spatiotemporal pattern similarity for attending to threatening representations in VSTM.

Studies on verbal learning in patients with impaired verbal short-term memory (vSTM) have revealed dissociations among types of verbal information. Patients with impaired vSTM are able to learn lists of known words but fail to acquire new word forms. This suggests that vSTM is involved in new word learning. The present study assessed both new word learning and the learning of digit sequences in two patients with impaired vSTM. In two experiments, participants were required to learn people's names, ages and professions, or their four digit 'phone numbers'. The STM patients were impaired on learning unknown family names and phone numbers, but managed to acquire other verbal information. In contrast, a patient with a severe verbal episodic memory impairment was impaired across information types. These results indicate verbal STM involvement in the learning of digit sequences.

Neuroimaging studies attempting to isolate the neural substrate of visual short-term memory in humans have concentrated on the behavior of neurons populating the posterior part of the parietal cortex as a possible source of visual short-term memory capacity limits. Using a standard change-detection task, fMRI studies have shown that maintenance of bilaterally encoded objects elicited bilateral increases of hemodynamic activation in the intra-parietal and intra-occipital sulci (IPS-IOS) proportional to the number of objects retained in visual short-term memory. We used a spatially cued variant of the change-detection task to record hemodynamic responses to unilaterally encoded objects using functional near-infrared spectroscopy (fNIRS). Electrophysiological studies that employed this task have shown that maintenance of unilaterally encoded objects elicited posterior unilateral (contralateral) increase in event-related negativity proportional to the number of objects retained in visual short-term memory. We therefore examined whether contralateral increases in oxy-hemoglobin concentration correlated with the number of retained objects. Contrary to the idea that bilateral increases in BOLD responses and unilateral increases in event-related negativity may be different reflections of the same underlying neural/functional processing, memory-related increases in oxy-hemoglobin concentration were found bilaterally even when objects had to be encoded unilaterally. The present findings suggest that EEG and fMRI/fNIRS techniques reveal distinct neural signatures of the mechanisms supporting visual short-term memory.

The anatomical segregation of executive control processes within the prefrontal cortex remains poorly defined. The present study focused on strategy implementation on two working memory tasks: the CANTAB spatial working memory task and a visuospatial sequence generation task. These measures were administered to a group of frontal lesion patients and a comparison group of healthy subjects. Frontal patients with damage to the right inferior frontal gyrus were impaired on the CANTAB spatial working memory task, compared with healthy controls and patients without damage to this region. This deficit was most strongly related to the pars opercularis subregion (BA44) and was accompanied by poor strategy usage. On the sequence generation task, frontal lesion patients were impaired on a strategy-training phase when the working memory demands of the task were reduced, but had relatively intact performance on other phases of the task. Performance on the training phase was correlated with the amount of damage to the dorsolateral prefrontal cortex (DLPFC: BA46/9). These results support theoretical notions of prefrontal cortical function that emphasise its contribution to executive processes such as mnemonic strategies and monitoring over its role as a short-term memory store. Moreover, we provide evidence for the first time that such functions are dependent on dissociable brain regions within the prefrontal cortex.

The contributions of the hippocampal formation and adjacent regions of the medial temporal lobe (MTL) to memory are still a matter of debate. It is currently unclear, to what extent discrepancies between previous human lesion studies may have been caused by the choice of distinct patient models of MTL dysfunction, as disorders affecting this region differ in selectivity, laterality and mechanisms of post-lesional compensation. Here, we investigated the performance of three distinct patient groups with lesions to the MTL with a battery of visuo-spatial short-term memory tasks. Thirty-one subjects with either unilateral damage to the MTL (postsurgical lesions following resection of a benign brain tumor, 6 right-sided lesions, 5 left) or bilateral damage (10 post-encephalitic lesions, 10 post-anoxic lesions) performed a series of tasks requiring short-term memory of colors, locations or color-location associations. We have shown previously that performance in the association task critically depends on hippocampal integrity. Patients with postsurgical damage of the MTL showed deficient performance in the association task, but performed normally in color and location tasks. Patients with left-sided lesions were almost as impaired as patients with right-sided lesions. Patients with bilateral post-encephalitic lesions showed comparable damage to MTL sub-regions and performed similarly to patients with postsurgical lesions in the association task. However, post-encephalitic patients showed additional impairments in the non-associative color and location tasks. A strikingly similar pattern of deficits was observed in post-anoxic patients. These results suggest a distinct cerebral organization of associative and non-associative short-term memory that was differentially affected in the three patient groups. Thus, while all patient groups may provide appropriate models of medial temporal lobe dysfunction in associative visuo-spatial short-term memory, additional deficits in non-associative memory tasks likely reflect damage of regions outside the MTL. Importantly, the choice of a patient model in human lesion studies of the MTL significantly influences overall performance patterns in visuo-spatial memory tasks.

Several theories of brain function emphasize distinctions between sensory and cognitive systems. We hypothesized, instead, that sensory and cognitive systems interact to instantiate the task at the neural level. We tested whether input modality interacts with working memory operations in that, despite similar cognitive demands, differences in the anatomical locations or temporal dynamics of activations following auditory or visual input would not be limited to the sensory cortices. We recorded event-related brain potentials (ERPs) while participants performed simple short-term memory tasks involving visually or auditorily presented bandpass-filtered noise stimuli. Our analyses suggested that working memory operations in each modality had a very similar spatial distribution of current sources outside the sensory cortices, but differed in terms of time course. Specifically, information for visual processing was updated and held online in a manner that was different from auditory processing, which was done mostly after the offset of the final stimulus. Our results suggest that the neural networks that support working memory operations have different temporal dynamics for auditory and visual material, even when the stimuli are matched in term of discriminability, and are designed to undergo very similar transformations when they are encoded and retrieved from memory.

We ask the question whether the coding of categorical versus coordinate spatial relations depends on different neural networks showing hemispheric specialization or whether there is continuity between these two coding types. The 'continuous spatial coding' hypothesis would mean that the two coding types rely essentially on the same neural network consisting of more general-purpose processes, such as visuo-spatial attention, but with a different weighting of these general processes depending on exact task requirements. With event-related fMRI, we have studied right-handed male subjects performing a grid/no-grid visuo-spatial working memory task inducing categorical and coordinate spatial relations coding. Our data support the 'continuous spatial coding' hypothesis, indicating that, while based on the same fronto-parieto-occipital neural network than categorical spatial relations coding, the coding of coordinate spatial relations relies more heavily on attentional and executive processes, which could induce hemispheric differences similar to those described in the literature. The results also show that visuo-spatial working memory consists of a short-term posterior store with a capacity of up to three elements in the parietal and extrastriate cortices. This store depends on the presence of a visible space categorization and thus can be used for the coding of categorical spatial relations. When no visible space categorization is given or when more than three elements have to be coded, additional attentional and executive processes are recruited, mainly located in the dorso-lateral prefrontal cortex.

Paired associates learning is impaired in both schizophrenia and amnestic mild cognitive impairment (aMCI), which may reflect hippocampal pathology. In addition, schizophrenia is characterized by the dysfunction of the retino-geniculo-striatal magnocellular (M) visual pathway. The purpose of this study was to investigate the interaction between visual perceptual and memory dysfunctions. We administered a modified version of the CANTAB paired associates learning task to patients with schizophrenia (n=20), aMCI (n=20), and two groups of matched healthy controls (n=20 for each patient group). The stimuli in the paired associates learning task biased information processing toward the M pathways (low contrast, low spatial frequency) and parvocellular (P) pathways (high contrast, high spatial frequency). Results revealed that patients with schizophrenia exhibited a more pronounced learning deficit for M-biased relative to P-biased stimuli. In aMCI, there were similar memory deficits for both types of stimuli. Orientation discrimination for M- and P-biased stimuli was intact in both groups of patients. The number of errors in the M-biased memory condition significantly and inversely correlated with the volume of the right hippocampus in schizophrenia. These results suggest an interaction between M-biased perceptual processing and short-term relational memory in schizophrenia, which may be associated with the structural alteration of the right hippocampus.

The basal ganglia are critically involved in language control (LC) processes, allowing a bilingual to utter correctly in one language without interference from the non-requested language. It has been hypothesized that the neural mechanism of LC closely resembles domain-general executive control (EC). The purpose of the present study is to investigate the integrity of bilingual LC and its overlap with domain-general EC in a clinical population such as individuals with Parkinson's disease (PD), notoriously associated with structural damage in the basal ganglia. We approach these issues in two ways. First, we employed a language switching task to investigate the integrity of LC in a group of Catalan-Spanish bilingual individuals with PD, as compared to a group of matched healthy controls. Second, to test the relationship between domain-general EC and LC we compared the performances of individuals with PD and healthy controls also in a non-linguistic switching task. We highlight that, compared to controls, individuals with PD report decreased processing speed, less accuracy and larger switching costs in terms of RT and errors in the language switching task, whereas in the non-linguistic switching task PD patients showed only increased switching cost in terms of errors. However, we report a positive correlation between the magnitudes of linguistic and non-linguistic mixing costs in individuals with PD. Taken together, these results support the notion of a critical role of the basal ganglia and connected structures in LC, and suggest a possible link between LC and domain-general EC.

Visual short-term memory (VSTM) capacity is often assessed using change detection tasks, and individual differences in performance have been shown to predict cognitive aptitudes across a range of domains in children and adults. We recently showed that intelligence correlates with an attentional component necessary for change detection rather than with memory capacity per se (Cusack, Lehmann, Veldsman, & Mitchell, 2009). It remained unclear, however, whether different attentional strategies during change detection have most impact during the encoding or maintenance of information. Here we present recent findings from our laboratory supporting the hypothesis that attentional selection during encoding dominates individual differences in change detection measures of visual short-term memory. In a first study, we unpredictably varied whether short-term memory was probed using change detection or whole report, encouraging participants to adopt the same encoding strategy throughout the tasks. Change detection performance of lower-IQ individuals improved. In a second study, we found that deficits in top-down attentional selectivity can be alleviated in participants with low change detection performance by providing helpful grouping information during encoding. Finally, a meta-analysis of neuroimaging data from 112 participants performing a variety of VSTM tasks showed that performance correlates with activity in several parietal and frontal regions during the encoding but not the maintenance phase. Taken together, these results support the notion that encoding strategy and not short-term memory capacity itself largely determines individual differences in visual change detection performance.

Visual short-term memory (VSTM) and visual imagery are believed to involve overlapping neuronal representations in the early visual cortex. While a number of studies have provided evidence for this overlap, at the behavioral level VSTM and imagery are dissociable processes; this begs the question of how their neuronal mechanisms differ. Here we used transcranial magnetic stimulation (TMS) to examine whether the neural bases of imagery and VSTM maintenance are dissociable in the early visual cortex (EVC). We intentionally used a similar task for VSTM and imagery in order to equate their assessment. We hypothesized that any differential effect of TMS on VSTM and imagery would indicate that their neuronal bases differ at the level of EVC. In the "alone" condition, participants were asked to engage either in VSTM or imagery, whereas in the "concurrent" condition, each trial required both VSTM maintenance and imagery simultaneously. A dissociation between VSTM and imagery was observed for reaction times: TMS slowed down responses for VSTM but not for imagery. The impact of TMS on sensitivity did not differ between VSTM and imagery, but did depend on whether the tasks were carried concurrently or alone. This study shows that neural processes associated with VSTM and imagery in the early visual cortex can be partially dissociated.

Normal aging is usually accompanied by several structural and functional physiological changes of the brain, which are closely related to alterations of cognitive functions (e.g., visual short-term memory). As the average age of the population increases, it has become crucial to identify cognitive-behavioural interventions to maintain a healthy level of cognitive performance. Among a variety of approaches, the targeting of specific intrinsic alertness mechanisms has shown a solid rationale and beneficial effects in both healthy and pathological ageing. In a similar vein, the use of non-invasive transcranial electrical stimulation (tES) represents another promising approach to induce an alerting state that can produce advantages in the information processing in the brain and therefore behaviour. Here, we investigated whether time-locked bursts of tES (i.e., transcranial random noise stimulation) were effective in inducing behavioural and physiological changes, consistently with an alertness increase, in both young and older healthy adults. Namely, we expected to find a beneficial alerting effect on visual short-term memory performance as a function of stimulus perceptual salience and tES. The initial results showed that the performance of younger adults was not affected by tES, while older adults scored lower correct responses for high-salience stimuli during real tES with respect to sham stimulation. However, after including a baseline measure of subjective level of alertness in the analyses, a tES-induced memory improvement did emerge in the less alerted younger adults, while only the more alerted older adults were subject to the worsening effect by tES. We discuss these results in consideration of the evidence on critical age-related differences as well as the interaction between neurostimulation and baseline alerting mechanisms.

Although activity in premotor and motor cortices is commonly observed in neuroimaging studies of spoken language processing, the degree to which this activity is an obligatory part of everyday speech comprehension remains unclear. We hypothesised that rather than being a unitary phenomenon, the neural response to speech perception in motor regions would differ across listeners as a function of individual cognitive ability. To examine this possibility, we used functional magnetic resonance imaging (fMRI) to investigate the neural processes supporting speech perception by comparing active listening to pseudowords with matched tasks that involved reading aloud or repetition, all compared to acoustically matched control stimuli and matched baseline tasks. At a whole-brain level there was no evidence for recruitment of regions in premotor or motor cortex during speech perception. A focused region of interest analysis similarly failed to identify significant effects, although a subset of regions approached significance, with notable variability across participants. We then used performance on a battery of behavioural tests that assessed meta-phonological and verbal short-term memory abilities to investigate the reasons for this variability, and found that individual differences in particular in low phonotactic probability pseudoword repetition predicted participants' neural activation within regions in premotor and motor cortices during speech perception. We conclude that normal listeners vary in the degree to which they recruit premotor and motor cortex as a function of short-term memory ability. This is consistent with a resource-allocation approach in which recruitment of the dorsal speech processing pathway depends on both individual abilities and specific task demands.

Positron emission tomography (PET) was performed in normal volunteers during a serial recall task under the influence of irrelevant speech comprising both single item repetition and multi-item sequences. An interaction approach was used to identify brain areas specifically related to the irrelevant speech effect. We interpreted activations as compensatory recruitment of complementary working memory processing, and decreased activity in terms of suppression of task relevant areas invoked by the irrelevant speech. The interaction between the distractors and working memory revealed a significant effect in the left, and to a lesser extent in the right, superior temporal region, indicating that initial phonological processing was relatively suppressed. Additional areas of decreased activity were observed in an a priori defined cortical network related to verbal working memory, incorporating the bilateral superior temporal and inferior/middle frontal cortices extending into Broca's area on the left. We also observed a weak activation in the left inferior parietal cortex, a region suggested to reflect the phonological store, the subcomponent where the interference is assumed to take place. The results suggest that the irrelevant speech effect is correlated with and thus tentatively may be explained in terms of a suppression of components of the verbal working memory network as outlined. The results can be interpreted in terms of inhibitory top-down attentional mechanisms attenuating the influence of the irrelevant speech, although additional studies are clearly necessary to more fully characterize the nature of this phenomenon and its theoretical implications for existing short-term memory models.

This study explores the morphosyntactic processing deficit in developmental dyslexia, addressing the on-going debate on the linguistic nature of the disorder, and directly testing the hypothesis that the deficit is based on underlying processing difficulties, such as acoustic and/or phonological impairments. Short German sentences consisting of a pronoun and a verb, either correct or containing a morphosyntactic violation, were auditorily presented to 17 German-speaking adults with dyslexia, and 17 matched control participants, while an EEG was recorded. In order to investigate the interaction between low-level phonological processing and morphosyntactic processing, the verbal inflections were manipulated to consist of different levels of acoustic salience. The event-related potential (ERP) results confirm altered morphosyntactic processing in participants with dyslexia, especially when morphosyntactic violations are expressed by both lexical and inflectional changes. Moreover, ERP data on phoneme discrimination and behavioural data on phonemic awareness and verbal short-term memory reveal phonological deficits in dyslexic participants. However, a causal relationship between phonological and morphosyntactic processing was not conclusive, because anomalous morphosyntactic processing in dyslexia is not directly mediated by acoustic salience, rather it correlates with high-level phonological skills and is mediated by lexical cues.

Noise-vocoded speech is a spectrally highly degraded signal, but it preserves the temporal envelope of speech. Listeners vary considerably in their ability to adapt to this degraded speech signal. Here, we hypothesised that individual differences in adaptation to vocoded speech should be predictable by non-speech auditory, cognitive, and neuroanatomical factors. We tested 18 normal-hearing participants in a short-term vocoded speech-learning paradigm (listening to 100 4-band-vocoded sentences). Non-speech auditory skills were assessed using amplitude modulation (AM) rate discrimination, where modulation rates were centred on the speech-relevant rate of 4 Hz. Working memory capacities were evaluated (digit span and nonword repetition), and structural MRI scans were examined for anatomical predictors of vocoded speech learning using voxel-based morphometry. Listeners who learned faster to understand degraded speech also showed smaller thresholds in the AM discrimination task. This ability to adjust to degraded speech is furthermore reflected anatomically in increased grey matter volume in an area of the left thalamus (pulvinar) that is strongly connected to the auditory and prefrontal cortices. Thus, individual non-speech auditory skills and left thalamus grey matter volume can predict how quickly a listener adapts to degraded speech.

Since the 1960s, evidence from healthy participants and brain-damaged patients, neuroimaging and non-invasive brain stimulation studies has specified the neurofunctional architecture of the short-term memory (STM) system, supporting the temporary retention of a limited amount of verbal material. Auditory-verbal, later termed Phonological (Ph) STM or Phonological Loop, comprises two sub-components: i) the main storage system, the Phonological Short-Term Store (PhSTS), to which auditory verbal stimuli have direct access and where phonologically coded information is retained for a few seconds; ii) a Rehearsal Process (REH), which actively maintains the trace held in the PhSTS, preventing its decay and conveys visual verbal material to the PhSTS, after the process of Phonological Recoding (PhREC, or Grapheme-to-Phoneme Conversion) has taken place. PhREC converts visuo-verbal graphemic representations into phonological ones. The neural correlates of PhSTM include two discrete regions in the left hemisphere: the temporo-parietal junction (PhSTS) and the inferior frontal gyrus in the premotor cortex (REH). The neural basis of PhREC has been much less investigated. A few single case studies of patients made anarthric by focal or degenerative cortical damage, who show a pattern of impairment indicative of a deficit of PhREC, sparing the REH process, suggest that the primary motor cortex (M1) might be involved. To test this hypothesis in healthy participants with a neurophysiological approach, we measured the corticospinal excitability of M1, by means of Transcranial Magnetic Stimulation (TMS)-induced Motor Evoked Potentials (MEPs), during the execution of phonological judgements on auditorily vs. visually presented words (Experiment #1). Crucially, these phonological tasks involve REH, while PhREC is required only with visual presentation. Results show MEPs with larger amplitude when stimuli are presented visually. Task difficulty does not account for this difference and the result is specific for linguistic stimuli, indeed visual and auditory stimuli that cannot be verbalized lead to different behavioral and neurophysiological patterns (Experiment #2). The increase of corticospinal excitability when words are presented visually can be then interpreted as an indication of the involvement of M1 in PhREC. The present findings elucidate the neural correlates of PhREC, suggesting an involvement of the peripheral motor system in its activity.

Recently there has been a growing interest in visual short-term memory (VSTM) including the neural basis of the function. Processing speed, another main aspect of visual attention capacity, has received less investigation. For both cognitive functions human lesion studies are sparse. We used a whole report experiment for estimation of these two parameters in 22 patients with right side stroke. Psychophysical performance was analyzed using Bundesen's [Bundesen, C. (1990). A theory of visual attention. Psychological Review, 97, 523-547] Theory of Visual Attention (TVA) and compared statistically to lesion location and size measured by MRI. Visual processing speed was impaired in the contralesional hemifield for most patients, but typically preserved ipsilesionally, even after large cortico-subcortical lesions. When bilateral deficits in processing speed occurred, they were related to damage in the right middle frontal gyrus or leukoaraiosis. The storage capacity of VSTM was also normal for most patients, but deficits were found after severe leukoaraiosis or large strokes extending deep into white matter. Thus, the study demonstrated the importance of white-matter connectivity for both VSTM capacity and ipsilesional processing speed. The study also showed that lesions in a large region of the right hemisphere, including the putamen, insula, and inferior frontal cortex, do not lead to general deficits in the capacity of visual attention.