Automatic and intrinsic auditory "what" and "where" processing in humans revealed by electrical neuroimaging

The auditory system includes 2 parallel functional pathways-one for treating sounds' identities and another for their spatial attributes (so-called "what" and "where" pathways). We examined the spatiotemporal mechanisms along auditory "what" and "where" pathways and whether they are automatically engaged in differentially processing spatial and pitch information of identical stimuli. Electrical neuroimaging of auditory evoked potentials (i.e., statistical analyses of waveforms, field strength, topographies, and source estimations) was applied to a passive "oddball" paradigm comprising 2 varieties of blocks of trials. On "what" blocks, band-pass-filtered noises varied in pitch, independently of perceived location. On "where" blocks, the identical stimuli varied in perceived location independently of pitch. Beginning 100 ms poststimulus, the electric field topography significantly differed between conditions, indicative of the automatic recruitment of distinct intracranial generators. A distributed linear inverse solution and statistical analysis thereof revealed activations within superior temporal cortex and prefrontal cortex bilaterally that were common for both conditions, as well as regions within the right temporoparietal cortices that were selective for the "where" condition. These findings support models of automatic and intrinsic parallel processing of auditory information, such that segregated processing of spatial and pitch features may be an organizing principle of auditory function.     

Visual area V5/MT remembers "what" but not "where"

Priming for motion direction has been shown to depend upon the functional integrity of extrastriate area V5/MT. Its retinotopic organization and the interactions recently found between motion adaptation and misperceived localization may suggest, for this area, a role for priming of spatial position in addition to the established priming of motion direction. Disruption of V5/MT with repetitive transcranial magnetic stimulation during the intertrial interval had the effect of abolishing priming of motion direction but no effect in priming of spatial position. These effects cannot be explained in terms of perception or task demands but only in terms of the effects of information irrelevant to the correct performance of the task stored over the intertrial interval. We suggest that the attribute of spatial position might be stored in short-term memory either in earlier areas of the motion pathways such as V3 or in higher cortical areas traditionally associated with the analysis of spatial information, for example, posterior parietal cortex or the frontal eye fields.     

Age-related differences in brain activity underlying working memory for spatial and nonspatial auditory information

We used functional magnetic resonance imaging and a 1-back task to assess working memory (WM) for spatial (sound location) and nonspatial (sound category) auditory information in younger and older adults. A mixed block-event-related design was used to measure sustained activity during each task block and transient activity to targets (repetitions of location or category). In both groups, there was increased sustained activity for category WM in left anterior temporal cortex and inferior prefrontal cortex (PFC) and increased activity for location WM in right inferior parietal cortex and dorsal PFC. There were no reliable age differences in this pattern of activity. Older adults had more sustained activity than younger adults in left PFC during both tasks, suggesting that additional PFC recruitment in older adults reflects nonspecific engagement of frontally mediated task-monitoring processes. Both groups showed lower transient than sustained activity in auditory cortex bilaterally; however, older adults showed smaller target-related reductions of activity during the category task. A greater reduction of activity to category targets in left auditory cortex was associated with better performance on this task in older adults, suggesting that a failure to modulate activity appropriately when a stimulus is repeated, or when a particular feature of the stimulus is repeated, could lead to reduced ability to detect this repetition.     

Striatal dopamine and working memory

Recent studies have emphasized the importance of dopamine projections to the prefrontal cortex (PFC) for working memory (WM) function, although this system has rarely been studied in humans in vivo. However, dopamine and PFC activity can be directly measured with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), respectively. In this study, we examined WM capacity, dopamine, and PFC function in healthy older participants in order to test the hypothesis that there is a relationship between these 3 factors. We used the PET tracer 6-[18F]fluoro-L-m-tyrosine to measure dopamine synthesis capacity in the striatum (caudate, putamen), and event-related fMRI to measure brain activation during different epochs (cue, delay, probe) of a WM task. Caudate (but not putamen) dopamine correlated positively with WM capacity, whereas putamen (but not caudate) dopamine correlated positively with motor speed. In addition, delay-related fMRI activation in a left inferior prefrontal region was related to both caudate dopamine and task accuracy, suggesting that this may be a critical site for the integration of WM maintenance processes. These results provide new evidence that striatal dopaminergic function is related to PFC-dependent functions, particularly brain activation and behavioral performance during WM tasks.     

Distributed and associative working memory

This study explores the cortical cell dynamics of unimodal and cross-modal working memory (WM). Neuronal activity was recorded from parietal areas of monkeys performing delayed match-to-sample tasks with tactile or visual samples. Tactile memoranda (haptic samples) consisted of rods with differing surface features (texture or orientation of ridges) perceived by active touch. Visual memoranda (icons) consisted of striped patterns of differing orientation. In a haptic-haptic task, the animal had to retain through a period of delay the surface feature of the sample rod to select a rod that matched it. In a visual-haptic task, the animal had to retain the icon for the haptic choice of a rod with ridges of the same orientation as the icon's stripes. Units in all areas responded with firing change to one or more task events. Also in all areas, cells responded differently to different sample memoranda. Differential sample coherent firing was present in most areas during the memory period (delay). It is concluded that neurons in somatosensory and association areas of parietal cortex participate in broad networks that represent various task events and stimuli (auditory, motor, proprioceptive, tactile, and visual). Neurons in the same networks take part in retaining in WM the memorandum for each trial, whether it is encoded haptically or visually. The VH association by parietal cells in WM is analogous to the auditory-visual association previously observed in prefrontal cortex. Both illustrate the capacity of cortical neurons to associate sensory information across time and across modalities in accord with the rules of a behavioral task.     

Working memory of auditory localization

To investigate brain mechanisms of sound location memory, we studied the distribution of brain activation with functional magnetic resonance imaging (fMRI) in subjects performing an audiospatial n-back task with three memory load levels. Working memory processing of audiospatial information activated areas in the superior, middle and inferior frontal gyri, and in the posterior parietal and middle temporal cortices. In a control experiment, fMRI during audio- and visuospatial 2-back task performances revealed only few differentially activated subregions between the two tasks. These results demonstrate that working memory processing of auditory locations involves a distributed network of brain areas and suggest that mnemonic processing of audio- and visuospatial information is directed along a common neural pathway in the posterior parietal and prefrontal cortices.     

Population vector analysis of primate prefrontal activity during spatial working memory

Population vectors were used to examine information represented by a population of prefrontal activity and its temporal change during spatial working memory processes while monkeys performed ODR and R-ODR tasks. In the ODR task, monkeys made a saccade to the cue location after the delay, whereas in the R-ODR task, they made a saccade 90 degrees clockwise from the cue location. We first constructed population vectors using cue- and response-period activity. The directions of population vectors were similar to the cue directions and the saccade target directions, respectively, indicating that population vectors correctly represented information regarding directions of visual cues and saccade targets. We then calculated population vectors during a 250 ms time-window from the cue presentation to the end of the response period. In the ODR task, all population vectors were directed toward the cue direction. However, in the R-ODR task, the population vector gradually rotated during the delay period from the cue direction to the saccade direction. These results indicate that spatial information represented by a population of prefrontal activity can be shown as the direction of the population vector and that its temporal change during spatial working memory tasks can be depicted as the temporal change of the vector's direction.     

Interaction of working memory and long-term memory in the medial temporal lobe

Recent findings indicate that regions in the medial temporal lobe (MTL) do not only play a crucial role in long-term memory (LTM) encoding, but contribute to working memory (WM) as well. However, very few studies investigated the interaction between these processes so far. In a new functional magnetic resonance imaging paradigm comprising both a complex WM task and an LTM recognition task, we found not only that some items were successfully processed in WM but later forgotten, but also that a significant number of items which were not successfully processed in the WM task were subsequently recognized. Activation in the parahippocampal cortex (PHC) during successful WM was predictive of subsequent LTM, but was correlated with subsequent forgetting if the WM task was not successfully solved. The contribution of the PHC to LTM encoding thus crucially depends on whether an item was successfully processed in the WM task. Functional connectivity analysis revealed that across-trial fluctuations in PHC activity were correlated with activation in extensive regions if WM and LTM tasks were correctly solved, whereas connectivity broke down during unsuccessful attempts to do the task, suggesting that activity in the PHC during WM has to be well controlled to support LTM formation.     

Distinct neural circuits support transient and sustained processes in prospective memory and working memory

Current theories are divided as to whether prospective memory (PM) involves primarily sustained processes such as strategic monitoring, or transient processes such as the retrieval of intentions from memory when a relevant cue is encountered. The current study examined the neural correlates of PM using a functional magnetic resonance imaging design that allows for the decomposition of brain activity into sustained and transient components. Performance of the PM task was primarily associated with sustained responses in a network including anterior prefrontal cortex (lateral Brodmann area 10), and these responses were dissociable from sustained responses associated with active maintenance in working memory. Additionally, the sustained responses in anterior prefrontal cortex correlated with faster response times for prospective responses. Prospective cues also elicited selective transient activity in a region of interest along the right middle temporal gyrus. The results support the conclusion that both sustained and transient processes contribute to efficient PM and provide novel constraints on the functional role of anterior PFC in higher-order cognition.     

Attentional modulation of object representations in working memory

We investigated the role of object-based attention in modulating the maintenance of faces and scenes held online in working memory (WM). Participants had to remember a face and a scene, while cues presented during the delay instructed them to orient their attention to one or the other item. Event-related functional magnetic resonance imaging revealed that orienting attention in WM modulated the activity in fusiform and parahippocampal gyri, involved in maintaining representations of faces and scenes respectively. Measures from complementary behavioral studies indicated that this increase in activity corresponded to improved WM performance. The results show that directed attention can modulate maintenance of specific representations in WM, and help define the interplay between the domains of attention and WM.     

Dopaminergic modulation of auditory cortex-dependent memory consolidation through mTOR

Previous studies in the auditory cortex of Mongolian gerbils on discrimination learning of the direction of frequency-modulated tones (FMs) revealed that long-term memory formation involves activation of the dopaminergic system, activity of the protein kinase mammalian target of rapamycin (mTOR), and protein synthesis. This led to the hypothesis that the dopaminergic system might modulate memory formation via regulation of mTOR, which is implicated in translational control. Here, we report that the D1/D5 dopamine receptor agonist SKF-38393 substantially improved gerbils' FM discrimination learning when administered systemically or locally into the auditory cortex shortly before, shortly after, or 1 day before conditioning. Although acquisition performance during initial training was normal, the discrimination of FMs was enhanced during retraining performed hours or days after agonist injection compared with vehicle-injected controls. The D1/D5 receptor antagonist SCH-23390, the mTOR inhibitor rapamycin, and the protein synthesis blocker anisomycin suppressed this effect. By immunohistochemistry, D1 dopamine receptors were identified in the gerbil auditory cortex predominantly in the infragranular layers. Together, these findings suggest that in the gerbil auditory cortex dopaminergic inputs regulate mTOR-mediated, protein synthesis-dependent mechanisms, thus controlling for hours or days the consolidation of memory required for the discrimination of complex auditory stimuli.     

Dynamic cortical networks of verbal and spatial working memory: effects of memory load and task practice

Working memory (WM), the ability to briefly retain and manipulate information in mind, is central to intelligent behavior. Here we take advantage of the high temporal resolution of electrophysiological measures to obtain a millisecond timescale view of the activity induced in distributed cortical networks by tasks that impose significant WM demands. We examined how these networks are affected by the type and amount of information to be remembered, and by the amount of task practice. Evoked potentials (EPs) were obtained from eight subjects performing spatial and verbal versions of a visual n-back WM task (n = 1, 2, 3) on each of three testing days. In well-trained subjects, WM tasks elicited transient responses reflecting different subcomponents of task processing, including transient (lasting 0.02-0.3 s) task- sensitive and load-sensitive EPs, as well as sustained responses (lasting 1-1.5 s), including the prestimulus Contingent Negative Variation (CNV), and post-stimulus frontal and parietal Slow Waves. The transient responses, with the exception of the P300, differed between the verbal and spatial task versions, and between trials with different response requirements. The P300 and the Slow Waves were not affected by task version but were affected by increased WM load. These results suggest that WM emerges from the formation of a dynamic cortical network linking task-specific processes with non-specific, capacity- limited, higher-order attentional processes. Practice effects on the EPs suggested that practice led to the development of a more effective cognitive strategy for dealing with lower-order aspects of task processing, but did not diminish demands made on higher order processes. Thus a simple WM task is shown to be composed of numerous elementary subsecond neural processes whose characteristics vary with type and amount of information being remembered, and amount of practice.      

Kinesthetic working memory and action control within the dorsal stream

There is wide agreement that the "dorsal (action) stream" processes visual information for movement control. However, movements depend not only on vision but also on tactile and kinesthetic information (=haptics). Using functional magnetic resonance imaging, the present study investigates to what extent networks within the dorsal stream are also utilized for kinesthetic action control and whether they are also involved in kinesthetic working memory. Fourteen blindfolded participants performed a delayed-recognition task in which right-handed movements had to be encoded, maintained, and later recognized without any visual feedback. Encoding of hand movements activated somatosensory areas, superior parietal lobe (dorsodorsal stream), anterior intraparietal sulcus (aIPS) and adjoining areas (ventrodorsal stream), premotor cortex, and occipitotemporal cortex (ventral stream). Short-term maintenance of kinesthetic information elicited load-dependent activity in the aIPS and adjacent anterior portion of the superior parietal lobe (ventrodorsal stream) of the left hemisphere. We propose that the action representation system of the dorsodorsal and ventrodorsal stream is utilized not only for visual but also for kinesthetic action control. Moreover, the present findings demonstrate that networks within the ventrodorsal stream, in particular the left aIPS and closely adjacent areas, are also engaged in working memory maintenance of kinesthetic information.     

Functional MRI of working memory in paediatric head injury

A case study examining the recovery of a 9 year old boy who sustained a severe head injury is reported. The subject sustained damage to the left parietal-occipital and right frontal-parietal regions. Structural and functional imaging and cognitive data were collected at the time of injury and 1 year post-injury. Cognitive assessment revealed improvement over time. Functional imaging at the time of injury revealed minimal activation in the right posterior temporal region. Imaging 1 year post-injury revealed increased activation in the right pre-frontal cortex, bilateral pre-motor cortex and bilateral posterior parietal cortex. This activation pattern is consistent with the performance of unaffected individuals on working memory tasks. These findings differ from those in the adult literature and suggest an alternative pattern of recovery of function in children.     

Nonvisual codes and nonvisual brain areas support visual working memory

Systems models hold working memory to depend on specialized, domain-specific storage buffers. Here, however, we demonstrate that short-term retention of the identity or location of visually presented stimuli is disrupted by nonvisual secondary tasks performed in the dark-passive listening to nouns or endogenous generation of saccades, respectively. This indicates that the short-term retention of visual information relies on multiple mental codes, some of them nonvisual. Event-related functional magnetic resonance imaging (fMRI) reveals the neural correlates of these interference effects to be more complex and more regionally specific than previously described. Although nonspecific dual-task effects produce a generalized decrease of task-evoked fMRI response across many brain regions, the interference-specific effect is a relative increase of activity localized to regions associated with the secondary task in question: left hemisphere perisylvian cortex in the case of passive listening distraction and frontal oculomotor regions in the case of saccadic distraction. Within these regions, the neural interference effects are specific to voxels that show delay-period activity on unfilled memory trials. They also predict individual differences in the magnitude of the behavioral interference effect. These results indicate that nonvisual processes supported by nonvisual brain areas contribute importantly to "visual" working memory performance.     

Microstructure of frontoparietal connections predicts cortical responsivity and working memory performance

We investigated how the microstructure of relevant white matter connections is associated with cortical responsivity and working memory (WM) performance by collecting diffusion tensor imaging and verbal WM functional magnetic resonance imaging data from 29 young adults. We measured cortical responsivity within the frontoparietal WM network as the difference in blood oxygenation level-dependent (BOLD) signal between 3-back and 1-back conditions. Fractional anisotropy served as an index of the integrity of the superior longitudinal fasciculi (SLF), which connect frontal and posterior regions. We found that SLF integrity is associated with better 3-back performance and greater task-related BOLD responsivity. In addition, BOLD responsivity in right premotor cortex reliably mediated the effects of SLF integrity on 3-back performance but did not uniquely predict 3-back performance after controlling for individual differences in SLF integrity. Our results suggest that task-related adjustments of local gray matter processing are conditioned by the properties of anatomical connections between relevant cortical regions. We suggest that the microarchitecture of white matter tracts influences the speed of signal transduction along axons. This in turn may affect signal summation at neural dendrites, action potential firing, and the resulting BOLD signal change and responsivity.     

Rehabilitation of verbal working memory after left hemisphere stroke

PRIMARY OBJECTIVE: To assess a rehabilitation programme of working memory. RESEARCH DESIGN: Single case multiple-baseline-across-behaviour design in a patient with chronic stroke suffering from a specific impairment of working memory. METHODS: Rehabilitation included training of storage and processing components of verbal working memory. Outcome was assessed with specific working memory tests, non-specific tasks requiring working memory, non-target tasks not requiring working memory and questionnaires addressing daily-life functioning. This assessment was performed twice before the experimental therapy and once after. RESULTS: Cognitive measures were stable before therapy. A statistically significant improvement was found for target measures and for daily-life skills. In contrast, no change was found on non-target tasks. CONCLUSION: Improvement was not apparently related to spontaneous recovery, since performance was stable before therapy. This study suggests that specific cognitive training may improve working memory in patients with brain injury.