Discrimination task reveals differences in neural bases of tinnitus and hearing impairment

We investigated auditory perception and cognitive processing in individuals with chronic tinnitus or hearing loss using functional magnetic resonance imaging (fMRI). Our participants belonged to one of three groups: bilateral hearing loss and tinnitus (TIN), bilateral hearing loss without tinnitus (HL), and normal hearing without tinnitus (NH). We employed pure tones and frequency-modulated sweeps as stimuli in two tasks: passive listening and active discrimination. All subjects had normal hearing through 2 kHz and all stimuli were low-pass filtered at 2 kHz so that all participants could hear them equally well. Performance was similar among all three groups for the discrimination task. In all participants, a distributed set of brain regions including the primary and non-primary auditory cortices showed greater response for both tasks compared to rest. Comparing the groups directly, we found decreased activation in the parietal and frontal lobes in the participants with tinnitus compared to the HL group and decreased response in the frontal lobes relative to the NH group. Additionally, the HL subjects exhibited increased response in the anterior cingulate relative to the NH group. Our results suggest that a differential engagement of a putative auditory attention and short-term memory network, comprising regions in the frontal, parietal and temporal cortices and the anterior cingulate, may represent a key difference in the neural bases of chronic tinnitus accompanied by hearing loss relative to hearing loss alone.     

Brain Deactivation in the Outperformance in Bimodal Tasks: An fMRI Study

While it is known that some individuals can effectively perform two tasks simultaneously, other individuals cannot. How the brain deals with performing simultaneous tasks remains unclear. In the present study, we aimed to assess which brain areas corresponded to various phenomena in task performance. Nineteen subjects were requested to sequentially perform three blocks of tasks, including two unimodal tasks and one bimodal task. The unimodal tasks measured either visual feature binding or auditory pitch comparison, while the bimodal task required performance of the two tasks simultaneously. The functional magnetic resonance imaging (fMRI) results are compatible with previous studies showing that distinct brain areas, such as the visual cortices, frontal eye field (FEF), lateral parietal lobe (BA7), and medial and inferior frontal lobe, are involved in processing of visual unimodal tasks. In addition, the temporal lobes and Brodmann area 43 (BA43) were involved in processing of auditory unimodal tasks. These results lend support to concepts of modality-specific attention. Compared to the unimodal tasks, bimodal tasks required activation of additional brain areas. Furthermore, while deactivated brain areas were related to good performance in the bimodal task, these areas were not deactivated where the subject performed well in only one of the two simultaneous tasks. These results indicate that efficient information processing does not require some brain areas to be overly active; rather, the specific brain areas need to be relatively deactivated to remain alert and perform well on two tasks simultaneously. Meanwhile, it can also offer a neural basis for biofeedback in training courses, such as courses in how to perform multiple tasks simultaneously.     

Altered Resting-State Functional Connectivity of the Frontal-Striatal Reward System in Social Anxiety Disorder

We investigated differences in the intrinsic functional brain organization (functional connectivity) of the human reward system between healthy control participants and patients with social anxiety disorder. Functional connectivity was measured in the resting-state via functional magnetic resonance imaging (fMRI). 53 patients with social anxiety disorder and 33 healthy control participants underwent a 6-minute resting-state fMRI scan. Functional connectivity of the reward system was analyzed by calculating whole-brain temporal correlations with a bilateral nucleus accumbens seed and a ventromedial prefrontal cortex seed. Patients with social anxiety disorder, relative to the control group, had (1) decreased functional connectivity between the nucleus accumbens seed and other regions associated with reward, including ventromedial prefrontal cortex; (2) decreased functional connectivity between the ventromedial prefrontal cortex seed and lateral prefrontal regions, including the anterior and dorsolateral prefrontal cortices; and (3) increased functional connectivity between both the nucleus accumbens seed and the ventromedial prefrontal cortex seed with more posterior brain regions, including anterior cingulate cortex. Social anxiety disorder appears to be associated with widespread differences in the functional connectivity of the reward system, including markedly decreased functional connectivity between reward regions and between reward regions and lateral prefrontal cortices, and markedly increased functional connectivity between reward regions and posterior brain regions.     

Functional-anatomic correlates of individual differences in memory

Memory abilities differ greatly across individuals. To explore a source of these differences, we characterized the varied strategies people adopt during unconstrained encoding. Participants intentionally encoded object pairs during functional MRI. Principal components analysis applied to a strategy questionnaire revealed that participants variably used four main strategies to aid learning. Individuals' use of verbal elaboration and visual inspection strategies independently correlated with their memory performance. Verbal elaboration correlated with activity in a network of regions that included prefrontal regions associated with controlled verbal processing, while visual inspection correlated with activity in a network of regions that included an extrastriate region associated with object processing. Activity in regions associated with use of these strategies was also correlated with memory performance. This study reveals functional-anatomic correlates of verbal and perceptual strategies that are variably used by individuals during encoding. These strategies engage distinct brain regions and may separately influence memory performance.     

A model for integrating elementary neural functions into delayed-response behavior

It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning), and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task), or recalling from this image another one that has been associated with it during training (delayed-pair association task). The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.     

Longitudinal Neurostimulation in Older Adults Improves Working Memory

An increasing concern affecting a growing aging population is working memory (WM) decline. Consequently, there is great interest in improving or stabilizing WM, which drives expanded use of brain training exercises. Such regimens generally result in temporary WM benefits to the trained tasks but minimal transfer of benefit to untrained tasks. Pairing training with neurostimulation may stabilize or improve WM performance by enhancing plasticity and strengthening WM-related cortical networks. We tested this possibility in healthy older adults. Participants received 10 sessions of sham (control) or active (anodal, 1.5 mA) tDCS to the right prefrontal, parietal, or prefrontal/parietal (alternating) cortices. After ten minutes of sham or active tDCS, participants performed verbal and visual WM training tasks. On the first, tenth, and follow-up sessions, participants performed transfer WM tasks including the spatial 2-back, Stroop, and digit span tasks. The results demonstrated that all groups benefited from WM training, as expected. However, at follow-up 1-month after training ended, only the participants in the active tDCS groups maintained significant improvement. Importantly, this pattern was observed for both trained and transfer tasks. These results demonstrate that tDCS-linked WM training can provide long-term benefits in maintaining cognitive training benefits and extending them to untrained tasks.     

Face Patch Resting State Networks Link Face Processing to Social Cognition

Faces transmit a wealth of social information. How this information is exchanged between face-processing centers and brain areas supporting social cognition remains largely unclear. Here we identify these routes using resting state functional magnetic resonance imaging in macaque monkeys. We find that face areas functionally connect to specific regions within frontal, temporal, and parietal cortices, as well as subcortical structures supporting emotive, mnemonic, and cognitive functions. This establishes the existence of an extended face-recognition system in the macaque. Furthermore, the face patch resting state networks and the default mode network in monkeys show a pattern of overlap akin to that between the social brain and the default mode network in humans: this overlap specifically includes the posterior superior temporal sulcus, medial parietal, and dorsomedial prefrontal cortex, areas supporting high-level social cognition in humans. Together, these results reveal the embedding of face areas into larger brain networks and suggest that the resting state networks of the face patch system offer a new, easily accessible venue into the functional organization of the social brain and into the evolution of possibly uniquely human social skills.     

Learning related interactions among neuronal systems involved in memory processes

Functional neuroimaging techniques using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have provided new insights in our understanding of brain function from the molecular to the systems level. While subtraction strategy based data analyses have revealed the involvement of distributed brain regions in memory processes, covariance analysis based data analysis strategies allow functional interactions between brain regions of a neuronal network to be assessed. The focus of this chapter is to (1) establish the functional topography of episodic and working memory processes in young and old normal volunteers, (2) to assess functional interactions between modules of networks of brain regions by means of covariance based analyses and systems level modelling and (3) to relate neuroimaging data to the underpinning neural networks. Male normal young and old volunteers without neurological or psychiatric illness participated in neuroimaging studies (PET, fMRI) on working and episodic memory. Distributed brain areas are involved in memory processes (episodic and working memory) in young volunteers and show much of an overlap with respect to the network components. Systems level modelling analyses support the hypothesis of bihemispheric, asymmetric networks subserving memory processes and revealed both similarities in general and differences in the interactions between brain regions during episodic encoding and retrieval as well as working memory. Changes in memory function with ageing are evident from studies in old volunteers activating more brain regions compared to young volunteers and revealing more and stronger influences of prefrontal regions. We finally discuss the way in which the systems level models based on PET and fMRI results have implications for the understanding of the underlying neural network functioning of the brain.     

Neural synchrony during response production and inhibition

Inhibition of irrelevant information (conflict monitoring) and/or of prepotent actions is an essential component of adaptive self-organized behavior. Neural dynamics underlying these functions has been studied in humans using event-related brain potentials (ERPs) elicited in Go/NoGo tasks that require a speeded motor response to the Go stimuli and withholding a prepotent response when a NoGo stimulus is presented. However, averaged ERP waveforms provide only limited information about the neuronal mechanisms underlying stimulus processing, motor preparation, and response production or inhibition. In this study, we examine the cortical representation of conflict monitoring and response inhibition using time-frequency analysis of electroencephalographic (EEG) recordings during continuous performance Go/NoGo task in 50 young adult females. We hypothesized that response inhibition would be associated with a transient boost in both temporal and spatial synchronization of prefrontal cortical activity, consistent with the role of the anterior cingulate and lateral prefrontal cortices in cognitive control. Overall, phase synchronization across trials measured by Phase Locking Index and phase synchronization between electrode sites measured by Phase Coherence were the highest in the Go and NoGo conditions, intermediate in the Warning condition, and the lowest under Neutral condition. The NoGo condition was characterized by significantly higher fronto-central synchronization in the 300-600 ms window, whereas in the Go condition, delta- and theta-band synchronization was higher in centro-parietal regions in the first 300 ms after the stimulus onset. The present findings suggest that response production and inhibition is supported by dynamic functional networks characterized by distinct patterns of temporal and spatial synchronization of brain oscillations.     

Separating Recognition Processes of Declarative Memory via Anodal tDCS: Boosting Old Item Recognition by Temporal and New Item Detection by Parietal Stimulation

There is emerging evidence from imaging studies that parietal and temporal cortices act together to achieve successful recognition of declarative information; nevertheless, the precise role of these regions remains elusive. To evaluate the role of these brain areas in declarative memory retrieval, we applied bilateral tDCS, with anode over the left and cathode over the right parietal or temporal cortices separately, during the recognition phase of a verbal learning paradigm using a balanced old-new decision task. In a parallel group design, we tested three different groups of healthy adults, matched for demographic and neurocognitive status: two groups received bilateral active stimulation of either the parietal or the temporal cortex, while a third group received sham stimulation. Accuracy, discriminability index (d’) and reaction times of recognition memory performance were measurements of interest. The d’ sensitivity index and accuracy percentage improved in both active stimulation groups, as compared with the sham one, while reaction times remained unaffected. Moreover, the analysis of accuracy revealed a different effect of tDCS for old and new item recognition. While the temporal group showed enhanced performance for old item recognition, the parietal group was better at correctly recognising new ones. Our results support an active role of both of these areas in memory retrieval, possibly underpinning different stages of the recognition process.     

Characteristics of the parietal cortex activation in humans during different attention tasks

The cortical activation was estimated by the event-related potential (ERPs) methods during selection tasks of lateralized visual stimuli requiring different forms of attention: 1) form of stimuli, 2) stimuli position, 3) combined attention of form and position. The ERPs were recorded in 15 young healthy adults in 6 leads P3, P4, T3, T4, T5, T6, and endogenous ERPs components: CNV (contingent negative variation), N1, P3 and the complex [N1-P3]. Differences between the ERPs at "attended" and "non-attended" stimuli were considered as indices of selection attention of particular feature of visual stimuli. Such indices of form and position were revealed selectivity in parietal leads. The most eminent ERPs components, the pronounced activation gradient during increase of attention demands were revealed in parietal regions (vs. temporal ones). In our opinion, parietal cortex has a high priority in selection attention system.     

Effects of aversive stimuli on prospective memory. An event-related fMRI study

Prospective memory (PM) describes the ability to execute a previously planned action at the appropriate point in time. Although behavioral studies clearly showed that prospective memory performance is affected by the emotional significance attributed to the intended action, no study so far investigated the brain mechanisms subserving the modulatory effect of emotional salience on PM performance. The general aim of the present study was to explore brain regions involved in prospective memory processes when PM cues are associated with emotional stimuli. In particular, based on the hypothesised critical role of the prefrontal cortex in prospective memory in the presence of emotionally salient stimuli, we expected a stronger involvement of aPFC when the retrieval and execution of the intended action is cued by an aversive stimulus. To this aim BOLD responses of PM trials cued by aversive facial expressions were compared to PM trials cued by neutral facial expressions. Whole brain analysis showed that PM task cued by aversive stimuli is differentially associated with activity in the right lateral prefrontal area (BA 10) and in the left caudate nucleus. Moreover a temporal shift between the response of the caudate nucleus that preceded that of aPFC was observed. These findings suggest that the caudate nucleus might provide an early analysis of the affective properties of the stimuli, whereas the anterior lateral prefrontal cortex (BA10) would be involved in a slower and more deliberative analysis to guide goal-directed behaviour.     

Sound facilitates visual learning

Numerous studies show that practice can result in performance improvements on low-level visual perceptual tasks [1-5]. However, such learning is characteristically difficult and slow, requiring many days of training [6-8]. Here, we show that a multisensory audiovisual training procedure facilitates visual learning and results in significantly faster learning than unisensory visual training. We trained one group of subjects with an audiovisual motion-detection task and a second group with a visual motion-detection task, and compared performance on trials containing only visual signals across ten days of training. Whereas observers in both groups showed improvements of visual sensitivity with training, subjects trained with multisensory stimuli showed significantly more learning both within and across training sessions. These benefits of multisensory training are particularly surprising given that the learning of visual motion stimuli is generally thought to be mediated by low-level visual brain areas [6, 9, 10]. Although crossmodal interactions are ubiquitous in human perceptual processing [11-13], the contribution of crossmodal information to perceptual learning has not been studied previously. Our results show that multisensory interactions can be exploited to yield more efficient learning of sensory information and suggest that multisensory training programs would be most effective for the acquisition of new skills.     

Structural and Functional Brain Alterations in End Stage Renal Disease Patients on Routine Hemodialysis: A Voxel-Based Morphometry and Resting State Functional Connectivity Study

Background and Purpose

Cognitive impairment is a well-described phenomenon in end-stage renal disease (ESRD) patients. However, its pathogenesis remains poorly understood. The primary focus of this study was to examine structural and functional brain deficits in ESRD patients.

Materials and Methods

Thirty ESRD patients on hemodialysis (without clinical neurological disease) and 30 age- and gender-matched control individuals (without renal or neurological problems) were recruited in a prospective, single-center study. High-resolution structural magnetic resonance imaging (MRI) and resting state functional MRI were performed on both groups to detect the subtle cerebral deficits in ESRD patients. Voxel-based morphometry was used to characterize gray matter deficits in ESRD patients. The impact of abnormal morphometry on the cerebral functional integrity was investigated by evaluating the alterations in resting state functional connectivity when brain regions with gray matter volume reduction were used as seed areas.

Results

A significant decrease in gray matter volume was observed in ESRD patients in the bilateral medial orbito-prefrontal cortices, bilateral dorsal lateral prefrontal cortices, and the left middle temporal cortex. When brain regions with gray matter volume reduction were used as seed areas, the integration was found to be significantly decreased in ESRD patients in the fronto-cerebellum circuits and within prefrontal circuits. In addition, significantly enhanced functional connectivity was found between the prefrontal cortex and the left temporal cortex and within the prefrontal circuits.

Conclusions

Our study revealed that both the structural and functional cerebral cortices were impaired in ESRD patients on routine hemodialysis.     

Origins of spatial working memory deficits in schizophrenia: an event-related FMRI and near-infrared spectroscopy study

Abnormal prefrontal functioning plays a central role in the working memory (WM) deficits of schizophrenic patients, but the nature of the relationship between WM and prefrontal activation remains undetermined. Using two functional neuroimaging methods, we investigated the neural correlates of remembering and forgetting in schizophrenic and healthy participants. We focused on the brain activation during WM maintenance phase with event-related functional magnetic resonance imaging (fMRI). We also examined oxygenated hemoglobin changes in relation to memory performance with the near-infrared spectroscopy (NIRS) using the same spatial WM task. Distinct types of correct and error trials were segregated for analysis. fMRI data indicated that prefrontal activation was increased during WM maintenance on correct trials in both schizophrenic and healthy subjects. However, a significant difference was observed in the functional asymmetry of frontal activation pattern. Healthy subjects showed increased activation in the right frontal, temporal and cingulate regions. Schizophrenic patients showed greater activation compared with control subjects in left frontal, temporal and parietal regions as well as in right frontal regions. We also observed increased 'false memory' errors in schizophrenic patients, associated with increased prefrontal activation and resembling the activation pattern observed on the correct trials. NIRS data replicated the fMRI results. Thus, increased frontal activity was correlated with the accuracy of WM in both healthy control and schizophrenic participants. The major difference between the two groups concerned functional asymmetry; healthy subjects recruited right frontal regions during spatial WM maintenance whereas schizophrenic subjects recruited a wider network in both hemispheres to achieve the same level of memory performance. Increased "false memory" errors and accompanying bilateral prefrontal activation in schizophrenia suggest that the etiology of memory errors must be considered when comparing group performances. Finally, the concordance of fMRI and NIRS data supports NIRS as an alternative functional neuroimaging method for psychiatric research.     

Cognitive Control in Auditory Working Memory Is Enhanced in Musicians

Musical competence may confer cognitive advantages that extend beyond processing of familiar musical sounds. Behavioural evidence indicates a general enhancement of both working memory and attention in musicians. It is possible that musicians, due to their training, are better able to maintain focus on task-relevant stimuli, a skill which is crucial to working memory. We measured the blood oxygenation-level dependent (BOLD) activation signal in musicians and non-musicians during working memory of musical sounds to determine the relation among performance, musical competence and generally enhanced cognition. All participants easily distinguished the stimuli. We tested the hypothesis that musicians nonetheless would perform better, and that differential brain activity would mainly be present in cortical areas involved in cognitive control such as the lateral prefrontal cortex. The musicians performed better as reflected in reaction times and error rates. Musicians also had larger BOLD responses than non-musicians in neuronal networks that sustain attention and cognitive control, including regions of the lateral prefrontal cortex, lateral parietal cortex, insula, and putamen in the right hemisphere, and bilaterally in the posterior dorsal prefrontal cortex and anterior cingulate gyrus. The relationship between the task performance and the magnitude of the BOLD response was more positive in musicians than in non-musicians, particularly during the most difficult working memory task. The results confirm previous findings that neural activity increases during enhanced working memory performance. The results also suggest that superior working memory task performance in musicians rely on an enhanced ability to exert sustained cognitive control. This cognitive benefit in musicians may be a consequence of focused musical training.     

Perceptual classification in a rapidly changing environment

Humans and monkeys can learn to classify perceptual information in a statistically optimal fashion if the functional groupings remain stable over many hundreds of trials, but little is known about categorization when the environment changes rapidly. Here, we used a combination of computational modeling and functional neuroimaging to understand how humans classify visual stimuli drawn from categories whose mean and variance jumped unpredictably. Models based on optimal learning (Bayesian model) and a cognitive strategy (working memory model) both explained unique variance in choice, reaction time, and brain activity. However, the working memory model was the best predictor of performance in volatile environments, whereas statistically optimal performance emerged in periods of relative stability. Bayesian and working memory models predicted decision-related activity in distinct regions of the prefrontal cortex and midbrain. These findings suggest that perceptual category judgments, like value-guided choices, may be guided by multiple controllers.     

Neocortical connectivity during episodic memory formation

During the formation of new episodic memories, a rich array of perceptual information is bound together for long-term storage. However, the brain mechanisms by which sensory representations (such as colors, objects, or individuals) are selected for episodic encoding are currently unknown. We describe a functional magnetic resonance imaging experiment in which participants encoded the association between two classes of visual stimuli that elicit selective responses in the extrastriate visual cortex (faces and houses). Using connectivity analyses, we show that correlation in the hemodynamic signal between face- and place-sensitive voxels and the left dorsolateral prefrontal cortex is a reliable predictor of successful face-house binding. These data support the view that during episodic encoding, "top-down" control signals originating in the prefrontal cortex help determine which perceptual information is fated to be bound into the new episodic memory trace.     

Trait anxiety and neural efficiency of abstract reasoning: An fMRI investigation

Worries preoccupy the working memory capacity in anxious individuals, thereby affecting their performance during tasks that require efficient attention regulation. According to the attentional control theory (ACT), trait anxiety affects the processing efficiency, i.e. the effort required for task performance, more than the accuracy of task performance. We investigated the relation between trait anxiety and neural response for a reasoning task in healthy subjects. Functional magnetic resonance imaging (fMRI) was carried out on 22 healthy participants and blood oxygenation level dependent (BOLD) contrast estimates were extracted from a priori regions of interest (ROIs) that were earlier implicated in reasoning (i.e., bilaterally caudate head, globus pallidus, thalamus, prefrontal cortex [rostral, dorsal and ventral regions], inferior parietal lobule and middle occipital gyrus). Controlling for the effects of age, gender, state anxiety and depressive symptoms, for equivalent levels of task performance, trait anxiety of the participants was found to be associated with an increase in task related BOLD activation in right globus pallidus, left thalamus and left middle occipital gyrus. Our results suggest a reduced processing efficiency for reasoning in high trait anxiety subjects and provides important brain–behaviour relationships with respect to sub-clinical anxiety.     

Form and motion coherence activate independent, but not dorsal/ventral segregated, networks in the human brain

There is much evidence in primates' visual processing for distinct mechanisms involved in object recognition and encoding object position and motion, which have been identified with 'ventral' and 'dorsal' streams, respectively, of the extra-striate visual areas [1] [2] [3]. This distinction may yield insights into normal human perception, its development and pathology. Motion coherence sensitivity has been taken as a test of global processing in the dorsal stream [4] [5]. We have proposed an analogous 'form coherence' measure of global processing in the ventral stream [6]. In a functional magnetic resonance imaging (fMRI) experiment, we found that the cortical regions activated by form coherence did not overlap with those activated by motion coherence in the same individuals. Areas differentially activated by form coherence included regions in the middle occipital gyrus, the ventral occipital surface, the intraparietal sulcus, and the temporal lobe. Motion coherence activated areas consistent with those previously identified as V5 and V3a, the ventral occipital surface, the intraparietal sulcus, and temporal structures. Neither form nor motion coherence activated area V1 differentially. Form and motion foci in occipital, parietal, and temporal areas were nearby but showed almost no overlap. These results support the idea that form and motion coherence test distinct functional brain systems, but that these do not necessarily correspond to a gross anatomical separation of dorsal and ventral processing streams.