Distinct causal influences of parietal versus frontal areas on human visual cortex: evidence from concurrent TMS-fMRI

It has often been proposed that regions of the human parietal and/or frontal lobe may modulate activity in visual cortex, for example, during selective attention or saccade preparation. However, direct evidence for such causal claims is largely missing in human studies, and it remains unclear to what degree the putative roles of parietal and frontal regions in modulating visual cortex may differ. Here we used transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) concurrently, to show that stimulating right human intraparietal sulcus (IPS, at a site previously implicated in attention) elicits a pattern of activity changes in visual cortex that strongly depends on current visual context. Increased intensity of IPS TMS affected the blood oxygen level-dependent (BOLD) signal in V5/MT+ only when moving stimuli were present to drive this visual region, whereas TMS-elicited BOLD signal changes were observed in areas V1-V4 only during the absence of visual input. These influences of IPS TMS upon remote visual cortex differed significantly from corresponding effects of frontal (eye field) TMS, in terms of how they related to current visual input and their spatial topography for retinotopic areas V1-V4. Our results show directly that parietal and frontal regions can indeed have distinct patterns of causal influence upon functional activity in human visual cortex.     

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.     

The neural basis of visual skill learning: an fMRI study of mirror reading

The learning of perceptual skills is thought to rely upon multiple regions in the cerebral cortex, but imaging studies have not yet provided evidence about the changes in neural activity that accompany visual skill learning. Functional magnetic resonance imaging (fMRI) was used to examine changes in activation of posterior brain regions associated with the acquisition of mirror-reading skill for novel and practiced stimuli. Multiple regions in the occipital lobe, inferior temporal cortex, superior parietal cortex and cerebellum were involved in the reading of mirror-reversed compared to normally oriented text. For novel stimuli, skilled mirror-reading was associated with decreased activation in the right superior parietal cortex and posterior occipital regions and increased activation in the left inferior temporal lobe. These results suggest that learning to read mirror- reversed text involves a progression from visuospatial transformation to direct recognition of transformed letters. Reading practiced, relative to unpracticed, stimuli was associated with decreased activation in occipital visual cortices, inferior temporal cortex and superior parietal cortex and increased activation in occipito-parietal and lateral temporal regions. By examining skill learning and item- specific repetition priming in the same task, this study demonstrates that both of these forms of learning exhibit shifts in the set of neural structures that contribute to performance.      

Cortical network for gaze control in humans revealed using multimodal MRI

Functional magnetic resonance imaging (fMRI) techniques allow definition of cortical nodes that are presumed to be components of large-scale distributed brain networks involved in cognitive processes. However, very few investigations examine whether such functionally defined areas are in fact structurally connected. Here, we used combined fMRI and diffusion MRI-based tractography to define the cortical network involved in saccadic eye movement control in humans. The results of this multimodal imaging approach demonstrate white matter pathways connecting the frontal eye fields and supplementary eye fields, consistent with the known connectivity of these regions in macaque monkeys. Importantly, however, these connections appeared to be more prominent in the right hemisphere of humans. In addition, there was evidence of a dorsal frontoparietal pathway connecting the frontal eye field and the inferior parietal lobe, also right hemisphere dominant, consistent with specialization of the right hemisphere for directed attention in humans. These findings demonstrate the utility and potential of using multimodal imaging techniques to define large-scale distributed brain networks, including those that demonstrate known hemispheric asymmetries in humans.     

Frontoparietal network involved in successful retrieval from episodic memory. Spatial and temporal analyses using fMRI and ERP

The neural basis for successful recognition of previously studied items, referred to as "retrieval success," has been investigated using either neuroimaging or brain potentials; however, few studies have used both modalities. Our study combined event-related functional magnetic resonance imaging (fMRI) and event-related potential (ERP) in separate groups of subjects. The neural responses were measured while the subjects performed an old/new recognition task with pictures that had been previously studied in either a deep- or shallow-encoding condition. The fMRI experiment showed that among the frontoparietal regions involved in retrieval success, the inferior frontal gyrus and intraparietal sulcus were crucial to conscious recollection because the activity of these regions was influenced by the depth of memory at encoding. The activity of the right parietal region in response to a repeated item was modulated by the repetition lag, indicating that this area would be critical to familiarity-based judgment. The results of structural equation modeling revealed that the functional connectivity among the regions in the left hemisphere was more significant than that in the right hemisphere. The results of the ERP experiment and independent component analysis paralleled those of the fMRI experiment and demonstrated that the repeated item produced an earlier peak than the hit item by approximately 50 ms.     

Control of object-based attention in human cortex

Visual attention is a mechanism by which observers select relevant or important information from the current visual array. Previous investigations have focused primarily on the ability to select a region of space for further visual analysis. These studies have revealed a distributed frontoparietal circuit that is responsible for the control of spatial attention. However, vision must ultimately represent objects and in real scenes objects often overlap spatially; thus attention must be capable of selecting objects and their properties nonspatially. Little is known about the neural basis of object-based attentional control. In two experiments, human observers shifted attention between spatially superimposed faces and houses. Event-related functional magnetic resonance imaging (fMRI) revealed attentional modulation of activity in face- and house-selective cortical regions. Posterior parietal and frontal regions were transiently active when attention was shifted between spatially superimposed perceptual objects. The timecourse of activity provides insight into the functional role that these brain regions play in attentional control processes.     

Right parietal cortex plays a critical role in change blindness

There is increasing evidence from functional magnetic resonance imaging (fMRI) that visual awareness is not only associated with activity in ventral visual cortex but also with activity in the parietal cortex. However, due to the correlational nature of neuroimaging, it remains unclear whether this parietal activity plays a causal role in awareness. In the experiment presented here we disrupted activity in right or left parietal cortex by applying repetitive transcranial magnetic stimulation (rTMS) over these areas while subjects attempted to detect changes between two images separated by a brief interval (i.e. 1-shot change detection task). We found that rTMS applied over right parietal cortex but not left parietal cortex resulted in longer latencies to detect changes and a greater rate of change blindness compared with no TMS. These results suggest that the right parietal cortex plays a critical role in conscious change detection.     

Thinking about actions: the neural substrates of person knowledge

Despite an extensive literature on the neural substrates of semantic knowledge, how person-related information is represented in the brain has yet to be elucidated. Accordingly, in the present study we used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of person knowledge. Focusing on the neural substrates of action knowledge, participants reported whether or not a common set of behaviors could be performed by people or dogs. While dogs and people are capable of performing many of the same actions (e.g. run, sit, bite), we surmised that the representation of this knowledge would be associated with distinct patterns of neural activity. Specifically, person judgments were expected to activate cortical areas associated with theory of mind (ToM) reasoning. The results supported this prediction. Whereas action-related judgments about dogs were associated with activity in various regions, including the occipital and parahippocampal gyri; identical judgments about people yielded activity in areas of prefrontal cortex, notably the right middle and medial frontal gyri. These findings suggest that person knowledge may be functionally dissociable from comparable information about other animals, with action-related judgments about people recruiting neural activity that is indicative of ToM reasoning.     

Speaking of which: dissecting the neurocognitive network of language production in picture naming

The noninvasive methods of cognitive neuroscience offer new possibilities to study language. We used neuronavigated multisite transcranial magnetic stimulation (TMS) to determine the functional relevance of 1) the posterior part of left superior temporal gyrus (Wernicke's area), 2) a midportion of Broca's area (slightly posterior/superior to apex of vertical ascending ramus), and 3) the midsection of the left middle temporal gyrus (MTG), during overt picture naming. Our chronometric TMS design enabled us to chart the time points at which neural activity in each of these regions functionally contributes to overt speech production. Our findings demonstrate that the midsection of left MTG becomes functionally relevant at 225 ms after picture onset, followed by Broca's area at 300 ms and Wernicke's area at 400 ms. Interestingly, during this late time window, the left MTG shows a second peak of functional relevance. Each area thus contributed during the speech production process at different stages, suggesting distinct underlying functional roles within this complex multicomponential skill. These findings are discussed and framed in the context of psycholinguistic models of speech production according to which successful speaking relies on intact, spatiotemporally specific feed forward and recurrent feedback loops within a left-hemispheric fronto-temporal brain connectivity network.     

Controlling emotional expression: behavioral and neural correlates of nonimitative emotional responses

Emotional facial expressions can engender similar expressions in others. However, adaptive social and motivational behavior can require individuals to suppress, conceal, or override prepotent imitative responses. We predicted, in line with a theory of "emotion contagion," that when viewing a facial expression, expressing a different emotion would manifest as behavioral conflict and interference. We employed facial electromyography (EMG) and functional magnetic resonance imaging (fMRI) to investigate brain activity related to this emotion expression interference (EEI) effect, where the expressed response was either concordant or discordant with the observed emotion. The Simon task was included as a nonemotional comparison for the fMRI study. Facilitation and interference effects were observed in the latency of facial EMG responses. Neuroimaging revealed activation of distributed brain regions including anterior right inferior frontal gyrus (brain area [BA] 47), supplementary motor area (facial area), posterior superior temporal sulcus (STS), and right anterior insula during emotion expression-associated interference. In contrast, nonemotional response conflict (Simon task) engaged a distinct frontostriatal network. Individual differences in empathy and emotion regulatory tendency predicted the magnitude of EEI-evoked regional activity with BA 47 and STS. Our findings point to these regions as providing a putative neural substrate underpinning a crucial adaptive aspect of social/emotional behavior.     

Similar frontal and distinct posterior cortical regions mediate visual and auditory perceptual awareness

Activity in ventral visual cortex is a consistent neural correlate of visual consciousness. However, activity in this area seems insufficient to produce awareness without additional involvement of frontoparietal regions. To test the generality of the frontoparietal response, neural correlates of auditory awareness were investigated in a paradigm that previously has revealed frontoparietal activity during conscious visual perception. A within-experiment comparison showed that frontal regions were related to both visual and auditory awareness, whereas parietal activity was correlated with visual awareness and superior temporal activity with auditory awareness. These results indicate that frontal regions interact with specific posterior regions to produce awareness in different sensory modalities.     

FEF TMS affects visual cortical activity

We tested whether the frontal eye field (FEF) is critical in controlling visual processing in posterior visual brain areas during the orienting of spatial attention. Short trains (5 pulses at 10 Hz) of transcranial magnetic stimulation (TMS) were applied to the right FEF during the cueing period of a covert attentional task while event-related potentials (ERPs) were simultaneously recorded from lateral posterior electrodes, where visual components are prominent. FEF TMS significantly affected the neural activity evoked by visual stimuli, as well as the ongoing neural activity recorded during earlier anticipation of the visual stimuli. The effects of FEF TMS started earlier and were greatest for brain activity recorded ipsilaterally to FEF TMS and contralaterally to the visual stimulus. The TMS-induced effect on visual ERPs occurred at the same time as ERPs were shown to be modulated by visual attention. Importantly, no similar effects were observed after TMS of a control site that was physically closer but not anatomically interconnected to the recording sites. The results show that the human FEF has a causal influence over the modulation of visual activity in posterior areas when attention is being allocated.     

Pre-surgical cortical activation to food pictures is associated with weight loss following bariatric surgery

BackgroundRecent research suggests that preintervention functional magnetic resonance imaging (fMRI) data may predict weight loss outcomes among patients who participate in a behavioral weight loss plan. No study has examined whether presurgical brain activation can predict outcomes following bariatric surgery.MethodThe aim of the present study was to determine if brain activations during a presurgical fMRI food-motivation paradigm are associated with weight loss 3 and 6 months following laparoscopic adjustable gastric banding (LAGB). Nineteen participants viewed food and nonfood pictures from a well-established food motivation paradigm during an fMRI scanning session before LAGB surgery. Weight was assessed presurgery and 3 and 6 months postsurgery; data for all participants was available at each time point. fMRI data were analyzed using the BrainVoyager QX statistical package. Whole brain voxelwise correlations of presurgery (food–nonfood) brain activation and weight, corrected for multiple comparisons, were performed to analyze the relationship between presurgical brain activation and subsequent weight loss. The settings were a medical university brain imaging center and 2 surgical weight loss centers in a major metropolitan area.ResultsIncreased activity in frontal regions associated with cognitive control (medial, middle, superior frontal gyrus) and posterior cingulate cortex was associated with weight loss following LAGB.ConclusionWe found that neural activity in previously established regions associated with cognitive and behavioral self-regulation predicts weight loss following bariatric surgery. These preliminary findings highlight the role of neural circuitry in the success and maintenance of weight loss and suggest a possible future use of fMRI in screening LAGB surgery candidates.     

Repetitive transcranial magnetic stimulation effects on brain function and cognition among elders with memory dysfunction. A randomized sham-controlled study

In the present study, we aimed to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on memory performance and brain activity in elders presenting with subjective memory complaints and a memory performance within the low normal range. Forty participants underwent 2 functional magnetic resonance imaging (fMRI) sessions, in which they were administered 2 equivalent face-name memory tasks. Following each fMRI, subjects were asked to pair faces with their corresponding proper name. In-between, high-frequency rTMS was applied randomly using real or sham stimulation in a double-blind design. Only subjects who received active rTMS improved in associative memory significantly. This was accompanied by additional recruitment of right prefrontal and bilaterial posterior cortical regions at the second fMRI session, relative to baseline scanning. Our findings reflect a potentiality of rTMS to recruit compensatory networks, which participate during the memory-encoding process. Present results represent the first evidence that rTMS is capable of transitorily and positively influencing brain function and cognition among elders with memory complaints.     

Mathematics anxiety: separating the math from the anxiety

Anxiety about math is tied to low math grades and standardized test scores, yet not all math-anxious individuals perform equally poorly in math. We used functional magnetic resonance imaging to separate neural activity during the anticipation of doing math from activity during math performance itself. For higher (but not lower) math-anxious individuals, increased activity in frontoparietal regions when simply anticipating doing math mitigated math-specific performance deficits. This network included bilateral inferior frontal junction, a region involved in cognitive control and reappraisal of negative emotional responses. Furthermore, the relation between frontoparietal anticipatory activity and highly math-anxious individuals' math deficits was fully mediated (or accounted for) by activity in caudate, nucleus accumbens, and hippocampus during math performance. These subcortical regions are important for coordinating task demands and motivational factors during skill execution. Individual differences in how math-anxious individuals recruit cognitive control resources prior to doing math and motivational resources during math performance predict the extent of their math deficits. This work suggests that educational interventions emphasizing control of negative emotional responses to math stimuli (rather than merely additional math training) will be most effective in revealing a population of mathematically competent individuals, who might otherwise go undiscovered.     

Sensitivity of the action observation network to physical and observational learning

Human motor skills can be acquired by observation without the benefit of immediate physical practice. The current study tested if physical rehearsal and observational learning share common neural substrates within an action observation network (AON) including premotor and inferior parietal regions, that is, areas activated both for execution and observation of similar actions. Participants trained for 5 days on dance sequences set to music videos. Each day they physically rehearsed one set of dance sequences ("danced"), and passively watched a different set of sequences ("watched"). Functional magnetic resonance imaging was obtained prior to and immediately following the 5 days of training. After training, a subset of the AON showed a degree of common activity for observational and physical learning. Activity in these premotor and parietal regions was sustained during observation of sequences that were danced or watched, but declined for unfamiliar sequences relative to the pretraining scan session. These imaging data demonstrate the emergence of action resonance processes in the human brain based on observational learning without physical practice and identify commonalities in the neural substrates for physical and observational learning.     

Symptoms of Posttraumatic Stress Disorder are Associated with Exaggerated Neural Response to Surprising Errors

Posttraumatic stress disorder (PTSD) is characterized by exaggerated salience of previously innocuous cues and associated with hyperactivity of salience‐related brain regions. Recently, computational models have been deployed to operationalize salience more precisely regarding surprise‐driven learning, leading to findings that such learning is altered in anxiety‐related disorders. In the present study, a sample of 20 combat veterans completed a probabilistic learning task during fMRI scanning. We applied a computational model to generate a trial‐by‐trial surprise signal (i.e., unsigned prediction error or difference between the expected probability of an outcome and the actual observed outcome), which allowed us to examine the neural response to surprising events. We did not observe an association between PTSD symptoms and behavioral indices of learning in the task. Surprising errors were associated with increased activity in the left precuneus/inferior parietal lobule and right inferior parietal lobule, two parietal regions that are linked to salience processing. Additionally, PTSD symptom severity was positively associated with precuneus/inferior parietal lobule activation to surprising errors, r = .63, p = .004. Taken together, this pattern of results suggests that PTSD symptoms are specifically associated with an exaggerated response to surprising errors in salience‐related regions of the brain. This altered pattern of neural activity could represent a target for intervention to improve PTSD symptoms.     

Transcranial magnetic stimulation in brain injury

Objectives

Transcranial magnetic stimulations (TMS) have been used for many years as a diagnostic tool to explore changes in cortical excitability, and more recently as a tool for therapeutic neuromodulation. We are interested in their applications following brain injury: stroke, traumatic and anoxic brain injury.

Data synthesis

Following brain injury, there is decreased cortical excitability and changes in interhemispheric interactions depending on the type, the severity, and the time-lapse between the injury and the treatment implemented. rTMS (repetitive TMS) is a therapeutic neuromodulation tool which restores the interhemispheric interactions following stroke by inhibiting the healthy cortex with frequencies ≤ 1 Hz, or by exciting the lesioned cortex with frequencies between 3 and 50 Hz. Results in motor recovery are promising and those in improving aphasia or visuospatial neglect are also encouraging. Finally, the use of TMS is mainly limited by the risk of seizure, and is therefore contraindicated for many patients.

Conclusion

TMS is a useful non-invasive brain stimulation tool to diagnose the effects of brain injury, to study the mechanisms of recovery and a non-invasive neuromodulation promising tool to influence the post-lesional recovery.     

Learning shapes spatiotemporal brain patterns for flexible categorical decisions

Learning is thought to facilitate our ability to perform complex perceptual tasks and optimize brain circuits involved in decision making. However, little is known about the experience-dependent mechanisms in the human brain that support our ability to make fine categorical judgments. Previous work has focused on identifying spatial brain patterns (i.e., areas) that change with learning. Here, we take advantage of the complementary high spatial and temporal resolution of simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) to identify the spatiotemporal dynamics between cortical networks involved in flexible category learning. Observers were trained to use different decision criteria (i.e., category boundaries) when making fine categorical judgments on morphed stimuli (i.e., radial vs. concentric patterns). Our findings demonstrate that learning acts on a feedback-based circuit that supports fine categorical judgments. Experience-dependent changes in the behavioral decision criterion were associated with changes in later perceptual processes engaging higher occipitotemporal and frontoparietal circuits. In contrast, category learning did not modulate early processes in a medial frontotemporal network that are thought to support the coarse interpretation of visual scenes. These findings provide evidence that learning flexible criteria for fine categorical judgments acts on distinct spatiotemporal brain circuits and shapes the readout of sensory signals that provide evidence for categorical decisions.     

Remediation of sleep-deprivation-induced working memory impairment with fMRI-guided transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) was applied to test the role of selected cortical regions in remediating sleep-deprivation-induced deficits in visual working memory (WM) performance. Three rTMS targets were chosen using a functional magnetic resonance imaging (fMRI)-identified network associated with sleep-deprivation-induced WM performance impairment: 2 regions from the network (upper left middle occipital gyrus and midline parietal cortex) and 1 nonnetwork region (lower left middle occipital gyrus). Fifteen participants underwent total sleep deprivation for 48 h. rTMS was applied at 5 Hz during a WM task in a within-subject sham-controlled design. The rTMS to the upper-middle occipital site resulted in a reduction of the sleep-induced reaction time deficit without a corresponding decrease in accuracy, whereas stimulation at the other sites did not. Each subject had undergone fMRI scanning while performing the task both pre- and postsleep deprivation, and the degree to which each individual activated the fMRI network was measured. The degree of performance enhancement with upper-middle occipital rTMS correlated with the degree to which each individual failed to sustain network activation. No effects were found in a subset of participants who performed the same rTMS procedure after recovering from sleep deprivation, suggesting that the performance enhancements seen following sleep deprivation were state dependent.