Task demand modulations of visuospatial processing measured with functional magnetic resonance imaging

Brain imaging based on functional magnetic resonance imaging (fMRI) provides a useful tool to examine neural networks and cerebral structures subserving visuospatial function. It allows not only the qualitative determination of which areas are active during task processing, but also estimates the quantitative contribution of involved brain regions to different aspects of spatial processing. In this study, we investigated in 10 healthy subjects how the amount of task (computational) demand in an angle discrimination task was related to neural activity as measured with event-related fMRI. Task demand, indicated by behavioral performance, was modulated by presenting clocks with different angular disparity and length of hands. Significant activations were found in the cortical network subserving the visual and visuospatial processing, including the right and left superior parietal lobules (SPL), striate visual areas, and sensorimotor areas. Both blood oxygenation level-dependent (BOLD) signal strength and spatial extent of activation in right as well as left SPL increased with task demand. By contrast, no significant correlation or a very weak correlation was found between the task demand and the BOLD signal as well as between task demand and spatial extent of activations in the striate visual areas and in the sensorimotor areas. These results support the hypothesis that increased computational demand requires more brain resources. The brain regions that are most specialized for the execution of the visuospatial task can be assessed by relating the imposed task demand to the functional activation measured.     

Sensitivity to orthographic familiarity in the occipito-temporal region

The involvement of the left hemisphere occipito-temporal (OT) junction in reading has been established, yet there is current controversy over the region's specificity for reading and the nature of its role in the reading process. Recent neuroimaging findings suggest that the region is sensitive to orthographic familiarity [Kronbichler, M., Bergmann, J., Hutzler, F., Staffen, W., Mair, A., Ladurner, G., Wimmer, H. 2007. Taxi vs. Taksi: on orthographic word recognition in the left ventral occipito-temporal cortex. Journal of Cognitive Neuroscience 19, 1-11], and the present study tested that hypothesis. Using fMRI, the OT region and other regions in the reading network were localized in 28 adult, right-handed participants. The BOLD signal in these regions was measured during a phonological judgment task (i.e., "Does it sound like a word?"). Stimuli included words, pseudohomophones (phonologically familiar yet orthographically unfamiliar), and pseudowords (phonologically and orthographically unfamiliar) that were matched on lexical properties including sublexical orthography. Relative to baseline, BOLD signal in the OT region was greater for pseudohomophones than for words, suggesting that the region is sensitive to orthographic familiarity at the whole-word level. Further contrasts of orthographic frequency within the word condition revealed increased BOLD signal for low- than high-frequency words. Specialization in the OT region for recognition of frequent letter strings may support the development of reading expertise. Additionally, BOLD signal in the OT region correlates positively with reading efficiency, supporting the idea that this region is a skill zone for reading printed words. BOLD signal in the IFG and STG correlates negatively with reading efficiency, indicating that processing effort in these classic phonological regions is inversely related to reading efficiency.     

Asymmetric modulation of human visual cortex activity during 10 degrees lateral gaze (fMRI study)

We used BOLD fMRI to study the differential effects of the direction of gaze on the visual and the ocular motor systems. Fixation of a target straight ahead was compared to fixation of a target 10 degrees to the right and 10 degrees to the left from gaze straight ahead, and to eyes open in complete darkness in thirteen healthy volunteers. While retinotopic coordinates remained the same in all fixation conditions, the fixation target shifted with respect to a head-centered frame of reference. During lateral fixation, deactivations in higher-order visual areas (one ventral cluster in the lingual and fusiform gyri and one dorsal cluster in the postero-superior cuneus) and, as a trend, activations in early visual cortical areas were found predominantly in the hemisphere contralateral to the fixation target. We propose that visual processing is performed predominantly in the hemisphere contralateral to gaze direction, even during small gaze shifts into one visual hemifield. The excitability of visual neurons may be modulated depending on eye position to construct a head-centered frame of reference from a retinotopic input, thus allowing perceptual stability of space during eye movements. A further finding was that BOLD signal increases in fronto-parietal ocular motor and attentional structures were more pronounced during lateral than central fixation.     

Frontostriatal system in planning complexity: a parametric functional magnetic resonance version of Tower of London task

In the present study, we sought to investigate which brain structures are recruited in planning tasks of increasing complexity. For this purpose, a parametric self-paced pseudo-randomized event-related functional MRI version of the Tower of London task was designed. We tested 22 healthy subjects, enabling assessment of imaging results at a second (random effects) level of analysis. Compared with baseline, planning activity was correlated with increased blood oxygenation level-dependent (BOLD) signal in the dorsolateral prefrontal cortex, striatum, premotor cortex, supplementary motor area, and visuospatial system (precuneus and inferior parietal cortex). Task load was associated with increased activity in these same regions. In addition, increasing task complexity was correlated with activity in the left anterior prefrontal cortex, a region supposed to be specifically involved in third-order higher cognitive functioning.     

fMRI BOLD response to increasing task difficulty during successful paired associates learning

We used functional magnetic resonance imaging (fMRI) to assess cortical activations associated with increasing task difficulty (TD) in a visuospatial paired associates learning task. Encoding and retrieval were examined when 100% successful retrieval of three, four, or six object-location pairs had been attained (thus ensuring that performance was matched across subjects). As memory load increased, in general, the number of attempts taken to achieve 100% successful retrieval increased, while the number of trials correctly completed on the first attempt decreased. By modelling parametric variations in working memory load with BOLD signal changes we were able to identify brain regions displaying linear and nonlinear responses to increasing load. During encoding, load-independent activations were found in occipitoparietal cortices (excluding the precuneus for which linear load dependency was demonstrated), anterior cingulate, and cerebellum, while linear load-dependent activations in these same regions were found during retrieval. Nonlinear load-dependent responses, as identified by categorical contrasts between levels of load, were found in the right DLPFC and left inferior frontal gyrus. The cortical response to increasing cognitive demands or TD appears to involve the same, rather than an additional, network of brain regions "working harder."     

A comparison of neural circuits underlying auditory and visual object categorization

Knowledge about environmental objects derives from representations of multiple object features both within and across sensory modalities. While our understanding of the neural basis for visual object representation in the human and nonhuman primate brain is well advanced, a similar understanding of auditory objects is in its infancy. We used a name verification task and functional magnetic resonance imaging (fMRI) to characterize the neural circuits that are activated as human subjects match visually presented words with either simultaneously presented pictures or environmental sounds. The difficulty of the matching judgment was manipulated by varying the level of semantic detail at which the words and objects were compared. We found that blood oxygen level dependent (BOLD) signal was modulated in ventral and dorsal regions of the inferior frontal gyrus of both hemispheres during auditory and visual object categorization, potentially implicating these areas as sites for integrating polymodal object representations with concepts in semantic memory. As expected, BOLD signal increases in the fusiform gyrus varied with the semantic level of object categorization, though this effect was weak and restricted to the left hemisphere in the case of auditory objects.     

The Mental Number Line and the Human Angular Gyrus

To investigate the hemispheric organization of a language-independent spatial representation of number magnitude in the human brain we applied focal repetitive transcranial magnetic stimulation (rTMS) to the right or left angular gyrus while subjects performed a number comparison task with numbers between 31 and 99. Repetitive TMS over the angular gyrus disrupted performance of a visuospatial search task, and rTMS at the same site disrupted organization of the putative "number line." In some cases the pattern of disruption caused by angular gyrus rTMS suggested that this area normally mediates a spatial representation of number. The effect of angular gyrus rTMS on the number line task was specific. rTMS had no disruptive effect when delivered over another parietal region, the supramarginal gyrus, in either the left or the right hemisphere.     

Remembering forward: neural correlates of memory and prediction in human motor adaptation

We used functional MR imaging (FMRI), a robotic manipulandum and systems identification techniques to examine neural correlates of predictive compensation for spring-like loads during goal-directed wrist movements in neurologically-intact humans. Although load changed unpredictably from one trial to the next, subjects nevertheless used sensorimotor memories from recent movements to predict and compensate upcoming loads. Prediction enabled subjects to adapt performance so that the task was accomplished with minimum effort. Population analyses of functional images revealed a distributed, bilateral network of cortical and subcortical activity supporting predictive load compensation during visual target capture. Cortical regions - including prefrontal, parietal and hippocampal cortices - exhibited trial-by-trial fluctuations in BOLD signal consistent with the storage and recall of sensorimotor memories or “states” important for spatial working memory. Bilateral activations in associative regions of the striatum demonstrated temporal correlation with the magnitude of kinematic performance error (a signal that could drive reward-optimizing reinforcement learning and the prospective scaling of previously learned motor programs). BOLD signal correlations with load prediction were observed in the cerebellar cortex and red nuclei (consistent with the idea that these structures generate adaptive fusimotor signals facilitating cancelation of expected proprioceptive feedback, as required for conditional feedback adjustments to ongoing motor commands and feedback error learning). Analysis of single subject images revealed that predictive activity was at least as likely to be observed in more than one of these neural systems as in just one. We conclude therefore that motor adaptation is mediated by predictive compensations supported by multiple, distributed, cortical and subcortical structures.     

The role of the angular gyrus in the modulation of visuospatial attention by the mental number line

We tend to mentally organize numbers along a left-to-right oriented horizontal mental number line, with the smaller numbers occupying the more leftward positions. This mental number line has been shown to exert an influence on the visuospatial allocation of attention, with presentation of numbers from the low and high ends of the mental number line inducing covert shifts of spatial attention to the left and right side of visual space, respectively. However, the neural basis of this modulation is not known. Here we used transcranial magnetic stimulation (TMS) to study the role of the angular gyrus in shifts in visuospatial attention induced by the mental number line. We used a priming paradigm with a line bisection task to assess the bias in spatial allocation of visual attention induced by exposure to either small (16-24) or large (76-84) ends of the mental number line. In the Small Number Prime condition, when attention is presumably biased to the left side of visual space, TMS applied over the right angular gyrus during the delay between the prime and the target line abolished the effect of number priming. In contrast, application of TMS over the left angular gyrus had no significant effect. In the Large Number Prime condition (which shifted attention to the right side of visual space) both left and right TMS over the angular gyrus modulated the effect of number priming. This pattern of results reveals the involvement of the angular gyrus in the interaction between the mental number line and visual spatial attention.     

Exploring the visual world: the neural substrate of spatial orienting

Inspecting the visual environment, humans typically direct their attention across space by means of voluntary saccadic eye movements. Neuroimaging studies in healthy subjects have identified the superior parietal cortex and intraparietal sulcus as important structures involved in visual search. However, in apparent contrast, spatial disturbance of free exploration typically is observed after damage of brain structures located far more ventrally. Lesion studies in such patients disclosed the inferior parietal lobule (IPL) and temporo-parietal junction (TPJ), the superior temporal gyrus (STG) and insula, as well as the inferior frontal gyrus (IFG) of the right hemisphere. Here we used functional magnetic resonance imaging to investigate the involvement of these areas in active visual exploration in the intact brain. We conducted a region of interest analysis comparing free visual exploration of a dense stimulus array with the execution of stepwise horizontal and vertical saccades. The comparison of BOLD responses revealed significant signal increases during exploration in TPJ, STG, and IFG. This result calls for a reappraisal of the previous thinking on the function of these areas in visual search processes. In agreement with lesion studies, the data suggest that these areas are part of the network involved in human spatial orienting and exploration. The IPL dorsally of TPJ seem to be of minor importance for free visual exploration as these areas appear to be equally involved in the execution of spatially predetermined saccades.     

fMRI signal decreases in ipsilateral primary motor cortex during unilateral hand movements are related to duration and side of movement

Interactions between the primary motor cortices of each hemisphere during unilateral hand movements appear to be inhibitory, although there is evidence that the strengths of these interactions are asymmetrical. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the effects of motor task duration and hand used on unilateral movement-related BOLD signal increases and decreases in the hand region of primary motor cortex (M1) of each hemisphere in six right-handed volunteers. Significant task-related BOLD signal decreases were observed in ipsilateral M1 during single and brief bursts of unilateral movements for both hands. However, these negative-to-baseline responses were found to intensify with increasing movement duration in parallel with greater task-related increases in contralateral M1. Movement-related BOLD signal decreases in ipsilateral M1 were also stronger for the right, dominant hand than for the left hand in our right-handed subjects. These findings would be consistent with the existence of interhemispheric interactions between M1 of each hemisphere, whereby increased neuronal activation in M1 of one hemisphere induces reduced neuronal activity in M1 of the opposite hemisphere. The observation of a hemispheric asymmetry in inhibition between M1 of each hemisphere agrees well with previous neuroimaging and electrophysiological data. These findings are discussed in the context of current understanding of the physiological origins of negative-to-baseline BOLD responses.     

The effect of gender on planning: An fMRI study using the Tower of London task

Since the introduction of brain mapping, evidences of functional gender differences have been corroborating previous behavioral and neuropsychological results showing a sex-specific brain organization. We investigated gender differences in brain activation during the performance of the Tower of London (TOL) task which is a standardized test to assess executive functions. Eighteen healthy subjects (9 females and 9 males) underwent fMRI scanning while solving a series of TOL problems with different levels of difficulty. Data were analyzed by modeling both genders and difficulty task load. Task-elicited brain activations comprised a bilateral fronto-parietal network, common to both genders; within this network, females activated more than males in dorsolateral prefrontal cortex (DLPFC) and right parietal cortex, whereas males showed higher activity in precuneus. A prominent parietal activity was found at low level of difficulty while, with heavier task demand, several frontal regions and subcortical structures were recruited. Our results suggest peculiar gender strategies, with males relying more on visuospatial abilities and females on executive processing.     

Trial-by-trial coupling between EEG and BOLD identifies networks related to alpha and theta EEG power increases during working memory maintenance

PET and fMRI experiments have previously shown that several brain regions in the frontal and parietal lobe are involved in working memory maintenance. MEG and EEG experiments have shown parametric increases with load for oscillatory activity in posterior alpha and frontal theta power. In the current study we investigated whether the areas found with fMRI can be associated with these alpha and theta effects by measuring simultaneous EEG and fMRI during a modified Sternberg task This allowed us to correlate EEG at the single trial level with the fMRI BOLD signal by forming a regressor based on single trial alpha and theta power estimates. We observed a right posterior, parametric alpha power increase, which was functionally related to decreases in BOLD in the primary visual cortex and in the posterior part of the right middle temporal gyrus. We relate this finding to the inhibition of neuronal activity that may interfere with WM maintenance. An observed parametric increase in frontal theta power was correlated to a decrease in BOLD in regions that together form the default mode network. We did not observe correlations between oscillatory EEG phenomena and BOLD in the traditional WM areas. In conclusion, the study shows that simultaneous EEG-fMRI recordings can be successfully used to identify the emergence of functional networks in the brain during the execution of a cognitive task.     

Anatomy and time course of discrimination and categorization processes in vision: an fMRI study

Studies investigating the cerebral areas involved in visual processes generally oppose either different tasks or different stimulus types. This work addresses, by fMRI, the interaction between the type of task (discrimination vs. categorization) and the type of stimulus (Latin letters, well-known geometrical figures, and Korean letters). Behavioral data revealed that the two tasks did not differ in term of percentage of errors or correct responses, but a delay of 185 ms was observed for the categorization task in comparison with the discrimination task. All conditions activated a common neural network that includes both striate and extrastriate areas, especially the fusiform gyri, the precunei, the insulae, and the dorsolateral frontal cortex. In addition, interaction analysis revealed that the right insula was sensitive to both tasks and stimuli, and that stimulus type induced several significant signal variations for the categorization task in right frontal cortex, the right middle occipital gyrus, the right cuneus, and the left and right fusiform gyri, whereas for the discrimination task, significant signal variations were observed in the right occipito-parietal junction only. Finally, analyzing the latency of the BOLD signal also revealed a differential neural dynamics according to tasks but not to stimulus type. These temporal differences suggest a parallel hemisphere processing in the discrimination task vs. a cooperative interhemisphere processing in the categorization task that may reflect the observed differences in reaction time.     

Combination of event-related fMRI and diffusion tensor imaging in an infant with perinatal stroke

Focal ischemic brain injury, or stroke, is an important cause of later handicap in children. Early assessment of structure-function relationships after such injury will provide insight into clinico-anatomic correlation and potentially guide early intervention strategies. We used combined functional MRI (fMRI) with diffusion tensor imaging (DTI) in a 3-month-old infant to explore the structure-function relationship after unilateral perinatal stroke that involved the visual pathways. With visual stimuli, fMRI showed a negative BOLD activation in the visual cortex of the intact right hemisphere, principally in the anterior part, and no activation in the injured hemisphere. The functional activation in the intact hemisphere correlated clearly with the fiber tract of the optic radiation visualized with DTI. DTI confirmed the absence of the optic radiation in the damaged left hemisphere. In addition, event-related fMRI (ER-fMRI) experiments were performed to define the characteristics of the BOLD response. The shape is that of an inverted gamma function (similar to a negative mirror image of the known positive adult BOLD response). The maximum decrease was reached at 5-7 s with signal changes of -1.7 +/- 0.4%.Thus, this report describes for the first time the combined use of DTI and event-related fMRI in an infant and provides insight into the localization of the fMRI visual response in the young infant and the characteristics of the BOLD response.     

Visuospatial working memory and changes of the point of view in 3D space

We used functional magnetic resonance imaging to explore the brain mechanisms of changing point of view (PoV) in a visuospatial memory task in 3D space. Eye movements were monitored and BOLD signal changes were measured while subjects were presented with 3D images of a virtual environment. Subjects were required to encode the position of a lamp in the environment and, after changing the PoV (angular difference varied from 0 degrees to 180 degrees in 45 degrees steps), to decide whether the lamp position had been changed too or not. Performance data and a scan-path analysis based on eye movement support the use of landmarks in the environment for coding lamp position and increasing spatial updating costs with increasing changes of PoV indicating allocentric coding strategies during all conditions (0 degrees - to 180 degrees -condition). Subtraction analysis using SPM revealed that a parieto-temporo-frontal network including left medial temporal areas was activated during this 3D visuospatial task, independent of angular difference. The activity of the left parahippocampal area and the left lingual gyrus (but not the hippocampus) correlated with increasing changes of the PoV between encoding and retrieval, emphasizing their specific role in spatial scene memory and allocentric coding. The results suggest that these areas are involved in a continuous matching process between internal representations of the environment and the external status quo. In addition, hippocampal activation correlated with performance was found indicating successful recall of spatial information. Finally, in a prefrontal area comprising, the so-called "deep" frontal eye field, activation was correlated with the amount of saccadic eye movements confirming its role in oculomotor processes.     

Alcohol-induced suppression of BOLD activity during goal-directed visuomotor performance

The neurophysiological influence of alcohol produces deficits of many cognitive functions, including executive and motor control processes. This study examined the acute effects of alcohol in the context of goal-directed visuomotor performance during functional magnetic resonance imaging (fMRI). Subjects consumed alcohol-laced gelatin during one scan session and non-alcoholic placebo gelatin in another. During each session, subjects performed a visuomotor target capture where they received continuous or terminal positional feedback information. Blood-oxygen level-dependent (BOLD) activity in the cerebellum was suppressed in the presence of alcohol, consistent with the known ethanol sensitivity of the cerebellum. A fronto-parietal network was identified as most affected by alcohol consumption, with differential patterns of BOLD contingent on visual feedback. Results indicate that alcohol selectively suppresses cognitive activity in frontal and posterior parietal brain regions that, in conjunction with cerebellar nuclei, are believed to contribute to the formation of internal cognitive models of motor representation and action.     

Separating neural and vascular effects of caffeine using simultaneous EEG-FMRI: differential effects of caffeine on cognitive and sensorimotor brain responses

The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A(1) and A(2A) adenosine receptors resulting in increased neuronal activity but also vasoconstriction in the brain. Caffeine, therefore, can modify BOLD FMRI signal responses through both its neural and its vascular effects depending on receptor distributions in different brain regions. In this study we aim to distinguish neural and vascular influences of a single dose of caffeine in measurements of task-related brain activity using simultaneous EEG-FMRI. We chose to compare low-level visual and motor (paced finger tapping) tasks with a cognitive (auditory oddball) task, with the expectation that caffeine would differentially affect brain responses in relation to these tasks. To avoid the influence of chronic caffeine intake, we examined the effect of 250 mg of oral caffeine on 14 non and infrequent caffeine consumers in a double-blind placebo-controlled cross-over study. Our results show that the task-related BOLD signal change in visual and primary motor cortex was significantly reduced by caffeine, while the amplitude and latency of visual evoked potentials over occipital cortex remained unaltered. However, during the auditory oddball task (target versus non-target stimuli) caffeine significantly increased the BOLD signal in frontal cortex. Correspondingly, there was also a significant effect of caffeine in reducing the target evoked response potential (P300) latency in the oddball task and this was associated with a positive potential over frontal cortex. Behavioural data showed that caffeine also improved performance in the oddball task with a significantly reduced number of missed responses. Our results are consistent with earlier studies demonstrating altered flow-metabolism coupling after caffeine administration in the context of our observation of a generalised caffeine-induced reduction in cerebral blood flow demonstrated by arterial spin labelling (19% reduction over grey matter). We were able to identify vascular effects and hence altered neurovascular coupling through the alteration of low-level task FMRI responses in the face of a preserved visual evoked potential. However, our data also suggest a cognitive effect of caffeine through its positive effect on the frontal BOLD signal consistent with the shortening of oddball EEG response latency. The combined use of EEG-FMRI is a promising methodology for investigating alterations in brain function in drug and disease studies where neurovascular coupling may be altered on a regional basis.     

Regional variability of cerebral blood oxygenation response to hypercapnia

In functional magnetic resonance imaging studies changes in blood oxygenation level-dependent (BOLD) signal intensities during task activation are related to multiple physiological parameters such as cerebral blood flow, volume, and oxidative metabolism, as well as to the regional microvascular anatomy. Consequently, the magnitude of activation-induced BOLD signal changes may vary regionally and between subjects. The aim of this study was to use a uniform global stimulus such as hypercapnia to quantitatively investigate the regional BOLD response in the human brain. In 10 healthy volunteers, T2*-weighted gradient echo images were acquired for a total dynamic scanning time of 9 min during alternating periods of breath holding for 30 s after expiration and self-paced normal breathing for 60 s. Hypercapnia-induced BOLD signal changes in the sensorimotor cortex, frontal cortex, basal ganglia, visual cortex, and cerebellum were significantly different (P < 0.001) and varied from 1.8 to 5.1%. The highest BOLD signal changes were found in the cerebellum and visual cortex, whereas the lowest BOLD signal increase was observed in the frontal cortex. These results demonstrate a regional dependence of the BOLD signal changes during breath hold-induced hypercapnia, indirectly supporting the notion of regional different sensitivities of BOLD responses to task activation.     

Simulating transcranial magnetic stimulation during PET with a large-scale neural network model of the prefrontal cortex and the visual system.

Transcranial magnetic stimulation (TMS) exerts both excitatory and inhibitory effects on the stimulated neural tissue, although little is known about the neurobiological mechanisms by which it influences neuronal function. TMS has been used in conjunction with PET to examine interregional connectivity of human cerebral cortex. To help understand how TMS affects neuronal function, and how these effects are manifested during functional brain imaging, we simulated the effects of TMS on a large-scale neurobiologically realistic computational model consisting of multiple, interconnected regions that performs a visual delayed-match-to-sample task. The simulated electrical activities in each region of the model are similar to those found in single-cell monkey data, and the simulated integrated summed synaptic activities match regional cerebral blood flow (rCBF) data obtained in human PET studies. In the present simulations, the excitatory and inhibitory effects of TMS on both locally stimulated and distal sites were studied using simulated behavioral measures and simulated PET rCBF results. The application of TMS to either excitatory or inhibitory units of the model, or both, resulted in an increased number of errors in the task performed by the model. In experimental studies, both increases and decreases in rCBF following TMS have been observed. In the model, increasing TMS intensity caused an increase in rCBF when TMS exerted a predominantly excitatory effect, whereas decreased rCBF following TMS occurred if TMS exerted a predominantly inhibitory effect. We also found that regions both directly and indirectly connected to the stimulating site were affected by TMS.