Dissociating prefrontal and parietal cortex activation during arithmetic processing

Lesion and brain-imaging studies have implicated the prefrontal and parietal cortices in arithmetic processing, but do not exclude the possibility that these brain areas are also involved in nonarithmetic operations. In the present study, we used functional magnetic resonance imaging to explore which brain areas contribute uniquely to numeric computation. Task difficulty was manipulated in a factorial design by varying the number of operands and the rate of stimulus presentation. Both manipulations increased the number of operations to be performed in unit time. Manipulating the number of operands allowed us to investigate the specific effect of calculation, while manipulating the rate of presentation allowed us to increase task difficulty independent of calculation. We found quantitative changes in activation patterns in the prefrontal and parietal cortices as well as the recruitment of additional brain regions, including the caudate and midcerebellar cortex, with increasing task difficulty. More importantly, the main effect of arithmetic complexity was observed in the left and right angular gyrus, while the main effect of rate of stimulus presentation was observed in the left insular/orbitofrontal cortex. Our findings indicate a dissociation in prefrontal and parietal cortex function during arithmetic processing and further provide the first evidence for a specific role for the angular gyrus in arithmetic computation independent of other processing demands.     

Dynamic activation of the anterior cingulate cortex during anticipatory anxiety

Based on theoretical models, we investigated the dynamics of brain activation during anticipatory anxiety using functional magnetic resonance imaging and a combined parametric/correlational design. Subjects (16 females) anticipated the application of electrical shocks of varying intensity resulting in four different threat levels. The parametric analysis revealed an inverted U-function of activation in the ventral anterior cingulate cortex (ACC) depending on the level of threat. Furthermore, the correlation analysis showed that the association between anxiety and brain activation in the pregenual ACC was, as a tendency, positive during moderate threat but clearly negative during strong threat. Moreover, during strong threat, a positive correlation between anxiety and activation was observed in the dorsal ACC, somatosensory cortex, motor cortex, and hippocampus. These findings suggest threat dependent dynamics of brain activation in the ACC; with increased attentional avoidance during moderate threat and a switch to hypervigilant action readiness in the most anxious subjects during strong threat.     

Functional network in the prefrontal cortex during episodic memory retrieval

A recent consistent finding in neuroimaging studies of human memory is that the prefrontal cortex (PFC) is activated during episodic memory retrieval. To date, however, there has been no direct evidence to explain how activity in the right and left PFC and in the anterior and posterior PFC are functionally interconnected. The goal of the present study was to obtain such evidence by event-related functional magnetic resonance imaging (MRI) and the functional connectivity method. Subjects were first asked to try to remember a series of associate-word lists outside the MRI scanner in preparation for a later recognition test. In the MRI scanning phase, they were asked to make recognition judgments in regard to old words, semantically related lure words, and unrelated new words. The analysis of functional connectivity revealed that the posterior PFC in each hemisphere had strong functional interconnections with the contralateral posterior PFC, whereas the anterior PFC in each hemisphere had only weak functional interconnections with the contralateral anterior PFC. No strong functional interconnections were found between the anterior and posterior PFC in either hemisphere. These findings support the hypothesis of an associative contribution of the bilateral posterior PFC to episodic memory retrieval and a dissociative contribution of the bilateral anterior PFC.     

Perirhinal cortex activity during visual object discrimination: an event-related fMRI study

Previous fMRI studies have demonstrated preferential involvement of the perirhinal cortex and hippocampus in tasks of object and spatial memory, respectively. Here we investigated whether similar activity would also be present when object and spatial discrimination was assessed in the absence of explicit declarative memory demands. On each trial in the scanner, participants were presented simultaneously with two arrays of objects and were asked to indicate whether both arrays were identical, differed with respect to the identity of one object or differed with respect to the spatial arrangement of the objects. It was found that the detection of an object identity change was associated with significant right perirhinal cortex activity. We suggest that this perirhinal activity indicates a role of this structure in processes beyond declarative memory, for example, short-term visual working memory or higher order perception. Significantly greater hippocampal activity was not, however, observed during the spatial arrangement condition, perhaps due to the relatively low spatial processing demands of this task.     

Functional specialization for semantic and phonological processing in the left inferior prefrontal cortex.

Neuroimaging and neuropsychological studies have implicated left inferior prefrontal cortex (LIPC) in both semantic and phonological processing. In this study, functional magnetic resonance imaging was used to examine whether separate LIPC regions participate in each of these types of processing. Performance of a semantic decision task resulted in extensive LIPC activation compared to a perceptual control task. Phonological processing of words and pseudowords in a syllable-counting task resulted in activation of the dorsal aspect of the left inferior frontal gyrus near the inferior frontal sulcus (BA 44/45) compared to a perceptual control task, with greater activation for nonwords compared to words. In a direct comparison of semantic and phonological tasks, semantic processing preferentially activated the ventral aspect of the left inferior frontal gyrus (BA 47/45). A review of the literature demonstrated a similar distinction between left prefrontal regions involved in semantic processing and phonological/lexical processing. The results suggest that a distinct region in the left inferior frontal cortex is involved in semantic processing, whereas other regions may subserve phonological processes engaged during both semantic and phonological tasks.     

Early lateralization and orientation tuning for face, word, and object processing in the visual cortex

Event-related potential (ERP) studies of the human brain have shown that object categories can be reliably distinguished as early as 130-170 ms on the surface of occipito-temporal cortex, peaking at the level of the N170 component. Consistent with this finding, neuropsychological and neuroimaging studies suggest major functional distinctions within the human object recognition system, particularly in hemispheric advantage, between the processing of words (left), faces (right), and objects (bilateral). Given these observations, our aim was to (1) characterize the differential response properties of the N170 to pictures of faces, objects, and words across hemispheres; and (2) test whether an effect of inversion for highly familiar and monooriented nonface stimuli such as printed words can be observed at the level of the N170. Scalp EEG (53 channels) was recorded in 15 subjects performing an orientation decision task with pictures of faces, words, and cars presented upright or inverted. All three categories elicited at the same latency a robust N170 component associated with a positive counterpart at centro-frontal sites (vertex-positive potential, VPP). While there were minor amplitude differences at the level of the occipital medial P1 between linguistic and nonlinguistic categories, scalp topographies and source analyses indicated strong hemispheric and orientation effects starting at the level of the N170, which was right lateralized for faces, smaller and bilateral for cars, and as large for printed words in the left hemisphere as for faces. The entire N170/VPP complex was accounted for by two dipolar sources located in the lateral inferior occipital cortex/posterior fusiform gyrus. These two locations were roughly equivalent across conditions but differed in strength and lateralization. Inversion delayed the N170 (and VPP) response for all categories, with an increasing delay for cars, words, and faces, respectively, as suggested by source modeling analysis. Such results show that early processes in object recognition respond to category-specific visual information, and are associated with strong lateralization and orientation bias.     

Neurovascular coupling during nociceptive processing in the primary somatosensory cortex of the rat

Neuroimaging methods such as functional magnetic resonance imaging (fMRI) have been used extensively to investigate pain-related cerebral mechanisms. However, these methods rely on a tight coupling of neuronal activity to hemodynamic changes. Because pain may be associated with hemodynamic changes unrelated to local neuronal activity (eg, increased mean arterial pressure [MAP]), it is essential to determine whether the neurovascular coupling is maintained during nociceptive processing. In this study, local field potentials (LFP) and cortical blood flow (CBF) changes evoked by electrical stimulation of the left hind paw were recorded concomitantly in the right primary somatosensory cortex (SI) in 15 rats. LFP, CBF, and MAP changes were examined in response to stimulus intensities ranging from 3 to 30 mA. In addition, LFP, CBF, and MAP changes evoked by a 10-mA stimulation were examined during immersion of the tail in non-nociceptive or nociceptive hot water (counter-stimulation). SI neurovascular coupling was altered for stimuli of nociceptive intensities (P < 0.001). This alteration was intensity-dependent and was strongly associated with MAP changes (r = 0.98, P < 0.001). However, when the stimulus intensity was kept constant, SI neurovascular coupling was not significantly affected by nociceptive counter-stimulation (P = 0.4), which similarly affected the amplitude of shock-evoked LFP and CBF changes. It remains to be determined whether such neurovascular uncoupling occurs in humans, and whether it also affects other regions usually activated by painful stimuli. These results should be taken into account for accurate interpretation of fMRI studies that involve nociceptive stimuli associated with MAP changes.     

Pilot study investigating infant vagal reactivity and visual behavior during object perception.

OBJECTIVE: The authors examined whether changes in vagal tone were related to infant visual attention during auditory and visual events paired (synchronous) and not paired (asynchronous) in time. They predicted that infants would demonstrate greater visual attention to the synchronous slideshow and that vagal tone would decrease with visual attention. METHOD: Nineteen infants, 3.5 months old, watched computer-generated synchronous or asynchronous slideshows of auditory and visual stimuli. Visual behavior and vagal tone data were collected. Vagal tone reflects physiological responses during attention or exposure to mild stressors. Repeated-measures analysis of variance examined differences in vagal tone across conditions. RESULTS: Visual behavior did not differ between the synchronous and asynchronous slideshow conditions. Vagal tone was significantly lower during the asynchronous slideshow. CONCLUSION: Infants may discriminate synchronous from asynchronous stimuli without changing visual behavior. Implications related to play with toys or objects are discussed.     

Functional activation of the cerebral cortex related to sensorimotor adaptation of reactive and voluntary saccades

Potentially dangerous events in the environment evoke automatic ocular responses, called reactive saccades. Adaptation processes, which maintain saccade accuracy against various events (e.g. growth, aging, neuro-muscular lesions), are to date mostly relayed to cerebellar activity. Here we demonstrate that adaptation of reactive saccades also involves cerebral cortical areas. Moreover, we provide the first identification of the neural substrates of adaptation of voluntary saccades, representing the complement to reactive saccades for the active exploration of our environment. An fMRI approach was designed to isolate adaptation from saccade production: an adaptation condition in which the visual target stepped backward 50 ms after saccade termination was compared to a control condition where the same target backstep occurred 500 ms after saccade termination. Subjects were tested for reactive and voluntary saccades in separate sessions. Multi-voxel pattern analyses of fMRI data from previously-defined regions of interests (ROIs) significantly discriminated between adaptation and control conditions for several ROIs. Some of these areas were revealed for adaptation of both saccade categories (cerebellum, frontal cortex), whereas others were specifically related to reactive saccades (temporo-parietal junction, hMT+/V5) or to voluntary saccades (medial and posterior areas of intra-parietal sulcus). These findings critically extend our knowledge on brain motor plasticity by showing that saccadic adaptation relies on a hitherto unknown contribution of the cerebral cortex.     

Frontal lobe activation during object permanence: data from near-infrared spectroscopy

The ability to create and hold a mental schema of an object is one of the milestones in cognitive development. Developmental scientists have named the behavioral manifestation of this competence object permanence. Convergent evidence indicates that frontal lobe maturation plays a critical role in the display of object permanence, but methodological and ethical constrains have made it difficult to collect neurophysiological evidence from awake, behaving infants. Near-infrared spectroscopy provides a noninvasive assessment of changes in oxy- and deoxyhemoglobin and total hemoglobin concentration within a prescribed region. The evidence described in this report reveals that the emergence of object permanence is related to an increase in hemoglobin concentration in frontal cortex.     

Functional MRI shows activation of the medial preoptic area during sleep

Changes in the activity of the basal forebrain sleep regulating areas were studied noninvasively in conscious rats by employing functional magnetic resonance imaging (fMRI). Sleep-wakefulness (S-W) stages were identified with the help of electrophysiological recordings carried out simultaneously. An increase in the signal intensity was observed in the medial preoptic area (mPOA) during sleep indicating a heightened activity of neurons in this area. In some rats, there was a decrease in the activity of the fronto-parietal cortex. The sleep-induced increase in activity in the mPOA and decrease in the fronto-parietal cortex are in relation to their levels in the awake state. The findings helped to localize the critical area for the maintenance of slow wave sleep at the mPOA. These results further corroborate some of the previous suggestions based on neurotoxic lesion, chemical stimulation and electrophysiological recordings.     

Selective enhancement of functional connectivity in the left prefrontal cortex during sentence processing

We present the results of correlation analyses for identifying temporally correlated activations between multiple regions of interest. We focused on functional connectivity for two regions in the prefrontal cortex: the left inferior frontal gyrus (L. F3t/F3O) and the left precentral sulcus (L. PrCS). Temporal correlations of functional magnetic resonance imaging signals were separately examined during a sentence comprehension task and a lexical decision task, thereby averaging data throughout all voxels within a region of interest used as a reference region. We found that the reciprocal connectivity between L. F3t/F3O and L. PrCS was significantly enhanced during sentence processing, but not during lexico-semantic processing, which was confirmed under both auditory and visual conditions. Furthermore, significantly correlated regions were mostly concentrated in the left prefrontal cortex during the sentence task. These results demonstrate that the functional connectivity within the left prefrontal cortex is selectively enhanced for processing sentences, which may subserve the use of syntactic information for integrating lexico-semantic information.     

The role of frontopolar cortex in subgoal processing during working memory

Neuroimaging studies have implicated the anterior-most or frontopolar regions of prefrontal cortex (FP-PFC, e.g., Brodmann's Area 10) as playing a central role in higher cognitive functions such as planning, problem solving, reasoning, and episodic memory retrieval. The current functional magnetic resonance imaging (fMRI) study tested the hypothesis that FP-PFC subserves processes related to the monitoring and management of subgoals, while maintaining information in working memory (WM). Subjects were scanned while performing two variants of a simple delayed response WM task. In the control WM condition, subjects monitored for the presence of a specific concrete probe word (LIME) occurring following a specific abstract cue word (FATE). In the subgoal WM condition, subjects monitored for the presence of any concrete probe word immediately following any abstract cue word. Thus, the task required semantic classification of the probe word (the subgoal task), while the cue was simultaneously maintained in WM, so that both pieces of information could be integrated into a target determination. In a second control condition, subjects performed abstract/concrete semantic classification without WM demands. A region within right FP-PFC was identified which showed significant activation during the subgoal WM condition, but no activity in either of the two control conditions. However, this FP-PFC region was not modulated by direct manipulation of active maintenance demands. In contrast, left dorsolateral PFC was affected by active maintenance demands, but the effect did not interact with the presence of a subgoal task. Finally, left ventral PFC regions showed activation in response to semantic classification, but were not affected by WM demands. These results suggest a triple dissociation of function within PFC regions, and further indicate that FP-PFC is selectively engaged by the requirement to monitor and integrate subgoals during WM tasks.     

Zones of bimanual and unimanual preference within human primary sensorimotor cortex during object manipulation

We asked which brain areas are engaged in the coordination of our hands in dexterous object manipulations where they cooperate for achieving a common goal. Well-trained right-handers steered a cursor on a screen to hit successively displayed targets by applying isometric forces and torques to a rigid tool. In two bimanual conditions, the object was held freely in the air and the hands thus generated coupled opposing forces. Yet, depending on the mapping rule linking hand forces and cursor movements, all subjects selected either the left or the right hand as prime actor. In two unimanual conditions, the subjects performed the same task with either the left or the right hand operating on a fixed tool. Functional magnetic resonance imaging revealed common activation across all four conditions in a dorsal fronto-parietal network biased to the left hemisphere and in bilateral occipitotemporal cortex. Contrary to the notion that medial wall premotor areas are especially active in complex bimanual actions, their activation depended on acting hand (left, right) rather than on grip type (bimanual, unimanual). We observed effects of grip type only in the primary sensorimotor cortex (SMC). In particular, with either hand as prime actor, bimanual actions preferentially activated subregions of the SMC contralateral to the acting hand. A sizeable subregion with preference for unimanual activity was found only in the left SMC in our right-handed subjects. Collectively, these results indicate a hemispheric asymmetry for the SMC and that partially different neural populations support the control of bimanual versus unimanual object manipulations.     

Functional imaging of the intraparietal cortex during saccades to visual and memorized targets

The representation of perceived space and intended actions in the primate parietal cortex has been the subject of considerable debate. To address this issue, we used the quantitative 14C-deoxyglucose method to obtain maps of the activity pattern in the intraparietal cortex of rhesus monkeys executing saccades to visual and memorized targets. The principal effect induced by memory-guided saccades was found more caudally in the deepest part of the middle third of the lateral bank (within area LIPv) whereas that induced by visually guided saccades extended more rostrally and superficially in the anterior third of the bank (within area LIPd). The memory-saccade-related and the visual-saccade-related regions of activation overlapped only within area LIPv. Besides saccade execution, maximal activity in area LIPd required a visual stimulus. The region activated by visual fixation was located at the border of LIPv and LIPd, extending mainly within area LIPd, and occupying about one third of the neural space of the region activated for visual-saccades. We suggest that the lateral intraparietal cortex represents visual and motor space in segregated, albeit partially overlapping, regions.     

Occipito-parietal cortex activation during visuo-spatial imagery in early blind humans

Using positron emission tomography, regional cerebral blood flow was studied in five early blind and five control volunteers during visuo-spatial imagery. Subjects were instructed to generate a mental representation of verbally provided bidimensional patterns that were placed in a grid and to assess pattern symmetry in relation to a grid axis. This condition was contrasted with a verbal memory task. Cerebral activation in both groups was similar during the visuo-spatial imagery task. It involved the precuneus (BA 7), superior parietal lobule (BA 7), and occipital gyrus (BA 19). These results are in accordance with previous studies conducted in sighted subjects that indicated that the same occipito-parietal areas are involved in visual perception as well as in mental imagery dealing with spatial components. The dorsal pathway seems to be involved in visuo-spatial imagery in early blind subjects, indicating that this pathway undergoes development in the absence of vision.     

Gender differences in the activation of inferior frontal cortex during emotional speech perception

We investigated the brain regions that mediate the processing of emotional speech in men and women by presenting positive and negative words that were spoken with happy or angry prosody. Hence, emotional prosody and word valence were either congruous or incongruous. We assumed that an fRMI contrast between congruous and incongruous presentations would reveal the structures that mediate the interaction of emotional prosody and word valence. The left inferior frontal gyrus (IFG) was more strongly activated in incongruous as compared to congruous trials. This difference in IFG activity was significantly larger in women than in men. Moreover, the congruence effect was significant in women whereas it only appeared as a tendency in men. As the left IFG has been repeatedly implicated in semantic processing, these findings are taken as evidence that semantic processing in women is more susceptible to influences from emotional prosody than is semantic processing in men. Moreover, the present data suggest that the left IFG mediates increased semantic processing demands imposed by an incongruence between emotional prosody and word valence.     

NMDA-receptor activation and nitroxidative regulation of the glutamatergic pathway during nociceptive processing

The role of peroxynitrite (PN) as a mediator of nociceptive signaling is emerging. We recently reported that the development of central sensitization that follows the intraplantar injection of carrageenan in rats is associated with spinal PN synthesis. We now demonstrate that a significant pathway through which spinal PN modulates central sensitization is post-translational tyrosine nitration of key proteins involved in the glutamatergic pathway, namely glutamate transporter GLT-1 and glutamine synthetase (GS). We also reveal that spinal activation of the N-methyl-d-aspartate (NMDA) receptor provides a source of PN in this setting. Intraplantar injection of carrageenan led to the development of thermal hyperalgesia as well as nitration of GLT-1 and GS in dorsal horn tissues. Pretreatment with the PN decomposition catalyst FeTM-4-PyP⁵⁺ [Fe(III)5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin] or the NMDA receptor antagonist MK-801 blocked the development of hyperalgesia. Carrageenan-induced hyperalgesia was also associated with nitration and inactivation of spinal mitochondrial superoxide dismutase (MnSOD) known to provide a critical source of PN during central sensitization. Nitration of GLT-1 and GS contributes to central sensitization by enhancing glutamatergic neurotransmission. Our results support the critical role of nitroxidative stress in the development of hyperalgesia and suggest that post-translational nitration of enzymes and transporters linked to glutamatergic neurotransmission represent a novel mechanism of central sensitization.     

Global activation of primary motor cortex during voluntary movements in man

Unilateral voluntary movements are accompanied by robust activation of contralateral primary motor cortex (M1) in a somatotopic fashion. Occasionally, coactivation of M1 (M1-CoA) ipsilateral to the movement was described. In a study with brain tumor patients, we consistently observed additional somatotopic M1-CoAs and hypothesized that they might represent a basic feature of movement execution. To test this hypothesis, we used BOLD functional magnetic resonance imaging in healthy subjects and show that unilateral voluntary movements of the fingers or toes go along not only with contralateral M1 activation, but also with ipsilateral M1-CoA of the respective homotopic representation and bilateral M1-CoA of different heterotopic representations not directly involved in the executed movement. Moreover, bilateral M1-CoA of heterotopic representations was observed in tongue movements. All M1-CoAs respected the correct somatotopy; however, their Euclidean coordinates were shifted and resembled to those obtained for imagined movements rather than for actual movements. BOLD signal intensities and correlations to the applied hemodynamic reference function were lower in M1-CoAs as compared to the M1 activations driving the movement but did not differ between homo- and heterotopic M1-CoAs. Thus, we propose that specific unilateral voluntary movements are accompanied by a global activation of primary motor areas, reflecting an overall increase in neuronal activity and unraveling the fundamental principle of distributed processing in M1. Executive motor function may rely on a balance of inhibitory and excitatory neuronal activity, where actual movement would result from a shift towards excitation.     

Functional biomechanics of the thoracolumbar vertebral cortex

Studies were conducted on human cadaver thoracolumbar vertebrae, at the T₁₂−L₅ level, of five males and six females. Isolated vertebral bodies, free of posterior elements, were first scanned using dual photon absorptiometry and then underwent axial compressive loading. All of the vertebral bodies failed as a result of compressive fractures of the bone. Results indicated that the mechanical load-deflection response was non-linear and biphasic. The mean cross-sectional areas of the vertebral bodies progressively increased from L₁, to L₅. The maximum load carrying capacity was not dependent upon spinal level. The bone mineral content (BMC) obtained using dual photon absorptiometry in the lateral projected plane increased from L, to L5. Male vertebral bodies consistently had higher BMC than female specimens. The cortical shell contributed 12·44% (mean) of the total cross-sectional area in the male, 17·56% in the female; 8·85% of the BMC in the male and 1654% in the female. In contrast, it accounted for 43·8% (mean) of the total load in the male compared to 35·2% in the female specimens. Mean failure loads of decorticated vertebrae were significantly lower (p<0.001) when compared with that of the adjacent intact vertebral bodies. In one osteoporotic spine, the cortical shell accounted for 74% of the total strength. The anatomical placement of the thin shell which enables it to act as an encasing element to resist the collapse of the trabeculae under compression, and the difference in rigidity of the two structural components, and their differing sensitivity to metabolic influences, seem to explain this relatively high magnitude of load absorption in spite of its limited contribution to vertebral geometry.