Distinct Cortical Regions Research Articles

Resting-State Oscillatory Brain Dynamics in Alzheimer Disease

Altered oscillatory brain activity in Alzheimer disease (AD) may reflect underlying neuropathological changes, and its characterization might lead to new diagnostic possibilities. The present study using quantitative magnetoencephalography was set up to examine power spectrum changes in AD patients, and their diagnostic strength. Whole-head 151-channel magnetoencephalography was recorded during an eyes-closed resting state. Magnetoencephalography channels were grouped in 10 cortical regions, and both global and regional relative power was analyzed for the commonly used frequency bands. Eighteen AD patients [mean age 72.1 years +/- 5.6 (SD); 7 women; mean Mini Mental State Examination score 19.2, range: 13-25] and 18 healthy controls [mean age 69.1 +/- 6.8 (SD), 11 women; mean Mini Mental State Examination score 29, range: 27-30] were recruited, controls being mainly spouses of patients. Relative power analysis showed significant differences in most frequency bands, particularly in the temporo-parietal regions, with some relation to Mini Mental State Examination scores. Greatest diagnostic accuracy was found in the beta band, especially in the right occipital area (sensitivity 94%, specificity 78%). Quantitative relative power analysis of magnetoencephalography recordings is able to show widespread abnormalities in oscillatory brain dynamics in AD patients. By analyzing distinct cortical regions, this study provides a more detailed topographical view of abnormal brain activity in AD.

Connectivity Between Posterior Parietal Cortex and Ipsilateral Motor Cortex Is Altered in Schizophrenia

Recent advances have highlighted the hypothesis of schizophrenia as a disorder causing defective connectivity among distinct cortical regions. Neurophysiological evidence supporting this hypothesis, however, is still lacking. In the present study, we used a novel twin-coil transcranial magnetic stimulation (tcTMS) approach to investigate ipsilateral parieto-motor connectivity in 20 schizophrenic patients (14 medicated, 6 unmedicated) and in 15 healthy age-matched volunteers. In healthy subjects, a conditioning TMS pulse applied over the ipsilateral posterior parietal cortex (PPC) at 90% of resting motor threshold (RMT) intensity was able to increase the excitability of the hand area of the right primary motor cortex, with peaks at interstimulus intervals (ISIs) of 4 and 15 msec. This paradigm of stimulation failed to reveal any facilitatory parieto-motor interaction in medicated and unmedicated schizophrenic patients. The between-group difference in paired-pulse facilitation was not ISI-specific. In following analyses, we found that the effects across ISIs induced by PPC conditioning at 90% RMT correlated with the Global Assessment Functioning score and with the negative subscale of the Positive and Negative Syndrome Scale, showing that patients with a better global functioning and lower negative symptoms had less impaired connectivity. Moreover the same parameter correlated with illness duration. Parieto-motor connectivity is impaired in schizophrenia. Cortico-cortical disconnection might be a core feature of schizophrenia.

P1-388: Resting-state oscillatory brain dynamics in Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia, nevertheless it lacks a definitive antemortem diagnostic test. Altered resting-state oscillatory brain activity may reflect underlying neuropathological changes, and its characterization may lead to new diagnostic possibilities. Due to its superior temporal and spatial resolution compared to EEG, magnetoencephalography (MEG) is a promising technique for this purpose. The present study using MEG and spectral analysis was set up to study differences in relative power of oscillatory brain activity in ten distinct cortical regions. Whole-head 151-channel MEG was recorded in 18 AD patients (mean age 72.1 years, SD 5.6; 7 females; mean MMSE 19.2, range: 13–25) and 18 healthy controls (mean age 69.1, SD 6.8, 11 females; mean MMSE 29, range: 27–30) during a no-task eyes-closed resting state. MEG channels were grouped in ten distinct cerebral regions (central, frontal, occipital, parietal and temporal; both left and right), and relative power was calculated using the Fast Fourier Transformation. The analysis was done both globally and for the specific regions separately, for the delta (0.5–4 Hz), theta (4–8 Hz), alpha1 (8–10 Hz), alpha2 (10–13 Hz), beta (13–30 Hz), and the gamma (30–50 Hz) frequency band. Relative power analysis showed a widespread slowing of oscillatory brain activity, with significant differences in the delta, alpha1, alpha2 and beta frequency bands, particularly in the temporo-parietal regions. Greatest diagnostic accuracy was found in the beta band, especially in the right occipital area (sensitivity 94%, specificity 78%). Correlations of relative power and MMSE scores were generally weak, but with a positive trend in the alfa1 band (R=0.53). Resting-state oscillatory brain activity is different in Alzheimer's disease. Our findings confirm the well-known slowing of brain activity, and show that widespread regional differences between AD and healthy controls can be found using MEG and standard spectral analysis techniques. By analyzing specific cortical regions, this study gives a more detailed topographical view of abnormal oscillatory activity in AD, which may eventually contribute to a more definitive diagnosis in AD.

Key cortical subregions involved in basic visuo-spatial tasks: A systematic TMS mapping study of bilateral human parietal cortex

Several TMS studies have suggested that a multitude of distinct cortical regions contribute in a time- and task-dependent manner to the processing of space. We used a basic visual detection/localization task and apply TMS to systematically map, in an anatomically “blind” manner, the right and left parietal subregions likely to generate significant visuo-spatial biases.

The effects of priming on frontal-temporal communication

Repeated exposure to a stimulus facilitates its processing. This is reflected in faster and more accurate identification, reduced perceptual identification thresholds, and more efficient classifications for repeated compared with novel items. Here, we test a hypothesis that this experience-based behavioral facilitation is a result of enhanced communication between distinct cortical regions, which reduces local processing demands. A magnetoencephalographic investigation revealed that repeated object classification led to decreased neural responses in the prefrontal cortex and temporal cortex. Critically, this decrease in absolute activity was accompanied by greater neural synchrony (a measure of functional connectivity) between these regions with repetition. Additionally, the onset of the enhanced interregional synchrony predicted the degree of behavioral facilitation. These findings suggest that object repetition results in enhanced interactions between brain regions, which facilitates performance and reduces processing demands on the regions involved.

Prefrontal Cortical Involvement in Young Infants' Analysis of Novelty

Our knowledge of infant perception and cognition is primarily based on habituation and dishabituation, but the underlying neural mechanisms for these processes per se remain unclear. It has been argued that habituation is related to building internal representations of repeated stimuli in the central nervous system, whereas dishabituation is related to an increased attention to novel items and events. This leads to a hypothesis that a distributed network including the sensory, association and prefrontal cortical regions of young infants is involved in those processes, in contrast with the classical developmental view that onset of the functioning of the prefrontal cortex is delayed. Here we examined the time evolution of spatio-temporal hemodynamic responses related to the auditory habituation and dishabituation in the temporal and prefrontal regions of 3-month-old infants by using multichannel near-infrared spectroscopy. We found that the temporal regions remained activated by repetitive auditory stimuli; however, the prefrontal regions exhibited phasic activation in relation to novel stimuli. The dissociated activation pattern between the temporal and prefrontal regions suggests that distinct cortical regions play distinct functional roles in auditory habituation and dishabituation, and that the prefrontal cortex is involved in perceiving invariance or novelty of the immediate environment in early infancy.

Topographic Organization in and near Human Visual Area V4

The existence and location of a human counterpart of macaque visual area V4 are disputed. To resolve this issue, we used functional magnetic resonance imaging to obtain topographic maps from human subjects, using visual stimuli and tasks designed to maximize accuracy of topographic maps of the fovea and parafovea and to measure the effects of attention on topographic maps. We identified multiple topographic transitions, each clearly visible in > or = 75% of the maps, that we interpret as boundaries of distinct cortical regions. We call two of these regions dorsal V4 and ventral V4 (together comprising human area V4) because they share several defining characteristics with the macaque regions V4d and V4v (which together comprise macaque area V4). Ventral V4 is adjacent to V3v, and dorsal V4 is adjacent to parafoveal V3d. Ventral V4 and dorsal V4 meet in the foveal confluence shared by V1, V2, and V3. Ventral V4 and dorsal V4 represent complementary regions of the visual field, because ventral V4 represents the upper field and a subregion of the lower field, whereas dorsal V4 represents lower-field locations that are not represented by ventral V4. Finally, attentional modulation of spatial tuning is similar across dorsal and ventral V4, but attention has a smaller effect in V3d and V3v and a larger effect in a neighboring lateral occipital region.

Spatiotemporal dynamics of word processing in the human brain

We examined the spatiotemporal dynamics of word processing by recording the electrocorticogram (ECoG) from the lateral frontotemporal cortex of neurosurgical patients chronically implanted with subdural electrode grids. Subjects engaged in a target detection task where proper names served as infrequent targets embedded in a stream of task-irrelevant verbs and nonwords. Verbs described actions related to the hand (e.g, throw) or mouth (e.g., blow), while unintelligible nonwords were sounds which matched the verbs in duration, intensity, temporal modulation, and power spectrum. Complex oscillatory dynamics were observed in the delta, theta, alpha, beta, low, and high gamma (HG) bands in response to presentation of all stimulus types. HG activity (80–200 Hz) in the ECoG tracked the spatiotemporal dynamics of word processing and identified a network of cortical structures involved in early word processing. HG was used to determine the relative onset, peak, and offset times of local cortical activation during word processing. Listening to verbs compared to nonwords sequentially activates first the posterior superior temporal gyrus (post-STG), then the middle superior temporal gyrus (mid-STG), followed by the superior temporal sulcus (STS). We also observed strong phase-locking between pairs of electrodes in the theta band, with weaker phase-locking occurring in the delta, alpha, and beta frequency ranges. These results provide details on the first few hundred milliseconds of the spatiotemporal evolution of cortical activity during word processing and provide evidence consistent with the hypothesis that an oscillatory hierarchy coordinates the flow of information between distinct cortical regions during goal-directed behavior.

The specificity of interactions between the cortex and the thalamus.

The functioning of the adult mammalian cerebral cortex depends critically upon precise interconnections between specific thalamic nuclei and distinct cortical regions. Therefore, one central issue in understanding cortical development is determining the cellular and molecular strategies underlying the specification of thalamocortical projections. We address the role of axon-axon interactions and membrane-bound guidance molecules in the establishment of the development of layer-specific patterns of afferent and efferent cortical connections does not depend upon neuronal activity. We present evidence that activity conveyed by thalamic afferents is required for the elaboration of the columnar specificity of cortical circuits.

Evaluating the relationship of non-phase locked activities in the electroencephalogram during intermittent stimulation: a partial coherence-based approach

Partial coherence estimate between two signals removing the contribution of a periodic, deterministic one is proposed for measuring the coherence between two ongoing eletroencephalografic (EEG) activities collected at distinct cortical regions under sensory stimulation. The estimator expression was derived and shown to be independent of the stimulating signal. Simulations were used for obtaining the critical values for this coherence estimate. The technique was also evaluated throughout simulations and next applied to the EEG from 12 subjects under intermittent photic stimulation at 4 and 6 Hz. In both simulation and EEG data, major differences between partial and simple coherences occurred at the stimulation frequency and harmonics, except for those falling within the alpha band. These findings suggest that the technique is highly selective in removing the contribution of the periodic source. They also indicate high coherence values of the ongoing EEG within the alpha band.

Reliable simulations of the human proximal femur by high-order finite element analysis validated by experimental observations

Background: The mechanical response of patient-specific bone to various load conditions is of major clinical importance in orthopedics. Herein we enhance the methods presented in Yosibash et al. [2007. A CT-based high-order finite element analysis of the human proximal femur compared to in-vitro experiments. ASME Journal of Biomechanical Engineering 129(3), 297–309.] for the reliable simulations of the human proximal femur by high-order finite elements (FEs) and validate the simulations by experimental observations. Method of approach: A fresh-frozen human femur was scanned by quantitative computed tomography (QCT) and thereafter loaded (in vitro experiments) by a quasi-static force of up to 1250 N. QCT scans were manipulated to generate a high-order FE bone model with distinct cortical and trabecular regions having inhomogeneous isotropic elastic properties with Young's modulus represented by continuous spatial functions. Sensitivity analyses were performed to quantify parameters that mostly influence the mechanical response. FE results were compared to displacements and strains measured in the experiments. Results: Young moduli correlated to QCT Hounsfield Units by relations in Keyak and Falkinstein [2003. Comparison of in situ and in vitro CT scan-based finite element model predictions of proximal femoral fracture load. Medical Engineering and Physics 25, 781–787.] were found to provide predictions that match the experimental results closely. Excellent agreement was found for both the displacements and strains. The presented study demonstrates that reliable and validated high-order patient-specific FE simulations of human femurs based on QCT data are achievable for clinical computer-aided decision making.

Parallel thalamocortical pathways for echolocation and passive sound localization in a gleaning bat, Antrozous pallidus

We present evidence for parallel auditory thalamocortical pathways that serve two different behaviors. The pallid bat listens for prey-generated noise (5-35 kHz) to localize prey, while reserving echolocation [downward frequency-modulated (FM) sweeps, 60-30 kHz] for obstacle avoidance. Its auditory cortex contains a tonotopic map representing frequencies from 6 to 70 kHz. The high-frequency (BF > 30 kHz) representation is dominated by FM sweep-selective neurons, whereas most neurons tuned to lower frequencies prefer noise. Retrograde tracer injections into these physiologically distinct cortical regions revealed that the high-frequency region receives input from the suprageniculate (SG) nucleus, but not the ventral division of the medial geniculate body (MGBv), in all experiments (n = 9). In contrast, the low-frequency region receives tonotopically organized input from the MGBv in all experiments (n = 16). Labeling in the SG was observed in only two of these experiments. Both cortical regions also receive sparse inputs from medial (MGBm) and parts of the dorsal division (MGBd) outside the SG. These results show that the low- and high-frequency regions of a single tonotopic map receive dominant inputs from different thalamic divisions. Within the low-frequency region, most neurons are binaurally inhibited, and an orderly map of interaural intensity difference (IID) sensitivity is present. We show that the input to the IID map arises from topographically organized projections from the MGBv. As observed in other species, a frequency-dependent organization is observed in the lateromedial direction in the MGBv. These data demonstrate that MGBv-to-auditory cortex connections are organized with respect to both frequency and binaural selectivity.

Distinct and common cortical activations for multimodal semantic categories

If semantic representations are based on particular types of perceptual features, then category knowledge that arises from multimodal sensory experiences should rely on distinct and common sensory brain regions depending on the features involved. Using a similarity-based generation-and-comparison task, we found that semantic categories activated cortical areas associated with taste and smell, biological motion, and visual processing. Fruit names specifically activated medial orbitofrontal regions associated with taste and smell. Labels for body parts and clothing activated lateral temporal occipitoparietal areas associated with perceiving the human body. More generally, visually biased categories activated ventral temporal regions typically ascribed to visual object recognition, whereas functional categories activated lateral frontotemporal areas previously associated with the representation of usage properties. These results indicate that semantic categories that are distinguished by particular perceptual properties rely on distinct cortical regions, whereas semantic categories that rely on similar types of features depend on common brain areas.

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.

Cortical Representations of Temporal Structure in Sound

Pitch and spatial width are two sound attributes that can be coded by temporal acoustic structure. In this study, periodicity pitch was created by temporal iteration in a regular-interval noise, whereas spatial width was determined by the degree of interaural correlation. Previous results suggest that nonprimary auditory cortex, particularly lateral Heschl's gyrus (HG), plays an important role in the analysis of both acoustic properties. It has been argued that this role might reflect a common computational process. One proposed candidate is that of integrating the temporal pattern information across frequency channels. This paper reports the results of a systematic test for whether different classes of temporal structure do indeed engage a common neural architecture in the human auditory cortex by presenting both classes of sound stimuli to a single group of listeners. Activations related to the pitch and spatial width of the sound were partly co-localized in two distinct cortical regions: close to lateral HG and in planum temporale (PT). Lateral HG was more responsive to temporal pitch than to spatial width. This difference plus the variability across listeners for spatial width dispute the claim that the activity in lateral HG reflects a common neural computational step that encodes the temporal patterns associated with pitch and spatial width. Rather, the activity patterns are consistent with a role for lateral HG in perceptual analysis as opposed to temporal acoustic structure. In PT, the superadditive relationship between pitch and spatial width is also consistent with the concept that the auditory cortex plays an important role in integrating different classes of sound information to form auditory objects.

Regional differences in cortical bone mineral density in the weight-bearing long bone shaft—A pQCT study

This study used a multislice peripheral quantitative computed tomography (pQCT) to measure volumetric BMD (vBMD) and cortical thickness for investigating regional adaptation in lower tibial shaft in 72 healthy postmenopausal women aged 47–60. Tomographic slices were analysed on four distinct cortical regions: the anterior, posterior, medial and lateral cortical wall. One-way analysis of variance (ANOVA) test was used to compare the vBMD in the four regions. The results showed that the posterior cortex had the highest vBMD (1923 ± 135.3 mg/cm 3), significantly ( P < 0.001) higher than the anterior cortex (1805 ± 110.6 mg/cm 3), medial cortex (1863 ± 103.6 mg/cm 3) and lateral cortex (1815 ± 111.6 mg/cm 3); whereas there was no significant difference ( P > 0.05) between the medial and lateral cortices located near the neutral plane of bending. The anterior cortex had the greatest thickness (2.56 ± 0.47 mm), significantly ( P < 0.001) greater than that of the posterior cortex (2.11 ± 0.27 mm), medial cortex (2.20 ± 0.39 mm) and lateral cortex (2.03 ± 0.29 mm). The vBMD of the posterior cortex was a significant 6.5% higher than that of the anterior cortex ( P < 0.001); whereas the anterior cortical thickness was a significant 21.3% greater than that of the posterior cortex ( P < 0.001). There was no linear relationship found between cortical vBMD and cortical thickness measured at the four cortical regions ( r = 0.086, P > 0.05). In conclusion, the regional differences, with higher vBMD found in posterior cortex, might be a result of mechanical adaptation, which caused the posterior cortex to sustain higher compressive loading than the anterior tensile cortex during the landing phase in the gait cycles of individuals. Nevertheless, regional geometric adaptation in anterior cortical thickness might be adapted to accommodate for the reduced vBMD and to reduce the bending stress in this region.

Content-specificity of the neural correlates of recollection

It is widely assumed that episodic retrieval (recollection) involves reinstatement of cortical activity engaged during the processing of an episode when it was initially experienced. It follows from this assumption that the cortical correlates of recollection should differ with the content of what is recollected, and that retrieval of different content should be associated with activity in functionally distinct cortical regions. The present experiment investigated these predictions. Subjects ( N = 17) studied a mixed list of words and pictures and were then presented with a test list comprised of words only. Test items were studied words, the names of studied pictures, and unstudied (new) words. Functional magnetic resonance images were acquired while the subjects made Remember/Know/New judgments to these test words. Independent of study material, studied items endorsed as Remembered elicited greater activity than correctly classified unstudied items in several regions, including left frontal, left lateral parietal, and posterior cingulate cortex. In addition, Remembered items elicited greater activity in the right hippocampus and parahippocampal gyrus than items accorded Know judgments, replicating previous findings. Analysis of content-specific effects demonstrated a regional double-dissociation within left fusiform cortex; recollected words elicited greater activity than recollected pictures in lateral fusiform, whereas the reverse effect was evident in an anterior fusiform region. The lateral and anterior fusiform areas correspond closely to areas held to be functionally specialized for the processing of visual words and pictures, respectively. Thus, the current findings support the cortical reinstatement hypothesis of episodic retrieval.

On the role of general system theory for functional neuroimaging.

One of the most important goals of neuroscience is to establish precise structure-function relationships in the brain. Since the 19th century, a major scientific endeavour has been to associate structurally distinct cortical regions with specific cognitive functions. This was traditionally accomplished by correlating microstructurally defined areas with lesion sites found in patients with specific neuropsychological symptoms. Modern neuroimaging techniques with high spatial resolution have promised an alternative approach, enabling non-invasive measurements of regionally specific changes of brain activity that are correlated with certain components of a cognitive process. Reviewing classic approaches towards brain structure-function relationships that are based on correlational approaches, this article argues that these approaches are not sufficient to provide an understanding of the operational principles of a dynamic system such as the brain but must be complemented by models based on general system theory. These models reflect the connectional structure of the system under investigation and emphasize context-dependent couplings between the system elements in terms of effective connectivity. The usefulness of system models whose parameters are fitted to measured functional imaging data for testing hypotheses about structure-function relationships in the brain and their potential for clinical applications is demonstrated by several empirical examples.

Topography of cortico-striatal connections in man: anatomical evidence for parallel organization.

Tracing studies in non-human primates support the existence of several parallel neuronal circuits involving cerebral cortex, basal ganglia and thalamus. Distinct functional loops were proposed to underlie multiple aspects of normal and pathological behaviour in man. We present here the first anatomical evidence for separate corticostriatal systems in humans. Neural connections of the sensorimotor and prefrontal cortex to the striatum were studied in one human brain using the Nauta method for anterogradely degenerating axons. Axons originating from a lesion in the left sensorimotor cortex, including the face area, were found to terminate in the superolateral part of the ipsilateral putamen, forming a narrow band in its posterior part. Inside the band, the distribution of degenerating axons was inhomogeneous; high-density clusters of approximately 2.5 mm in diameter were separated by regions with less dense cortical projections. Axons originating from a small lesion in the fundus of the right superior frontal sulcus were found in the upper part of the ipsilateral caudate nucleus. The existence of discrete and anatomically segregated terminal patches originating from distinct cortical regions suggests parallel organization of cortico-striatal connections in man.

Blockade of the extracellular signal-regulated kinase pathway by U0126 attenuates neuronal damage following circulatory arrest

ObjectivesThe extracellular signal-regulated kinase pathway of the mitogen-activated protein kinase signal transduction cascade has been implicated in the neuronal and endothelial dysfunction witnessed following cerebral ischemia-reperfusion injury. Extracellular signal-regulated kinase is activated by mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2. We evaluated the ability of a mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2–specific inhibitor (U0126) to block extracellular signal-regulated kinase activation and mitigate ischemic neuronal damage in a model of deep hypothermic circulatory arrest. MethodsPiglets underwent normal flow cardiopulmonary bypass (control, n = 4), deep hypothermic circulatory arrest (n = 6), and deep hypothermic circulatory arrest with U0126 (n = 5) at 20°C for 60 minutes. The deep hypothermic circulatory arrest with U0126 group was given 200 μg/kg of U0126 45 minutes prior to initiation of bypass followed by 100 μg/kg at reperfusion. Following 24 hours of post–cardiopulmonary bypass recovery, brains were harvested. Eleven distinct cortical regions were evaluated for neuronal damage using hematoxylin and eosin staining. A section of ischemic cortex was further evaluated by immunohistochemistry with rabbit polyclonal antibody against phosphorylated extracellular signal-regulated kinase 1/2. ResultsThe deep hypothermic circulatory arrest and deep hypothermic circulatory arrest with U0126 groups displayed diffuse ischemic changes. However, the deep hypothermic circulatory arrest with U0126 group possessed significantly lower neuronal damage scores in the right frontal watershed zone of cerebral cortex, basal ganglia, and thalamus (P ≤ .05) and an overall trend toward neuroprotection versus the deep hypothermic circulatory arrest group. This neuroprotection was accompanied by nearly complete blockade of phosphorylated extracellular signal-regulated kinase in the cerebral vascular endothelium. ConclusionsIn this experimental model of deep hypothermic circulatory arrest, U0126 blocked extracellular signal-regulated kinase activation and provided a significant neuroprotective effect. These results support targeting of the extracellular signal-regulated kinase pathway for inhibition as a novel therapeutic approach to mitigate neuronal damage following deep hypothermic circulatory arrest.