The role of egocentric and allocentric abilities in Alzheimer's disease: A systematic review

A great effort has been made to identify crucial cognitive markers that can be used to characterize the cognitive profile of Alzheimer's disease (AD). Because topographical disorientation is one of the earliest clinical manifestation of AD, an increasing number of studies have investigated the spatial deficits in this clinical population. In this systematic review, we specifically focused on experimental studies investigating allocentric and egocentric deficits to understand which spatial cognitive processes are differentially impaired in the different stages of the disease. First, our results highlighted that spatial deficits appear in the earliest stages of the disease. Second, a need for a more ecological assessment of spatial functions will be presented. Third, our analysis suggested that a prevalence of allocentric impairment exists. Specifically, two selected studies underlined that a more specific impairment is found in the translation between the egocentric and allocentric representations. In this perspective, the implications for future research and neurorehabilitative interventions will be discussed.     

Separating neural correlates of allocentric and egocentric neglect: Distinct cortical sites and common white matter disconnections

Insights into the functional nature and neuroanatomy of spatial attention have come from research in neglect patients but to date many conflicting results have been reported. The novelty of the current study is that we used voxel-wise analyses based on information from segmented grey and white matter tissue combined with diffusion tensor imaging to decompose neural substrates of different neglect symptoms. Allocentric neglect was associated with damage to posterior cortical regions (posterior superior temporal sulcus, angular, middle temporal and middle occipital gyri). In contrast, egocentric neglect was associated with more anterior cortical damage (middle frontal, postcentral, supramarginal, and superior temporal gyri) and damage within subcortical structures. Damage to intraparietal sulcus (IPS) and the temporo-parietal junction (TPJ) was associated with both forms of neglect. Importantly, we showed that both disorders were associated with white matter lesions suggesting damage within long association and projection pathways such as the superior longitudinal, superior fronto-occipital, inferior longitudinal, and inferior fronto-occipital fascicule, thalamic radiation, and corona radiata. We conclude that distinct cortical regions control attention (a) across space (using an egocentric frame of reference) and (b) within objects (using an allocentric frame of reference), while common cortical regions (TPJ, IPS) and common white matter pathways support interactions across the different cortical regions.     

The effect of musical training on the neural correlates of math processing: a functional magnetic resonance imaging study in humans

The neural correlates of the previously hypothesized link between formal musical training and mathematics performance are investigated using functional magnetic resonance imaging (fMRI). FMRI was performed on fifteen normal adults, seven with musical training since early childhood, and eight without, while they mentally added and subtracted fractions. Musical training was associated with increased activation in the left fusiform gyrus and prefrontal cortex, and decreased activation in visual association areas and the left inferior parietal lobule during the mathematical task. We hypothesize that the correlation between musical training and math proficiency may be associated with improved working memory performance and an increased abstract representation of numerical quantities.     

Repetitive transcranial magnetic stimulation induces different responses in different cortical areas: a functional magnetic resonance study in humans

Repetitive transcranial magnetic stimulation (TMS) for 1 s at 4 Hz and 150% of the individual motor threshold was applied to primary motor cortex and adjacent cortical regions where no motor response could be produced. The hemodynamic reaction was measured using an event-related functional magnetic resonance setup. While all volunteers showed a typical signal increase beneath the coil during motor cortex stimulation, no consistent signal changes were present during frontal or parietal stimulation apart from activation of auditory cortex. The results suggest that neuronal stimulation by TMS is followed by an inhibitive phase that compensates for the effect of an initial neuronal activation. It is further concluded that the signal increases during motor cortex fit a sensory feedback from the moving body parts.     

Activation of the hippocampal formation by vestibular stimulation: a functional magnetic resonance imaging study

Functional MRI (f-MRI) is a non-invasive technique developed to permit functional mapping of the brain with a better temporal and spatial resolution than that offered by PET techniques. In our study, f-MRI was performed using blood oxygenation level dependent (BOLD) contrast imaging based on the magnetic properties of hemoglobin. This method relies on changes in the blood supply to the brain that accompany sensory stimulation or changes in cognitive state. All the images were obtained at 1.5 T on a Signa GEMS without ultrafast imaging. The vestibular stimulation was cold irrigation of the external auditory meatus (caloric stimulation). A population of normal healthy volunteers without a history of vestibular dysfunction was studied. The hippocampal formation as well as the retrosplenial cortex and the subiculum were activated by vestibular stimulation, suggesting that this activation may be related to spatial disorientation and a sensation of self-rotation experienced by the subjects during vestibular stimulation. The other results are similar to those obtained using PET.     

Noxious hot and cold stimulation produce common patterns of brain activation in humans: a functional magnetic resonance imaging study

We used functional magnetic resonance imaging (fMRI) to determine whether similar brain regions activate during noxious hot and cold stimulation. Six male subjects underwent whole brain fMRI during phasic delivery of noxious hot (46 degrees C) and noxious cold (5 degrees C) stimulation to the dorsum of the left hand. Mid-brain regions activated included thalamus, basal ganglia and insula. Cortical areas activated included cingulate, somatosensory, premotor and motor cortices, as well as prefrontal and inferior parietal cortex. Most regions activated bilaterally but with stronger activation contralateral to the stimulus. Noxious cold stimulation produced significantly increased volumes of activation compared to noxious heat in prefrontal areas only. Our results suggest a similar network of regions activate common to the perception of pain produced by either noxious hot or cold stimulation.     

Neural correlates of spatial working memory in humans: a functional magnetic resonance imaging study comparing visual and tactile processes

Recent studies of neural correlates of working memory components have identified both low-level perceptual processes and higher-order supramodal mechanisms through which sensory information can be integrated and manipulated. In addition to the primary sensory cortices, working memory relies on a widely distributed neural system of higher-order association areas that includes posterior parietal and occipital areas, and on prefrontal cortex for maintaining and manipulating information. The present study was designed to determine brain patterns of neural response to the same spatial working memory task presented either visually or in a tactile format, and to evaluate the relationship between spatial processing in the visual and tactile sensory modalities. Brain activity during visual and tactile spatial working memory tasks was measured in six young right-handed healthy male volunteers by using functional magnetic resonance imaging. Results indicated that similar fronto-parietal networks were recruited during spatial information processing across the two sensory modalities-specifically the posterior parietal cortex, the dorsolateral prefrontal cortex and the anterior cingulate cortex. These findings provide a neurobiological support to behavioral observations by indicating that common cerebral regions subserve generation of higher order mental representations involved in working memory independently from a specific sensory modality.     

Looking for the lunate sulcus: a magnetic resonance imaging study in modern humans

The position of the lunate sulcus in fossil endocasts (when it can be determined) may serve as a potential marker of cognitive development in extinct hominid species. While the lunate sulcus is reliably present in the brains of great apes and forms the anterolateral boundary of the primary visual cortex, in humans its presentation is much more variable, and even if present, it does not correspond to a functional region. Grafton Elliot Smith, who named the lunate sulcus, claimed that it was homologous in humans and the great apes. Using high-resolution MRI, we assessed the presence/absence and course of the lunate sulcus in 110 adult subjects. We found that in the vast majority of cases, lunate sulci identified on the surface of the occipital lobe are actually composed of smaller sulcal segments that converge into an apparently continuous composite lunate sulcus. We found only 3 examples in 220 hemispheres (1.4%) of continuous lunate sulci that resembled ape lunates in form (albeit in a more posterior position). Composite lunate sulci were found in 32.7% of left hemispheres and 26.4% of right hemispheres. These results, combined with those from histological and functional imaging studies, indicate that human and ape lunate sulci are not homologous structures. We suggest that the extent of functional reorganization of the occipital region during hominid evolution has been underestimated, and that changes in this region were not just passively shaped by expansion of parietal association cortex.     

The effect of transient hypercapnia on task-related changes in cerebral blood flow and blood oxygenation in awake normal humans: a functional magnetic resonance imaging study

It has recently been reported in alpha-chloralose anesthetized rats that the hemodynamic response to somatosensory stimulation almost doubled following transient hypercapnia (THC). In principle, this effect could be employed to enhance the sensitivity of perfusion-based fMRI experiments. To investigate whether a comparable effect was detectable in awake normal humans, changes in cerebral blood flow (DeltaCBF) and the effective transverse relaxation time (DeltaT(2)*) induced by a visual search task were measured in 10 healthy volunteers before and after THC. Concerning DeltaT(2)* no significant differences were found, whereas in four subjects DeltaCBF was significantly decreased (p < 0.01) following THC. These results demonstrate no increase in the CBF response following THC for awake humans. We conclude that the most likely explanation for this discrepancy with the earlier results obtained with animals is an as yet unknown mechanism of modulation of the cholinergic system by the anesthesia.     

Differential cerebellar activation related to perceived pain intensity during noxious thermal stimulation in humans: a functional magnetic resonance imaging study

Little is known about the cerebellar involvement in pain processing in spite of the fact that the cerebellum probably plays a crucial role in pain-related behavior. Using functional magnetic resonance imaging we examined the differential cerebellar activation in 18 healthy subjects in relation to their perceived pain-intensity of noxious and non-noxious thermal stimuli. In contrast to non-noxious (40 degrees C) stimuli, noxious (48.5 degrees C) stimuli revealed activation in the deep cerebellar nuclei, anterior vermis and bilaterally in the cerebellar hemispheric lobule VI. With the same noxious stimulus (48.5 degrees C) there was differential cerebellar activation depending on the perceived pain intensity: high pain intensity ratings were associated with activation in ipsilateral hemispheric lobule III-VI, deep cerebellar nuclei and in the anterior vermis (lobule III). This differential cerebellar activation pattern probably reflects not only somatosensory processing but also perceived pain intensity that may be important for cerebellar modulation of nociceptive circuits.     

Differential activity in the premotor cortex subdivisions in humans during mental calculation and verbal rehearsal tasks: a functional magnetic resonance imaging study

To investigate a possible role of the lateral premotor cortex in human cognitive processes, we compared brain activity during mental-operation numeral (MO-numeral) and verbal rehearsal (VR) tasks, using block-design functional MRI. Sixteen healthy subjects serially added a series of single-digit numbers during the MO-numeral task and silently rehearsed a memorized seven-digit number during the VR task. Each task condition was contrasted with a visual fixation task. Both MO-numeral and VR tasks revealed activity within the lateral premotor cortex among others. The rostral and dorsal part of the lateral premotor cortex (PMdr) showed significantly greater activity during the MO-numeral task than the VR task whereas its caudal part (PMdc) was similarly active during the two tasks. The present study suggests that the PMdr and PMdc are involved in different non-motor cognitive processes.     

Neural mechanisms of Korean word reading: a functional magnetic resonance imaging study

The use of functional magnetic resonance imaging permits the collection of brain activation patterns when native Korean speakers (12 persons as subjects) read Korean words and Chinese characters. The Korean language uses both alphabetic Korean words and logographic Chinese characters in its writing system. Our experimental results show that the activation patterns obtained for reading Chinese characters by Korean native speakers involve neural mechanisms that are similar to Chinese native speakers; i.e. strong left-lateralized middle frontal cortex activation. For the case of Korean word reading, the activation pattern in the bilateral fusiform gyrus, left middle frontal gyrus, left superior temporal gyrus, right mid temporal gyrus, precentral gyrus, and insula was observed. This suggests that the activation pattern for Korean word reading appears to corroborate with that of alphabetic words at the general level. A further noteworthy finding of our study is the strong activation of the posterior part of the right dorsolateral prefrontal cortex (BA 8). The right hemispheric BA 8 belongs to the visual higher order control area and we propose that this area should be responsible for processing of visuospatial (surface form) information of Korean words.     

Depression symptoms and cognitive control of emotion cues: a functional magnetic resonance imaging study

Few studies have examined associations between depressive symptoms and alterations in neural systems that subserve cognitive control. Cognitive control was assessed with an exogenous cueing task using happy, sad, and neutral facial expressions as cues among women with mild to moderate symptoms of depression and a non-depressed control group while functional magnetic resonance imaging (fMRI) measured brain activity. Amygdala and medial/orbital prefrontal cortex (PFC) response to valid emotion cues did not differ as a function of depression symptoms. However, significant depression group differences were observed when task demands required cognitive control. Participants with elevated depression symptoms showed weaker activation in right and left lateral PFC and parietal regions when shifting attentional focus away from invalid emotion cues. No depression group differences were observed for invalid non-emotional cues. Findings suggest that mild to moderate depression symptoms are associated with altered function in brain regions that mediate cognitive control of emotional information.     

Pattern of cortical reorganization in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study

Depending on individual lesion location and extent, reorganization of the human motor system has been observed with a high interindividual variability. In addition, variability of forces exerted, of motor effort, and of movement strategies complicates the interpretation of functional imaging studies. We hypothesize that a general pattern of reorganization can be identified if a homogeneous patient population is chosen and experimental conditions are controlled. Patients with amyotrophic lateral sclerosis (ALS) and healthy volunteers were trained to perform a simple finger flexion task with 10% of each individual's maximum grip force with constant movement amplitude and frequency. The activation pattern in ALS patients was distinctly different to that in healthy controls: In ALS patients, motor cortex activation was located more anteriorly, encompassing the premotor gyrus. The cluster volume within the supplementary motor area (SMA) was higher and shifted toward the pre-SMA. Contralateral inferior area 6 and bilateral parietal area 40 revealed higher cluster volumes. Our results demonstrate a general pattern of functional changes after motor neuron degeneration. They support the concept of a structurally parallel and functionally specialized organization of voluntary motor control. Degeneration of the first and second motor neurons leads to enhanced recruitment of motor areas usually involved in initiation and planning of movement. Partial compensation between functionally related motor areas seems to be a strategy to optimize performance if the most efficient pathway is unavailable.     

Neuronal substrates of haptic shape encoding and matching: a functional magnetic resonance imaging study

We used functional magnetic resonance imaging to differentiate cerebral areas involved in two different dimensions of haptic shape perception: encoding and matching. For this purpose, healthy right-handed subjects were asked to compare pairs of complex 2D geometrical tactile shapes presented in a sequential two-alternative forced-choice task. Shape encoding involved a large sensorimotor network including the primary (SI) and secondary (SII) somatosensory cortex, the anterior part of the intraparietal sulcus (IPA) and of the supramarginal gyrus (SMG), regions previously associated with somatosensory shape perception. Activations were also observed in posterior parietal regions (aSPL), motor and premotor regions (primary motor cortex (MI), ventral premotor cortex, dorsal premotor cortex, supplementary motor area), as well as prefrontal areas (aPFC, VLPFC), parietal-occipital cortex (POC) and cerebellum. We propose that this distributed network reflects construction and maintenance of sensorimotor traces of exploration hand movements during complex shape encoding, and subsequent transformation of these traces into a more abstract shape representation using kinesthetic imagery. Moreover, haptic shape encoding was found to activate the left lateral occipital complex (LOC), thus corroborating the implication of this extrastriate visual area in multisensory shape representation, besides its contribution to visual imagery. Furthermore, left hemisphere predominance was shown during encoding, whereas right hemisphere predominance was associated with the matching process. Activations of SI, MI, PMd and aSPL, which were predominant in the left hemisphere during the encoding, were shifted to the right hemisphere during the matching. In addition, new activations emerged (right dorsolateral pre-frontal cortex, bilateral inferior parietal lobe, right SII) suggesting their specific involvement during 2D geometrical shape matching.     

The left parietal cortex and motor intention: an event-related functional magnetic resonance imaging study

Traditionally the posterior parietal cortex was believed to be a sensory structure. More recently, however, its important role in sensory-motor integration has been recognized. One of its functions suggested in this context is the forming of intentions, i.e. high-level cognitive plans for movements. The selection and planning of a specific movement defines motor intention. In this study we used rapid event-related functional magnetic resonance imaging of healthy human subjects to investigate the involvement of posterior parietal cortex in motor intention in response to valid imperative cues. Subjects were provided with either neutral, motor or spatial cues. Neutral cues simply alerted, motor cues indicated which hand to use for response, and spatial cues indicated on which side the target would appear. Importantly, identical targets and responses followed these cues. Therefore any differential neural effects observed are independent from the actual movement performed. Differential blood oxygen level dependent signal changes for motor vs. neutral as well as motor vs. spatial cue trials were found in the left supramarginal gyrus, as hypothesized. The results demonstrate that neural activity in the left supramarginal gyrus underlies motor plans independent from the execution of the movement and thus extend previous neuropsychological and functional imaging data on the role of the left supramarginal gyrus in higher motor cognition.     

The neural correlates of reward-related processing in major depressive disorder: A meta-analysis of functional magnetic resonance imaging studies

Background

A growing number of functional magnetic resonance imaging (fMRI) studies have been conducted in major depressive disorder (MDD) to elucidate reward-related brain functions. The aim of this meta-analysis was to examine the common reward network in the MDD brain and to further distinguish the brain activation patterns between positive stimuli and monetary rewards as well as reward anticipation and outcome.

Methods

A series of activation likelihood estimation (ALE) meta-analyses were performed across 22 fMRI studies that examined reward-related processing, with a total of 341 MDD patients and 367 healthy controls.

Results

We observed several frontostriatal regions that participated in reward processing in MDD. The common reward network in MDD was characterized by decreased subcortical and limbic areas activity and an increased cortical response. In addition, the cerebellum, lingual gyrus, parahippocampal gyrus and fusiform gyrus preferentially responded to positive stimuli in MDD, while the insula, precuneus, cuneus, PFC and inferior parietal lobule selectively responded to monetary rewards. Our results indicated a reduced caudate response during both monetary anticipation and outcome stages as well as increased activation in the middle frontal gyrus and dorsal anterior cingulate during reward anticipation in MDD.

Limitations

The reward-related tasks and mood states of patients included in our analysis were heterogeneous.

Conclusions

Our current findings suggest that there exist emotional or motivational pathway dysfunctions in MDD during reward-related processing. Future studies may be strengthened by paying careful attention to the types of reward used as well as the different components of reward processing examined.     

Functional and structural aging of the speech sensorimotor neural system: functional magnetic resonance imaging evidence

The ability to perceive and produce speech undergoes important changes in late adulthood. The goal of the present study was to characterize functional and structural age-related differences in the cortical network that support speech perception and production, using magnetic resonance imaging, as well as the relationship between functional and structural age-related changes occurring in this network. We asked young and older adults to observe videos of a speaker producing single words (perception), and to observe and repeat the words produced (production). Results show a widespread bilateral network of brain activation for Perception and Production that was not correlated with age. In addition, several regions did show age-related change (auditory cortex, planum temporale, superior temporal sulcus, premotor cortices, SMA-proper). Examination of the relationship between brain signal and regional and global gray matter volume and cortical thickness revealed a complex set of relationships between structure and function, with some regions showing a relationship between structure and function and some not. The present results provide novel findings about the neurobiology of aging and verbal communication.     

The amygdala in schizophrenia: a trimodal magnetic resonance imaging study

In schizophrenic psychoses, structural and functional alterations of the amygdala have been demonstrated by several neuroimaging studies. However, postmortem examinations on the brains of schizophrenics did not confirm the volume changes reported by volumetric magnetic resonance imaging (MRI) studies. In order to address these contradictory findings and to further elucidate the possibly underlying pathophysiological process of the amygdala, we employed a trimodal MRI design including high-resolution volumetry, diffusion tensor imaging (DTI), and quantitative magnetization transfer imaging (qMTI) in a sample of 14 schizophrenic patients and 14 matched controls. Three-dimensional MRI volumetry revealed a significant reduction of amygdala raw volumes in the patient group, while amygdala volumes normalized for intracranial volume did not differ between the two groups. The regional diffusional anisotropy of the amygdala, expressed as inter-voxel coherence (COH), showed a marked and significant reduction in schizophrenics. Assessment of qMTI parameters yielded significant group differences for the T2 time of the bound proton pool and the T1 time of the free proton pool, while the semi-quantitative magnetization transfer ratio (MTR) did not differ between the groups. The application of multimodal MRI protocols is diagnostically relevant for the differentiation between schizophrenic patients and controls and provides a new strategy for the detection and characterization of subtle structural alterations in defined regions of the living brain.