We conducted two experiments to examine central processing of the taste of citric acid. In the first experiment, elevated citric acid recognition thresholds, but normal detection thresholds, were observed in a group of patients who had undergone a right anterior temporal lobectomy for the treatment of epilepsy, compared with a control group and a group of patients who had undergone the same operation in the left hemisphere. In the second study, using positron emission tomography, we compared regional cerebral blood flow (rCBF) in a condition in which citric acid was presented with one in which water was presented (with similar somatosensory stimulation across both conditions). We observed increased rCBF bilaterally in the caudolateral orbitofrontal cortex, in the right anteromedial temporal lobe, and in the right caudomedial orbitofrontal cortex. The elevated recognition thresholds exhibited in patients with resection of the right anteromedial temporal lobe may be accounted for by damage in an area corresp...

Uric acid (UA) is a purine metabolite that in most mammals is degraded by the hepatic enzyme uricase to allantoin. Epidemiological studies have shown that an elevated UA level predicts the development of cognition and memory deficits; however, there is no direct evidence of this relationship, and the underlying mechanism is largely undefined. Here, we show that a high-UA diet triggers the expression of proinflammatory cytokines, activates the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway, and increases gliosis in the hippocampus of Wistar rats. We, subsequently, identify a specific inhibitor of NF-κB, BAY11-7085, and show that stereotactic injections of the inhibitor markedly ameliorate UA-induced hippocampal inflammation and memory deficits in C57BL/6 mice. We also found that NF-κB is activated in the primary cultured hippocampal cells after UA administration. Additionally, C57BL/6 mice that lack TLR4 are substantially protected against UA-induced cognitive dysfunction, possibly due to a decr...

Unexpected and thus surprising events are omnipresent and oftentimes require adaptive behavior such as unexpected inhibition or unexpected action. The current theory of unexpected events suggests that such unexpected events just like global stopping recruit a fronto-basal-ganglia network. A global suppressive effect impacting ongoing motor responses and cognition is specifically attributed to the subthalamic nucleus (STN). Previous studies either used separate tasks or presented unexpected, task-unrelated stimuli during response inhibition tasks to relate the neural signature of unexpected events to that of stopping. Here, we aimed to test these predictions using a within task design with identical stimulus material for both unexpected action and unexpected inhibition using functional magnetic resonance imaging (fMRI) for the first time. To this end, 32 healthy human participants of both sexes performed a cue-informed go/nogo task comprising expected and unexpected action and inhibition trials during fMRI....

Structural asymmetries in the supratemporal plane of the human brain are often cited as the anatomical basis for the lateralization of language predominantly to the left hemisphere. However, similar asymmetries are found for structures mediating earlier events in the auditory processing stream, suggesting that functional lateralization may occur even at the level of primary auditory cortex. We tested this hypothesis using functional magnetic resonance imaging to evaluate human auditory cortex responses to monaurally presented tones. Relative to silence, tones presented separately to either ear produced greater activation in left than right Heschl's gyrus, the location of primary auditory cortex. This functional lateralization for primary auditory cortex is distinct from the contralateral dominance reported for other mammals, including nonhuman primates, and may have contributed to the evolution of a unique role for the left hemisphere in language processing.

Prior studies have used fMRI to measure the onset of neural activity from a stable baseline with a temporal precision on the order of 100 msec. Many important neural processes, however, reveal themselves as increases in activity that lie on top of another neural response. We attempted to determine whether fMRI could measure the timing of an increase that occurred 200 msec after initial response. Subjects viewed stimuli from three conditions. In our baseline condition, a low contrast flickering checkerboard was presented for 600 msec. We added a 400 msec contrast increment to this stimulus either at a 200 msec delay or immediately upon stimulus presentation; thus in the delay condition the low contrast checkerboard increased its contrast after 200 msec and remained high contrast for 400 msec, while in the immediate condition a high contrast flickering checkerboard reduced its contrast after 400 msec and remained low for 200 msec. We acquired BOLD fMR images every 100 msec (TR) while these conditions were pr...

Background: Neural networks are altered in many disorders, with implications on the affected region and connected areas. Connectivity atlases based on 2D serial sections are exceedingly valuable resources. However, they do not allow for 3D tractography ...

Successful communication between two people depends first on the recognition of the intention to communicate. Such intentions may be conveyed by signals directed at the self, such as calling a person's name or making eye contact. In this study we use functional magnetic resonance imaging to show that the perception of these two signals, which differ in modality and sensory channel, activate common brain regions: the paracingulate cortex and temporal poles bilaterally. These regions are part of a network that has been consistently activated when people are asked to think about the mental states of others. Activation of this network is independent of arousal as measured by changes in pupil diameter.

An impediment to the development of effective therapies for neurodegenerative disease is that available animal models do not reproduce important clinical features such as adult-onset and stereotypical patterns of progression. Using in vivo magnetic resonance imaging and behavioral testing to study male and female decrepit mice, we found a stereotypical neuroanatomical pattern of progression of the lesion along the limbic system network and an associated memory impairment. Using structural variant analysis, we identified an intronic mutation in a mitochondrial-associated gene ( Mrpl3 ) that is responsible for the decrepit phenotype. While the function of this gene is unknown, embryonic lethality in Mrpl3 knock-out mice suggests it is critical for early development. The observation that a mutation linked to energy metabolism precipitates a pattern of neurodegeneration via cell death across disparate but linked brain regions may explain how stereotyped patterns of neurodegeneration arise in humans or define a...

White matter (WM) pathologies have not been previously characterized in zQ175DN model, neither by MRI nor by histological means. Diffusion tensor imaging (DTI) allows for good differentiation of structures in the WM. Here we present high-resolution ex v...

Brain imaging studies have suggested regional reduction in gray matter content in bipolar patients in key anatomical regions involved in mood regulation. Most studies have utilized region-of-interest based methodologies, in which a particular brain structure is chosen a priori, traced, and then compared among different groups. As a different approach, voxel-based morphometry can potentially identify gray matter changes across the whole brain. We examined structural T1-weighted 1.5 T MR images of 26 bipolar disorder patients (age±S.D.= 35.2±10.4 years) and 39 healthy subjects (age±S.D.= 36.6±9.7 years). SPM99 was utilized to normalize the images to the MNI brain template, segment, smooth, and generate a statistical map of the differences between the groups, with age as covariate. Statistical significance was set at p<0.01 (voxel-level, uncorrected). Compared with the healthy control group, the bipolar subjects presented decreased gray matter density in an area in the left temporal lobe encompassing the limb...