Regional brain activity associated with visual backward masking

In visual backward masking, the visibility of a briefly presented visual target is disrupted by a mask that is presented shortly thereafter. The goal of the current study was to identify regions in the human cortex that may provide the neural basis of visual masking. We searched for areas whose activity correlated with perception as we systematically varied the strength of masking. A total of 13 subjects performed a backward masking task during functional magnetic resonance imaging. Target and mask were presented at three delay intervals (34, 68, and 102 msec) and behavioral measures confirmed that the targets were more visible at longer masking intervals. Two sets of regions of interest were identified: Distinct regions in the visual cortex (V1/V2, LO, hMT+) were segregated using scans to localize visual processing drawn from the existing literature. Additional cortical regions were selected in a data-driven approach based on their activity during the backward masking task. For each set, we determined the regions whose magnitude of activation increased at longer masking intervals. Nine of the subjects provided valid behavioral performance data on the visual masking task and imaging data from these subjects were used for subsequent analysis. The scans of visual processing areas identified four regions, including: early visual areas (V1 and V2), the motion-sensitive regions in the lateral occipital (LO) lobe (hMT+), and two components (dorsal and ventral) of the object-sensitive region, LO. Of these, the ventral and dorsal LO regions were sensitive to the strength of the mask. For the data-driven approach, six regions were identified on the basis of a difference map in which all masking intervals were contrasted with rest. These included the inferior parietal, anterior cingulate, precentral, insula, thalamic, and occipital areas. The predicted effects of more activity with weaker masking were seen in the thalamus, inferior parietal, and anterior cingulate. This study isolated three types of visual processing areas. The first included regions that subserve key stages of vision (including object and motion processing). The second type responded to the presentation of brief ly presented visual stimuli, regardless of masking interval. The third type (selected from the first two) included regions sensitive to the interval between the target and mask. These latter regions (including ventral LO, inferior parietal, anterior cingulate, and thalamus) may form the neural substrate of backward masking.     

Regional differences in the development of cholecystokinin-like activity in rat brain

The postnatal development of cholecystokinin (CCK) in rat brain was studied by radioimmunoassay and bioassay of tissue extracts. Marked differences were found in the patterns of development in different regions of the brain. In the cerebellum and brainstem of newborn rats the concentrations of CCK8-like immunoreactivity were 40-100% those in adults, whereas in more rostral regions the concentrations were 1-10% of those in adults. Between 0 and 14 days in concentrations of CCK-like activity measured by radioimmunoassay increased up to 30-fold in hypothalamus, cortex and olfactory bulb; in the cortex there were further increases up to 42 days. Cortical CCK was also measured by bioassay on rabbit gall bladder in vitro; bioactivity was identified in foetuses, and after birth showed a similar pattern of increase to that measured by radioimmunoassay. Immunoreactive material in extracts of neonatal cerebellum, brainstem and cortex was identified as CCK8 on the basis of cross-reactivity with different antisera, and chromatographic properties on gel filtration. The results raise the possibility of different rates of maturation of central CCKergic systems.     

Regional brain activity during shape recognition impaired by a scopolamine challenge to encoding

In the present positron emission tomography (PET) study, we examine the effect of a scopolamine-induced challenge to encoding upon the pattern of regional cerebral blood flow during recognition of a list of abstract visual shapes 3 days after encoding of these shapes. This study was conducted to test hypotheses concerning the fusiform and thalamic contributions to object recognition arising from a previous imaging study of impaired recognition. In that study, we demonstrated that activity in the fusiform cortex and the thalamus during shape recognition was modulated by memory challenges. These memory challenges included, on one hand, impaired storage as a consequence of diazepam administration during encoding, and, on the other hand, impaired retrieval caused by a perceptual challenge. Activation in the fusiform cortex decreased during impaired recognition, irrespective of the type of challenge. In contrast, thalamic activation increased only when the recognition deficit resulted from impaired memory storage. Based on these results, we hypothesized that fusiform activation during recognition reflects the matching of an incoming stimulus with a stored one, whereas thalamic activation reflects retrieval attempts. These hypotheses would receive considerable support if scopolamine, which also impairs memory storage, induced similar modulations of fusiform and thalamic activation. In the present study, we observed that a scopolamine challenge to encoding does indeed modulate the activity in the very same regions that were previously modulated by a diazepam challenge. Hence, a similar memory deficit, although primarily effected through different neurochemical pathways, was paralleled by a similar modulation of activity in the same set of nodes in the shape recognition network. In the fusiform cortex, scopolamine decreased recognition-related activity, as did the sensory challenge of retrieval. Furthermore, covariate analysis demonstrated that the level of fusiform activity linearly correlates with behavioural performance. In the thalamus, activation increased following impaired encoding. This is in accordance with the idea that enhanced thalamic activity reflects increased effort expended in retrieval. In addition, in the intraparietal sulcus, differential activation also increased following impaired memory storage, possibly reflecting enhanced visuospatial attention in an effort to compensate for impaired performance.     

Dyslexia: Regional differences in brain electrical activity by topographic mapping

Electroencephalographic (EEG) and evoked potential data were recorded during behavioral testing from 8 dyslexic and 10 normal boys aged 9 to 11 years. Topographic mapping of their brain electrical activity revealed four discrete regions of difference between the two groups involving both hemispheres, left more than right. Aberrant dyslexic physiology was not restricted to a single locus but was found in much of the cortical region ordinarily involved in reading and speech. Prominent group differences were observed in the bifrontal area in addition to the more expected left temporal and left posterior quadrant regions. Although activation tests produced more prominent group difference, dyslexics differed from normal subjects at rest as well. EEG alpha activity was increased for the dyslexics, suggesting relative cortical inactivity in that group.     

Regional brain variations of cytochrome oxidase activity in Relnrl-orl mutant mice

Cell malpositioning has been described in laminated structures of the spontaneous mutation, reeler, including the cerebellum, the hippocampus, and the neocortex. Despite the ectopic positions of different neuronal populations, the specificity of synaptic connections is maintained. The metabolic consequences of this form of neuropathology were examined in Reln(rl) mutant mice by quantitative measures of cytochrome oxidase (CO) activity, a mitochondrial enzyme essential for oxidative metabolism in neurons. Despite severe tissue disorganization but in line with the intact synaptic organization, the reeler mutation did not affect global metabolic activity of the laminated structures of the brain. CO activity, however, was altered in specific subregions of the cerebellum, hippocampus, and neocortex, as well as in septum and various brainstem (medial pontine, paramedial reticular, paragigantocellular reticular) regions anatomically related to these structures, attesting to large functional alterations in Reln(rl-orl) brain. Metabolic activity variations were also detected in the ventral tegmental area and ventral neostriatum of the mesolimbic dopaminergic pathway. The results are discussed and compared to the regional CO variations found in other ataxic mice, in regard to the structural defects, the integrity of the connections, and the mutation-specific effects.     

Regional distribution and control of tyrosine hydroxylase activity in the quail brain

Tyrosine hydroxylase (TH) activity, the rate-limiting step in the synthesis of catecholamines, was quantified in the preoptic area-hypothalamus of adult male Japanese quail by a new assay measuring the tritiated water production from 3,5-[3H]-L-tyrosine. Maximal levels of activity were observed at a 20-25 microM concentration of substrate, with more than 50% inhibition of the activity being recorded at a 100 microM concentration. TH activity was linear as a function of the incubation time during the first 20 min and maximal at a pH of 6.0. TH was heterogeneously distributed in the quail brain with highest levels of activity being found (in decreasing order) in the mesencephalon, diencephalon, and telencephalon. Given the large size of the telencephalon, this is the brain area that contains, as a whole, the highest level of enzyme activity. TH inhibitors that have been well-characterized in mammals, such as 3-iodo-L-tyrosine and L-alpha-methyl-p-tyrosine (AMPT) completely inhibited the enzyme activity at a 100 microM concentration. In mammals, the accumulation of catecholamines exerts a negative feedback control on TH activity. Similar controls were observed in the quail brain. Two inhibitors of the DOPA decarboxylase that should lead to accumulation of DOPA depressed TH activity by 60% or more, and the inhibitor of the dopamine beta-hydroxylase, fusaric acid that should cause an accumulation of dopamine, suppressed 90% of the TH activity. The addition of exogenous DOPA, dopamine, or norepinephrine to the brain homogenates also strongly inhibited TH activity, independently confirming the feedback effects of the enzyme products on the enzyme activity. These data demonstrate that TH activity in the quail brain is heterogeneously distributed and acutely regulated, as it is in mammals, by the accumulation of its products and of the derived catecholamines.     

Regional and subcellular distribution of Met- and Leu-enkephalin-degrading activity in rat brain

Met- and Leu-enkephalin were degraded rapidly by brain aminopeptidases with the K_m's 9.1 mM and 5.7 mM respectively; the V_max, 100 μmol/mg protein per min for Met-enkephalin and 50 μmol/mg protein per min for Leu-enkephalin. The major product for Met-enkephalin was des-Tyr-Met-enkephalin. The enkephalin-degrading activity (EDA) in the brain was 16-fold higher than in plasma and was 15% of that in the kidney. The hydrolytic activity was heterogeneous in rat brain regions. For Met-enkephalin, the activity in decreasing order was striatum, hypothalamus, hippocampus, cerebellum, cortex, mid-brain, and medulla oblongata; for Leu-enkephalin the order was hippocampus, striatum, mid-brain, cortex, hypothalamus, cerebellum, and medulla oblongata. The subcellular distribution of the EDA in the whole brain, the hippocampus, and the striatum was similar, with the soluble fraction having the highest, the synaptosomal fraction the lowest, activity. The distribution of EDA was different from the arylamidase activity with Tyr-β-naphthylamide and Leu-β-naphthylamide as substrates. Our results indicate that a group of aminopeptidases is responsible for the degradation of both enkephalins.     

Regional brain activity during transient self-induced anxiety and anger in healthy adults.

BACKGROUND: Several studies have demonstrated that transient self-induced sadness activates anterior paralimbic structures. To further examine the specificity of these findings and the neural substrates involved in anger and anxiety, we studied the neural correlates of the induction of anxiety and anger in healthy adults. METHODS: We used H2(15)O and positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in 16 healthy adults during the induction of transient anxiety, anger, and neutral emotions. Subjects achieved differential emotions by recalling prior life events while viewing affect-appropriate faces. RESULTS: Both the anxiety and anger conditions were associated with increased normalized rCBF in left inferior frontal and left temporal pole regions and decreased rCBF in right posterior temporal/parietal and right superior frontal cortex, compared to the neutral induction. Additionally, compared to neutral induction, anxiety was associated with increased rCBF in the left anterior cingulate and cuneus and decreased rCBF in right medial frontal cortex, while the anger induction was uniquely associated with increased rCBF in right temporal pole and thalamus. CONCLUSIONS: Self-generated transient states of anxiety and anger are associated with both overlapping and distinct regional brain activity patterns and provide a template for further dissection of specific components of normal and pathologic emotions.     

Reward and motivation systems: a brain mapping study of early-stage intense romantic love in Chinese participants

Early‐stage romantic love has been studied previously in the United States and United Kingdom (Aron et al. [ 2005 ]: J Neurophysiol 94:327–337; Bartels and Zeki [ 2000 ]: Neuroreport 11:3829–3834; Ortigue et al. [ 2007 ]: J Cogn Neurosci 19:1218–1230), revealing activation in the reward and motivation systems of the brain. In this study, we asked what systems are activated for early‐stage romantic love in Easterners, specifically Chinese participants? Are these activations affected by individual differences within a cultural context of Traditionality and Modernity? Also, are these brain activations correlated with later satisfaction in the relationship? In Beijing, we used the same procedure used by Aron et al. (Aron et al. [ 2005 ]: J Neurophysiol 94:327–337). The stimuli for 18 Chinese participants were a picture of the face of their beloved, the face of a familiar acquaintance, and a countback task. We found significant activations specific to the beloved in the reward and motivation systems, particularly, the ventral tegmental area and the caudate. The mid‐orbitofrontal cortex and cerebellum were also activated, whereas amygdala, medial orbitofrontal, and medial accumbens activity were decreased relative to the familiar acquaintance. Self‐reported Traditionality and Modernity scores were each positively correlated with activity in the nucleus accumbens, although in different regions and sides of the brain. Activity in the subgenual area and the superior frontal gyrus was associated with higher relationship happiness at 18‐month follow‐up. Our results show that midbrain dopamine‐rich reward/motivation systems were activated by early‐stage romantic love in Chinese participants, as found by other studies. Neural activity was associated with Traditionality and Modernity attitudes as well as with later relationship happiness for Chinese participants. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Binding of angiotensins to rat brain tissue: Structure activity relationship

The binding of ³H-angiotensin II to a synaptosome-enriched fraction of the subcortical part of rat brain was studied. In this fraction specific high-affinity binding sites for angiotensin II were demonstrated. The binding sites were saturated at a ligand concentration of 2×10⁻⁹ M. Scatchard analysis revealed a single class of binding sites with an apparent maximal binding capacity of 14 fmoles/mg of protein and an equilibrium dissociation constant, K_d, of 0.9 × 10⁻⁹ M. The specific binding at the K_d concentration amounted to 59% of the total binding and was reversible. The association and dissociation rate constants (k₁ and k₋₁) were 0.0212 nM⁻¹ min⁻¹ and 0.0196 min⁻¹, respectively. Binding was dependent on both incubation time and tissue concentration in the incubation mixture. Angiotensins with biological activity in the brain, i.e., angiotensins I, II, III, and the fragments (3–8) and (4–8) competed with ³H-angiotensin II for the binding sites with IC₅₀'s of 9×10⁻⁸ M, 2×10⁻⁹ M, 4× 10⁻⁹ M, 4× 10⁻⁷ M and 4×10⁻⁶, respectively. In the presence of 1 mM of the converting enzyme inhibitor SQ 14,225 the IC₅₀ for angiotensin I was 2 × 10⁻⁷ M. Competition by the biologically active fragment angiotensin (5–8) could not be demonstrated. The latter peptide, however, was highly metabolized during the incubation under the assay conditions used. The binding potency of the various angiotensins paralleled their dipsogenic and presser potency. The present data indicate the possible physiological involvement of these binding sites as specific receptors in the actions of angiotensins in the brain.     

Regional distribution of soluble calcium activated proteinase activity in neonatal and adult rat brain

Calcium dependent proteolytic activity in the soluble fraction of various rat brain regions was assayed using 14C-radiolabelled denatured casein as a substrate. Two forms of activity, distinguishable by their calcium requirement for half maximal activation (5 and 80 microM), were found; both were blocked by sulfhydryl alkylating agents and thiol proteinase inhibitors. Preincubation at 58 degrees C for 10 min also eliminated the high threshold activity. These characteristics are identical to those reported for calcium activated neutral proteinases ('calpains') found in other tissues. Calpain activity varied markedly across brain regions. The greatest values for the high threshold enzyme were found in pons-medulla followed by cerebellum/mesencephalon and finally the telencephalon. The low threshold enzyme had low levels of activity throughout the brainstem and diencephalon and was barely detectable in telencephalic structures. In contrast, a previously described endogenous inhibitor of calpain, 'calpastatin', was found not to vary in its activity across brain regions. Calpain activity was high in the prenatal brain, but while the hindbrain maintained high levels of activity into adulthood, the activity in the forebrain dropped 80% during the early postnatal period. The differences between forebrain and hindbrain activity levels were evident during the first 5 days of the neonatal period, suggesting that glial cell differentiation is not responsible for the regional variations found in the adult. These results are discussed with regard to the possibility that the turnover of anatomical structures differs between brain regions.     

Emotion regulation modulates anticipatory brain activity that predicts emotional memory encoding in women

It has been shown that the effectiveness with which unpleasant events are encoded into memory is related to brain activity set in train before the events. Here, we assessed whether encoding-related activity before an aversive event can be modulated by emotion regulation. Electrical brain activity was recorded from the scalps of healthy women while they performed an incidental encoding task on randomly intermixed unpleasant and neutral visual scenes. A cue presented 1.5 s before each picture indicated the upcoming valence. In half of the blocks of trials, the instructions emphasized to let emotions arise in a natural way. In the other half, participants were asked to decrease their emotional response by adopting the perspective of a detached observer. Memory for the scenes was probed 1 day later with a recognition memory test. Brain activity before unpleasant scenes predicted later memory of the scenes, but only when participants felt their emotions and did not detach from them. The findings indicate that emotion regulation can eliminate the influence of anticipatory brain activity on memory encoding. This may be relevant for the understanding and treatment of psychiatric diseases with a memory component.     

Periodic activity in cerebral arousal mechanisms--the relationship to sleep and brain damage.

Periodic activity during light sleep is well recognised in many physiological systems, particularly respiration. In damaged brains this activity can become exaggerated. It involves the autonomic nervous system, the muscles, the cerebrospinal fluid (CSF) pressure, the cerebral blood flow and the electroencephalogram (EEG). It is related to the level of arousal. The EEGs of 52 subjects were studied. In stage 0-1 sleep, periods of alpha activity alternated with periods of theta activity related to the level of arousal. The intervals between the alpha onsets were measured and the data pooled. There was a dominant interval of about 16 sec. It is suggested that this is a physiological cerebral rhythm involving the cortex and the brain-stem activating mechanisms, responsive to outside stimuli but essentially endogenous. It is related to the controls of the autonomic, motor, and some cerebral auto-regulatory mechanisms. It may be severely disturbed in brain damage.     

Regional brain metabolism in a murine systemic lupus erythematosus model

Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and anti-nuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb+ mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood–brain barrier (BBB) breach. In DNRAb+ mice, metabolism declined at the site of BBB breach in the first 2 weeks and increased over the next 2 weeks. In contrast, DNRAb− mice exhibited metabolic increases in these regions over the 4 weeks after the insult. Memory impairment was present in DNRAb+ animals with hippocampal BBB breach and altered fear conditioning in DNRAb+ mice with amygdala BBB breach. In DNRAb+ mice, we observed an inverse relationship between neuron number and regional metabolism, while a positive correlation was observed in DNRAb− mice. These findings suggest that local metabolic alterations in this model take place through different mechanisms with distinct time courses, with important implications for the interpretation of imaging data in SLE subjects.     

Regional patterns of brain activity in adults with a history of childhood-onset depression: gender differences and clinical variability

OBJECTIVE: The study investigated the hypothesis that EEG asymmetry scores (indicating higher right and lower left frontal brain activity) are associated with vulnerability to negative mood states and depressive disorders. Gender and clinical history variables were examined as factors that may influence the relation between EEG and depression. METHOD: EEG measures of asymmetrical alpha frequency (7.5-12.5 Hz) suppression were analyzed in 55 young adults with a documented clinical history of childhood-onset depression and 55 comparison subjects with no history of major psychopathology. EEG patterns were examined in relation to operational diagnoses of mental disorders during childhood and adulthood. RESULTS: Differences in EEG asymmetry between childhood depression probands and comparison subjects varied with gender, diagnostic history, and current symptoms. Women with childhood depression had higher right midfrontal alpha suppression, and men with childhood depression had higher left midfrontal alpha suppression, relative to comparison subjects. At all scalp sites, women showed greater alpha power than men. Probands with a bipolar spectrum course had the most extreme midfrontal asymmetry. Frontal asymmetry was more extreme in probands with current depressive symptoms than in those without current symptoms. CONCLUSIONS: Regional brain activity is influenced by gender and variability in clinical course. The findings have implications for investigating brain correlates of mood disorder and may help to develop more refined phenotypes.     

Regional brain glucose metabolism in neuroacanthocytosis

Two brothers with neuroacanthocytosis had [18F]-2-fluoro-2-deoxyglucose PET scans showing marked glucose hypometabolism of the caudate and putamen. MRIs showed no evidence of atrophy or modification of signal intensity in these structures. Decreased glucose utilization of the striatum can underlie hyperkinetic movement disorders of various etiologies.     

Regional brain activity during tasks devoted to the central executive of working memory

Most previous PET studies investigating the central executive (CE) component of working memory found activation in the prefrontal cortex. However, the tasks used did not always permit to distinguish precisely the functions of the CE from the storage function of the slave systems. The aim of the present study was to isolate brain areas that subserve manipulation of information by the CE when the influence of storage function was removed. A PET activation study was performed with four cognitive tasks, crossing conditions of temporary storage and manipulation of information. The manipulation of information induced an activation in the right (BA 10/46) and left (BA 9/6) middle frontal gyrus and in the left parietal area (BA7). The interaction between the storage and manipulation conditions did not reveal any significant changes in activation. These results are in agreement with the hypothesis that CE functions are distributed between anterior and posterior brain areas, but could also reflect a simultaneous involvement of controlled (frontal) and automatic (parietal) attentional systems. In the other hand, the absence of interaction between the storage and manipulation conditions demonstrates that the CE is not necessarily related to the presence of a memory load.     

Regional distribution and time-course of calpain activation following kainate-induced seizure activity in adult rat brain

Systemic injection of kainic acid (KA) in adult rat elicits a pattern of neuronal pathology which exhibits several features of human temporal lobe epilepsy. KA-induced seizure activity is accompanied by the activation of the calcium-dependent protease calpain in limbic structures. In the present study, we evaluated the spatio-temporal activation of calpain after the onset of seizure activity by immunohistochemistry using an antibody for the spectrin breakdown product (sbdp) generated by calpain-mediated spectrin proteolysis. In addition, we compared the changes in sbdp immunoreactivity with those in immunoreactivity to subunits of the Glu/AMPA receptors (GluR₁ andGluR₂₃). One hour after seizure onset, sbdp accumulation was observed in selected interneurons in stratum oriens and in the hilus of the dentate gyrus. By 4 h, sbdp immunoreactivity was prominent in dendritic fields of the hippocampus as well as in neurons in thalamus and piriform cortex. By 8 h, sbdp immunoreactivity had disappeared from interneurons but was localized in pyramidal cell bodies in hippocampus. Intense labeling of cell bodies and dendritic fields persisted until 5 days following KA treatment. Changes in GluR subunit immunoreactivity were mirror images of those seen for sbdp. In general, increased sbdp immunoreactivity in dendritic fields was associated with decreased (GluR₁ immunoreactivity. However, increased sbdp immunoreactivity in neuronal perikarya was also associated with increased GluR immunoreactivity. These results indicate that calpain activation following seizure onset exhibits a specific spatio-temporal pattern, with activation in restricted interneurons preceding widespread activation in pyramidal neurons. Calpain activation also precedes neuronal pathology and could thus represent an initial trigger for neuronal pathology. Finally, the results suggest that calpain activation produces rapid alterations in GluR subunit properties which could be involved in the hyperexcitability observed following seizure activity.     

Regional brain superoxide dismutase activity is altered differently by heat in warm and cool mice

The significant regional variation in brain superoxide dismutase (SOD) activity was similar in mice from both warm and cool cohorts. Mice in the cool cohort generally had higher SOD activity, which varied significantly with body temperature in striatum and in preoptic area of the hypothalamus. Changes in SOD activity following heating were revealed only when warm and cool cohorts were analysed separately. SOD activity decreased significantly in striatum, hypothalamus, and hippocampus of the cool cohort only. The decline was to levels consistent with those of the warm cohort. Body temperature of cool mice increased more than that of warm mice following each increment of heating so resultant body temperatures became similar. The role of SOD as part of a differential defense against heat stress in warm and cool mice is presented.