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In daily communication, we sometimes use ironic expressions to convey the opposite meaning. To understand these contradictory statements, we have to infer contextual implications and the speaker's mental state. However, little is known about how our brains carry out these complex processes. In this study, we investigated the neural substrates involved in irony comprehension using echoic utterance (Sperber and Wilson, 1986, 1995). Participants read a short scenario that consisted of five sentences. The first four sentences explained the situation of the protagonists. The fifth connoted either an ironic, literal, or unconnected meaning. The participants had to press a button to indicate whether or not the final sentence expressed irony. In the ironic sentence condition, the bilateral superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, medial prefrontal cortex, superior temporal gyrus, inferior parietal lobule, caudate, thalamus, the left insula, and amygdala were activated. In the literal sentence condition, the right superior frontal gyrus, the bilateral middle frontal gyrus, inferior frontal gyrus, medial prefrontal cortex, superior temporal gyrus, inferior parietal lobule, caudate, the left insula, the right thalamus, and the left amygdala were activated. However, in the ironic sentence condition minus the literal sentence condition, we observed higher activation in the right medial prefrontal cortex (BA 10), the right precentral (BA 6), and the left superior temporal sulcus (BA 21). Our results suggest that irony comprehension is strongly related to mentalizing processes and that activation in these regions might be affected by higher-order cognitive operations.

Introduction. The frequency of different morphological types and extrasulcal (visible) surface area of the cingulate gyms, were measured and analyzed in order to obtain more precise data about morphology, right/left and sex differences in the human brain. Material and methods. The study included 42 brains (84 hemispheres) from persons of both sexes and of different age (26 males, 16 females, 20-65 years old), without neuropathological changes. After fixation in 10% formaline (3-4 weeks) and removal of meninges the brains were photographed under standard conditions by digital camera. Following determination of morphological type, regions of interest of cingulate gyrus were determined in stereotactic system system of coordinates and the extrasulcal surface was measured by digital AutoCAD planimetry. Results and discussion. Three basic morphological types of cingulate gyrus were found: the continuous type (34.5%), segmented type (35.7%) and double paralel type (29.8%). There was no statistically significant difference in the frequency of morphological types related to the side (right/left) or sex (p>0.05). The area of extrasulcal cortex of cingulate gyrus was statistically significantly (p

Physical agents such as non-ionizing continuous-wave 2.45GHz radiation may cause damage that alters cellular homeostasis and may trigger activation of the genes that encode heat shock proteins (HSP). We used Enzyme-Linked ImmunoSorbent Assay (ELISA) and immunohistochemistry to analyze the changes in levels of HSP-90 and its distribution in the brain of Sprague-Dawley rats, ninety minutes and twenty-four hours after acute (30min) continuous exposure to 2.45GHz radiation in a the Gigahertz Transverse Electromagnetic (GTEM cell). In addition, we studied further indicators of neuronal insult: dark neurons, chromatin condensation and nucleus fragmentation, which were observed under optical conventional or fluorescence microscopy after DAPI staining. The cellular distribution of protein HSP-90 in the brain increased with each corresponding SAR (0.034 ± 3.10-3, 0.069 ± 5.10-3, 0.27 ± 21.10-3 W/kg), in hypothalamic nuclei, limbic cortex and somatosensorial cortex after exposure to the radiation. At twenty-four hours post-irradiation, levels of HSP-90 protein remained high in all hypothalamic nuclei for all SARs, and in the parietal cortex, except the limbic system, HSP-90 levels were lower than in non-irradiated rats, almost half the levels in rats exposed to the highest power radiation. Non-apoptotic cellular nuclei and a some dark neurons were found ninety minutes and twenty-four hours after maximal SAR exposure. The results suggest that acute exposure to electromagnetic fields triggered an imbalance in anatomical HSP- 90 levels but the anti-apoptotic mechanism is probably sufficient to compensate the non-ionizing stimulus. Further studies are required to determine the regional effects of chronic electromagnetic pollution on heat shock proteins and their involvement in neurological processes and neuronal damage.

Accumulating evidence suggest a life-long impact of disease related mechanisms on brain structure in schizophrenia which may be modified by antipsychotic treatment. The aim of the present study was to investigate in a large sample of patients with schizophrenia the effect of illness duration and antipsychotic treatment on brain structure. Seventy-one schizophrenic patients and 79 age and gender matched healthy participants underwent brain magnetic resonance imaging (MRI). All images were processed with voxel based morphometry, using SPM5. Compared to healthy participants, patients showed decrements in gray matter volume in the left medial and left inferior frontal gyrus. In addition, duration of illness was negatively associated with gray matter volume in prefrontal regions bilaterally, in the temporal pole on the left and the caudal superior temporal gyrus on the right. Cumulative exposure to antipsychotics correlated positively with gray matter volumes in the cingulate gyrus for typical agents and in the thalamus for atypical drugs. These findings (a) indicate that structural abnormalities in prefrontal and temporal cortices in schizophrenia are progressive and, (b) suggest that antipsychotic medication has a significant impact on brain morphology.

Neurophysiological, biochemical, and anatomical evidence implicates glutamatergic mechanisms in epileptic seizures. Until recently, however, longitudinal characterization of in vivo glutamate dynamics was not possible. Here, we present data using in vivo magnetic resonance spectroscopy (MRS) optimized for the detection of glutamate to identify changes that evolve following kainic acid (KA)-induced status epilepticus. Wild-type male Wistar rats underwent whole brain MR imaging and single voxel MRS on a clinical 3T scanner equipped with a high-strength insert gradient coil. Scanning took place before and then 3 days, 28 – 32 days, and 42 – 50 days after induction of status epilepticus. Analyses compared 5 seizure (Sz), 5 no-seizure (NoSz; received KA but did not exhibit seizures), and 6 control (Con) animals. This longitudinal study demonstrated reduced glutamate levels in vivo in the dorsal hippocampus 3 days and 1 month following status epilepticus in Sz animals compared with Con animals. Additionally, previous results were replicated: in the Sz group, computed T2 was higher in the ventral hippocampus and limbic cortex 3 days after seizure activity compared with baseline but resolved in both regions at the 1 month scan, suggesting a transient edema. Three days following seizure activity, N-acetylaspartate (NAA) declined and lactate increased in the dorsal hippocampus of the Sz group compared with the Con and NoSz group; both metabolites approached baseline levels by the third scan. Taken together, these results support the conclusion that seizure activity following KA infusion causes loss of glutamatergic neurons.

International audience; Objective To investigate brain changes in both basal and cataplectic conditions in awake patients with narcolepsy-cataplexy.;Background Recent insights in pathophysiology have demonstrated that narcolepsy-cataplexy is caused by early loss of hypothalamus hypocretin neurons. However, the neurophysiological mechanisms underlying sleepiness and the dramatic cataplexy reaction to positive emotion remain unclear.;Methods Twenty-one patients with narcolepsy-cataplexy and 21 age- and sex-matched controls were included. Diagnosis of narcolepsy was fully confirmed by polysomnography, HLA DQB1*0602 and CSF hypocretin levels (n=9). Seven patients were free of all drugs, and 14 were treated with psychostimulant and/or anticataplectic drugs. (18)-F-fluorodeoxy glucose positron emission tomography procedures were performed at baseline in all subjects and during cataplexy attacks (n=2).;Results The authors found significant hypermetabolism in narcolepsy-cataplexy in fully awake condition in the limbic cortex specifically in the anterior and mid cingulate cortex, in the right cuneus and lingual gyrus. In contrast, no hypometabolism was found. Hypermetabolism was detected in the cerebellum and pre-postcentral gyri in treated compared with untreated patients. During cataplectic attacks, cerebral metabolism significantly increased in the bilateral pre-postcentral gyri, primary somatosensory cortex, with a marked decrease in the hypothalamus.;Conclusion Hypermetabolism was found in the executive network in narcolepsy at baseline in fully awake condition. Wake state assessment during scanning appears critical to avoid results showing altered functional neurocircuitry secondary to sleepiness and not to the underlying neurological disorder per se. Finally, cataplexy attacks were characterised by a hypometabolism in the hypothalamus associated with wide bilateral brain area hypermetabolisms.

Several neuropsychological and neuroimaging studies have been performed to clarify the neural bases of implicit learning, but the question of which brain regions are involved in different forms of implicit learning, including goal-directed learning and habit learning, has not yet been resolved. The present study sought to clarify the mechanisms of goal-directed implicit learning by examining the sugar production factory (SPF) task in conjunction with functional magnetic resonance imaging (fMRI). Several brain regions were identified that contribute to learning in the SPF task. Significant learning-related decreases in brain activity were found in the right inferior parietal lobule (IPL), left superior frontal gyrus, right medial frontal gyrus, cerebellar vermis, and left inferior frontal gyrus, while significant learning-related increases in activity were observed in the right inferior frontal gyrus, left precenteral gyrus and, left precuneus. Among these regions, we speculate that the IPL and medial frontal gyrus may specifically be involved in the early stage of goal-directed implicit learning. We also attempted to investigate the role of the striatum, which has a significant role in habit learning, during learning of the SPF task. The results of ROI analysis showed no learning-related change in the activity of the striatum. Although some of the observed learning-related activations in this study have also been previously reported in neuroimaging studies of habit learning, the possibility that specific brain regions involved in goal-direct implicit learning cannot be excluded.

Recent anatomo-clinical correlation studies have extended to the superior temporal gyrus, the right hemisphere lesion sites associated with the left unilateral spatial neglect, in addition to the traditional posterior-inferior-parietal localization of the responsible lesion (supramarginal gyrus, at the temporo-parietal junction). The study aimed at teasing apart, by means of repetitive transcranial magnetic stimulation (rTMS), the contribution of the inferior parietal lobule (angular gyrus versus supramarginal gyrus) and of the superior temporal gyrus of the right hemisphere, in making judgments about the mid-point of a horizontal line, a widely used task for detecting and investigating spatial neglect. rTMS trains at 25 Hz frequency were delivered over the inferior parietal lobule (angular gyrus and supramarginal gyrus), the superior temporal gyrus and the anterior parietal lobe of the right hemisphere, in 10 neurologically unimpaired participants, performing a line bisection judgment task. rTMS of the inferior parietal lobule at the level of the supramarginal gyrus brought about a rightward error in the bisection judgment, ipsilateral to the side of the rTMS, with stimulation over the other sites being ineffective. The neural correlates of computing the mid-point of a horizontal segment include the right supramarginal gyrus in the inferior parietal lobule and do not extend to the angular gyrus and the superior temporal gyrus. These rTMS data in unimpaired subjects constrain the evidence from lesion studies in brain-damaged patients, emphasizing the major role of a subset of relevant regions.

Object Knowledge of the cranium projections of the gyral structures is essential to reduce the surgical complications and to perform minimally invasive interventions in daily neurosurgical practice. Thus, in this study the authors aimed to provide detailed information on cranial projections of the eloquent cortical areas. Methods Ten formalin-fixed adult human skulls were obtained. Using sutures and craniometrical points, the crania were divided into 8 windows: superior frontal, inferior frontal, superior parietal, inferior parietal, sphenoidal, temporal, superior occipital, and inferior occipital. The projections of the precentral gyrus, postcentral gyrus, inferior frontal gyrus, superior temporal gyrus, transverse temporal gyri, Heschl gyrus, genu and splenium of the corpus callosum, supramarginal gyrus, angular gyrus, calcarine sulcus, and sylvian fissure to cranial vault were evaluated. Results Three-fourths of the precentral gyrus and postcentral gyrus were in the superior parietal window. The inferior frontal gyrus extended to the inferior parietal window in 80%. The 3 important parts of this gyrus were located below the superior temporal line in all hemispheres. The orbital and triangular parts were in the inferior frontal window, and the opercular part was in the inferior parietal window. The superior temporal gyrus was usually located in the inferior parietal and temporal windows, whereas the supramarginal gyrus and angular gyrus were usually located in the superior and inferior parietal windows. The farthest anterior point of the Heschl gyrus was usually located in the inferior parietal window. The mean positions of arachnoid granulations were measured as 3.9 ± 0.39 cm anterior and 7.3 ± 0.51 cm posterior to the bregma. Conclusions Given that recognition of the gyral patterns underlying the craniotomies is not always easy, awareness of the coordinates and projections of certain gyri according to the craniometric points may considerably contribute to surgical interventions.

Aims: In this study, the appearance and distribution of neurofibrillary tangles (NFT) in diffuse neurofibrillary tangles with calcification (DNTC) were investigated neuropathologically in order to elucidate the detailed distribution pattern in this disease. Methods: The distribution of NFT in six cases neuropathologically diagnosed as DNTC (two men and four women) was studied using Gallyas–Braak silver stain. The age at death ranged from 56 to 73, with an average of 63.5 ± 7.5 years. Results: NFT were seen throughout the cerebral cortex, and were especially marked in the temporal and limbic cortices. The distribution pattern of NFT in the limbic lobe was similar to that in Alzheimer's disease as reported in the previous studies. In the temporal lobe, more NFT were distributed in the anterior than in the posterior area, which was confirmed in all six cases. The temporal pole showed the highest density of NFT including ghost tangles. Conclusions: The diffuse appearance of NFT in the cerebral cortex with the highest severity in the temporal pole was found to be a neuropathological characteristic of DNTC.

Although the common marmoset has become a model for the study of several neurological conditions that affect the frontal lobe, knowledge of the boundaries of the areas located in the orbital and medial frontal regions has remained incomplete. Here we examined histological sections stained for myelin, Nissl substance, and cytochrome oxidase, allowing identification of likely homologues of most of the architectural fields defined in Old World monkeys. Ventrally, we identified three granular fields at or near the frontal pole (area 10, and the medial and lateral subregions of area 11), and two granular fields along the lateral margin of the orbitofrontal cortex (medial and orbital subdivisions of area 12). More caudal and medially, dysgranular and agranular cortices included four subdivisions of area 13 as well as rostral and caudal subdivisions of area 14 (at the ventromedial convexity). The ventral frontotemporal transition encompassed at least two subdivisions of agranular insular cortex, as well as the likely homologues of the gustatory cortices. Most of the medial surface was encompassed by area 10 (which projected a caudomedial finger-like extension toward the subgenual cortex), together with a relatively large dysgranular area 32 and an agranular area 25 (in subgenual cortex). Finally, the caudal limit of the medial frontal cortex included two fields of agranular cingulate cortex (areas 24a and 24b). These findings enhance our understanding of the architectural organization of the marmoset frontal cortex and highlight a highly conserved basic organization across simian primates, allowing the informed interpretation of experimental neurological studies.

The impact of juvenile stress exposure on astrocyte plasticity was assessed in the precocious rodent Octodon degus. Astrocytes expressing S100ss and glial fibrillary acidic protein (GFAP) were quantified in the limbic medial prefrontal cortex (mPFC), including the anterior cingulate (ACd), precentral medial (PrCm), infra- (IL) and prelimbic (PL) cortex and in the "non-limbic" somatosensory cortex (SSC). At the age of 21 days we compared (i) controls (C), (ii) stressed animals (SSR: separation stress/short reunion), which were exposed to 6 h separation from the family, followed by 1 h reunion with the family and (iii) stressed animals (SER: separation stress/extended reunion), which were stressed like group SSR but exposed to 48 h reunion. The observed glia response was already measurable 7 h after the onset of the stress exposure. Compared to controls SER and SSR animals showed elevated densities of S100ss-IR astrocytes in layers II/III and V-VI of the ACd, IL and PrCm, whereas no significant group differences were observed in the PL and SSC. The SSR group showed significantly decreased density of GFAP-immunoreactive astrocytes in all mPFC subregions. Only in the ACd the stress-induced changes in glia density were still evident after 48 h reunion with the family. Compared to controls, the length of GFAP-IR processes and the number of ramification points were significantly reduced in all mPFC subregions and in the SSC of the SSR group. In the SSC the stress-evoked changes in GFAP-glia density were opposite compared to the changes seen in the medial prefrontal cortical subregions, whereas the changes in GFAP-labeled processes were comparable to those observed in the mPFC. In summary, these results demonstrate that a single stress episode induces rapid and quite complex region- and cell-specific changes in glial cells, reflected by an upregulation of cytoplasmic (S100ss) and downregulation of cytoskeletal (GFAP) glial protein.

Background Functional brain imaging studies have consistently demonstrated abnormalities in regional cerebral glucose metabolism in the prefrontal cortex in patients with mood disorders (MD). These studies, however, have not clarified the differential characteristics of glucose metabolism between depressed and euthymic states, or between bipolar mood disorder (BP) and unipolar mood disorder (UP). Methods We used [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET) to evaluate the differences in glucose metabolism at resting state. We compared 30 depressed and 17 euthymic female patients with mood disorders with age-, IQ-, and socioeconomically matched 20 healthy controls (HCs). Then, BP and UP patients were separately analyzed. The PET data were objectively analyzed by statistical parametric mapping (SPM). Results Compared with HCs, the depressed MD patients showed significantly lower glucose metabolism in the bilateral frontal gyri, left cingulate gyrus, bilateral temporal gyri, right insula, bilateral inferior parietal lobules, and right occipital gyrus. In contrast, the euthymic MD patients demonstrated fewer areas with significant reduction. When the depressed BP patients were separately compared with HCs, the glucose metabolism was found to be significantly lower in the bilateral frontal gyri, right cingulate gyrus, and bilateral inferior parietal lobules. Meanwhile, the depressed UP patients showed a significantly lower metabolism in the bilateral frontal gyri, left cingulate gyrus, bilateral temporal gyri, bilateral insulae, bilateral inferior parietal lobules, and right occipital gyrus. Conclusions The results of this study provide evidence of persistent hypometabolism in depressed MD patients, particularly in the frontal gyrus. Although the conclusions are limited in the cross-sectional study, these findings suggest that abnormalities in the right frontal gyrus, left temporal gyrus, and left cingulate gyrus tend to normalize as the depression symptoms improve, although those in the left frontal gyrus, right cingulate gyrus, and right temporal gyrus persist. This study also elucidated the cerebral hypofunction specific to each BP and UP. BP patients showed a decrease in glucose metabolism in the right anterior cingulate and UP patients did in the right temporal gyrus, right insula, and left posterior cingulate. This study clarified the differences between subtypes.

Biological motion, the movement of the human body presented by a small number of point lights, activates among other regions lining the posterior superior temporal sulcus (pSTS) and gyrus (pSTG) and of the fusiform gyrus. In previous studies with foveal stimuli the activity in the pSTS/pSTG was often confined to the right hemisphere and bilateral in fusiform gyrus. We presented biological motion stimuli in peripheral vision and measured the BOLD responses with functional MRI to test whether the right dominance in pSTS/pSTG also occurred with peripheral stimuli. We found activation exclusively in the right pSTG for both visual hemifields. In the fusiform gyrus activation was found in both hemispheres and for peripheral stimuli strongest for contralateral stimulation. However, in both fusiform gyri leftward-facing stimuli activated different subfields than rightward-facing stimuli, indicating a clustering of the selectivity for the orientation of the human body form. No such clustering was observed in the pSTG. The results indicate for the fusiform gyrus an organization with respect to the view orientation of the stimulus.

Object It has been hypothesized that specific brain regions involved in face naming may exist in the brain. To spare these areas and to gain a better understanding of their organization, the authors studied patients who underwent surgery by using direct electrical stimulation mapping for brain tumors, and they compared an object-naming task to a famous face–naming task. Methods Fifty-six patients with brain tumors (39 and 17 in the left and right hemispheres, respectively) and with no significant preoperative overall language deficit were prospectively studied over a 2-year period. Four patients who had a partially selective famous face anomia and 2 with prosopagnosia were not included in the final analysis. Results Face-naming interferences were exclusively localized in small cortical areas (< 1 cm2). Among 35 patients whose dominant left hemisphere was studied, 26 face-naming specific areas (that is, sites of interference in face naming only and not in object naming) were found. These face naming–specific sites were significantly detected in 2 regions: in the left frontal areas of the superior, middle, and inferior frontal gyri (p < 0.001) and in the anterior part of the superior and middle temporal gyri (p < 0.01). Variable patterns of interference were observed (speech arrest, anomia, phonemic, or semantic paraphasia) probably related to the different stages in famous face processing. Only 4 famous face–naming interferences were found in the right hemisphere. Conclusions Relative anatomical segregation of naming categories within language areas was detected. This study showed that famous face naming was preferentially processed in the left frontal and anterior temporal gyri. The authors think it is necessary to adapt naming tasks in neurosurgical patients to the brain region studied.

Several behavioral and neuroimaging studies have indicated that both right and left cortical structures and a few subcortical ones are involved in processing affective prosody. Recent investigations have shown that the mirror neuron system plays a crucial role in several higher-level functions such as empathy, theory of mind, language, etc., but no studies so far link the mirror neuron system with affective prosody. In this paper is a speculation that the mirror neuron system, which serves as a common neural substrate for different higher-level functions, may play a significant role in processing affective prosody via its connections with the limbic lobe. Actual research must apply electrophysiological and neuroimaging techniques to assess whether the mirror neuron systems underly affective prosody in humans.

– This article deals with the efferent connections of the hippocampal region, and considers the functional implications of these projections. The hippocampus receives indirect sensory information from many structures in the brain. Most of these afferents terminate in the superficial layers (I-III) of the entorhinal area. From cells in layers II and III of entorhinal area projections arise which terminate in hippocampus and fascia dentata, the perforant paths. Internal hippocampal projections constitute a unidirectional system of connections which project back to the deep layers (IV-VI) of the entorhinal area. The efferents from these layers may be divided into cortically terminating efferents, which originate from layer IV, and subcortically terminating efferents, which originate from layers V and VI. The cortically terminating projections end in regions of association cortex, and in limbic cortex. The subcortical projections terminate in the caudate, the putamen, and the accumbens nucleus. A hippocampal influence on these subcortical structures may seem surprising, but is logical when one takes into consideration reports on the functional associations between the striatum and the hippocampus. The findings suggest that the role of the hippocampus may be to gather input from all sensory modalities, to assign priorities continuously between these inputs, and as a result, to modify behavior via its influence on subcortical motor centres.

In the human brain information about bodies and faces is processed in specialized cortical regions named EBA and FBA (extrastriate and fusiform body area) and OFA and FFA (occipital and fusiform face area), respectively. Here we investigate with functional magnetic resonance imaging (fMRI) the cortical areas responsible for the identification of individual bodies and the distinction between 'self' and 'others'. To this end we presented subjects with images of unfamiliar and familiar bodies and their own body. We identified separate coactivation networks for body-detection (processing body related information), body-identification (processing of information relating to individual bodies) and self-identification (distinction of self from others). Body detection involves the EBA in both hemispheres, and in the right hemisphere: the FBA and areas in the IPL (inferior parietal lobe). Body identification involves areas in the inferior frontal gyrus (IFG) of both hemispheres and in the right hemisphere areas in the medial frontal gyrus (MFG), in the cingulate gyrus (CG), in the central (CS) and the post-central sulcus (PCS), in the inferior parietal lobe (IPL) and the FBA. When the recognition of one's own body is contrasted to the identification of familiar bodies, differential activation is observed in areas of the inferior parietal lobe (IPL) and inferior parietal sulcus (IPS) of the right hemisphere, and in the posterior orbital gyrus (pOrbG) and in the lateral occipital gyrus (LOG) of the left hemisphere. Thus, identification of individual bodies and self-other distinction involve in addition to the classical occipito-parietal network a parieto-frontal network. Interestingly, the EBA shows no differential activation for distinctions between familiar or unfamiliar bodies or recognition of one's own body.

Voice production involves precise, coordinated movements of the intrinsic and extrinsic laryngeal musculature. A component of normal voice production is the modification of pitch. The underlying neural networks associated with these complex processes remains poorly characterized. However, several investigators are currently utilizing neuroimaging techniques to more clearly delineate these networks associated with phonation. The current study sought to identify the central cortical mechanism(s) associated with pitch variation during voice production using event-related functional MRI (fMRI). A single-trial design was employed consisting of three voice production tasks (low, comfortable, and high pitch) to contrast brain activity during the generation of varying frequencies. For whole brain analysis, volumes of activation within regions activated during each task were measured. Bilateral activations were shown in the cerebellum, superior temporal gyrus, insula, precentral gyrus, postcentral gyrus, inferior parietal lobe, and post-cingulate gyrus. In the left hemisphere, activations in the medial and middle frontal gyri were also observed. Regions active during high pitch production when compared to comfortable pitch were evident in the bilateral cerebellum, left inferior frontal gyrus, left cingulate gyrus, and left posterior cingulate. During low pitch generation, activations were present in the inferior frontal gyrus, insula, putamen, and cingulate gyrus in the left hemisphere. The inferior frontal gyrus in the right hemisphere produced greater activity than the area of the left hemisphere during high and low pitch generation. These results suggest that a single-trial design is sensitive enough to begin to delineate a widespread network of activations in both hemispheres associated with vocal pitch variation.

発話開始困難と中断が目立つ非流暢性失語症を呈したが，その他の言語症状は軽微であった症例について，その非流暢性の原因を検討した。症例は83 歳，右利きの女性。左中前頭回後部から中心前回前部にかけての脳梗塞を発症，第１病日はごく軽度の失構音があり，非流暢性が著明であった。語列挙や文の構成障害がなく，発話衝動は保たれ，失構音は速やかに改善したにも関わらず，自由発話における発話開始困難と中断が遷延した。非流暢性発話の二大要因である失構音と言語発動性の低下を欠き，本症例における非流暢性の原因として，前頭葉由来の思考障害，思考の言語化の障害，選択肢が多い場合の語句の選択の困難さが考えられた。本症例の病巣は，多くの典型的 Broca 失語の病巣に含まれることから，本症例の非流暢性発話の原因が，典型的 Broca 失語の非流暢性発話の一因となっていることが予想される。

Previous research has implicated the medial prefrontal cortex (mPFC) in the control of classically conditioned autonomic and somatomotor responses. In eyeblink (EB) classical conditioning prefrontal involvement appears to be limited to paradigms that are more difficult to learn, in that acquisition is slower. These include trace conditioning and discrimination/reversal. Some of this research suggests that the participation of mPFC in classical EB conditioning is related to the intensity or type of unconditioned stimulus (US) employed. In the present two experiments we thus studied the effects of manipulation of periorbital shock intensity as the US in Experiment 1 and in Experiment 2 the intensity of a corneal airpuff as the US on Pavlovian trace EB conditioning. The results indicate that there are optimal intensities of both airpuff and periorbital shock as the US in the demonstration of mPFC control of trace classical EB conditioning.

Biased recruitment and sample selection may cause variability in neuroimaging studies. Epidemiologically principled population-based magnetic resonance imaging (MRI) studies of schizophrenia are very rare. We gathered structural MRI data on 154 subjects from the Northern Finland 1966 Birth Cohort, aged 33-35 (100 controls, 54 schizophrenia patients). Regional differences in density of gray matter, white matter, and cerebrospinal fluid (CSF) were identified between groups using nonparametric statistical analysis, and the relationship of the regional differences to duration of illness was explored. Gray matter reductions were found bilaterally in the cerebellum, thalamus, basal ganglia, middle frontal gyrus, inferior frontal gyrus, precentral gyrus, insula, superior temporal gyrus, fusiform gyrus, parahippocampal gyrus, cuneus, and lingual gyrus; in the left posterior cingulate, superior frontal gyrus, transverse temporal gyrus, and precuneus; and in the right postcentral gyrus. Gray matter excesses were observed bilaterally in the basal ganglia, anterior cingulate, and medial orbitofrontal cortices. There were white matter deficits in an extensive network including inter- and intrahemispheric tracts bilaterally in the frontal, temporal, parietal, and occipital lobes, subcortical structures, cerebellum, and brain stem. CSF excesses were found bilaterally in the lateral ventricles, third ventricle, interhemispheric, and left Sylvian fissure. We replicated the previous findings of structural brain abnormalities in schizophrenia on a general population level. Gray and white matter deficits were associated with duration of illness suggesting either that developmental brain deficits relate to an earlier age of onset or that brain abnormalities in schizophrenia are progressive in nature.

We describe a 9-year-old boy who presented with abnormal development in language and social interaction. He also showed evidence of stereotyped behaviour, thus fulfilling all the criteria for an ICD-10 diagnosis of autism. This was associated with multiple pituitary deficiency. No case of autism associated with hypopituitarism has hitherto been reported. The authors discuss the evidence for linking the two conditions as opposed to accepting them as coincidental. In some studies of autism, anatomical and imaging studies have provided evidence of pathology in the limbic lobe. This lobe plays an essential role in the modification and expression of emotional reactions. Together with other areas, the limbic system sends outputs from the hypothalamus and from there to the pituitary. Our case illustrates a possible link between emotional expression and hypopituitarism.

The objective of the present study was to determine differences in neural networks between expert and novice archers during an archery pre-performance routine period (PPR). The experiment was conducted with eight world-class competitor or Olympic medalist archers and eight novices. In the experiment, the task was to shoot (by clicking a mouse with the right hand) if an archery target appeared on an LCD embedded in an functional magnetic resonance imaging (fMRI) scanner. The resultant fMRI data showed that when the experts were aiming, the occipital gyrus and temporal gyrus were activated, but when the novices were aiming, the frontal area was mainly activated. In addition, the anterior cingulate and posterior cingulate gyrus of the limbic lobe were also activated in the expert and novice groups, respectively. Our results demonstrated that expert and novice archers differed in levels of brain activation during the PPR period of a simulated archery task.

Fatal familial insomnia, a human prion disease, Morvan's chorea, an autoimmune limbic encephalopathy, and delirium tremens, the well-known alcohol (or benzodiazepine [BDZ]) withdrawal syndrome, share a clinical phenotype largely consisting in an inability to sleep associated with motor and autonomic activation. Agrypnia excitata is the term which aptly defines this clinical condition, whose pathogenetic mechanism consists in an intralimbic disconnection releasing the hypothalamus and brainstem reticular formation from corticolimbic inhibitory control. Severance of cortical–subcortical limbic structures is due to visceral thalamus degeneration in fatal familial insomnia, and may depend on autoantibodies blocking voltage-gated potassium channels within the limbic system in Morvan's chorea, and the sudden changes in gabaergic synapses down-regulated by chronic alcohol abuse within the limbic system in delirium tremens. On the basis of these findings, we suggest that a neuronal network, extending from the medulla to the limbic cortex, controls the sleep–wake cycle, operating in an integrated fashion following a caudorostral organization.

The brain amygdala complex (AC) participates in awide spectrum of motivational and emotional behav-ioral responses, which are accompanied by changes inthe visceral and endocrine systems [1]. AC projectionsto the anterior limbic cortex are an important pathwayof AC effects on the integrative brain functionsinvolved in visceral regulation [2–4].Numerous neuroanatomical data indicate that ACprojections run from the parvicellular region of the ACbasal nucleus to deeper layers of the prelimbic andinfralimbic cortices [5]. However, the neurophysiolog-ical mechanisms of the amygdalocortical effects medi-ated by this connections remain unclear., To date, theinhibitory and excitatory AC effects on cells of the ante-rior limbic cortex have been described in a few reports[3, 6–8], though nothing is known about the neurotrans-mitters of these processes.At the same time, nitric oxide (NO) is generallyknown to be one of the most important neurotransmit-ters and/or neuromodulators in the central nervous sys-tem [9, 10]. NO is synthesized by some cortical cells[11, 12] and plays an important role in the regulation ofcortical processes; in particular, it modulates the releaseof γ-aminobutyric acid and acetylcholine [10, 13].The nitroergic activity of cortical neurons may bealso involved in the mechanisms underlying the ACeffects on the anterior limbic cortex. Nitroergic activitymodulation may change the level of neuronal excitabil-ity in the prelimbic and infralimbic regions and, hence,the sensitivity of these regions to the regulatory influ-ences of other brain structures, including the ACnucleus.We verified this hypothesis in a series of histochem-ical and neurophysiological experiments performed onWistar male rats weighing 250–360 g; the animals wereanesthetized with urethane (1.5 g/kg body weight;intraperitoneal administration). In response to electricalstimulation of the parvicellular part of the AC basalnucleus, the NO-synthase activity in various regions ofthe anterior limbic cortex was studied histochemically(detection of intracellular nicotinamide dinucleotidephosphate diaphorase (NADP-d). In neurophysiologi-cal experiments, the effects of the same AC nucleusstimulation on the neuronal activity of the anterior lim-bic cortex were studied before and after the administra-tion of 7-nitroindasol, a blocker of the neuronalNO-synthase, into the left lateral brain ventricle. Two groups of animals, each containing four rats(the control one without stimulation and the group ofelectrically stimulated animals) were used in his-tochemical studies. The surgical preparation was thesame in both groups. The parvicellular part of the basalAC nucleus was subjected to a monopolar electricalstimulation in a region with the following coordinates:3.3 mm caudal of bregma, 5.0 mm lateral of the medianline, and about 7.0 mm away from the dorsal brain sur-face; tungsten electrodes in varnish insulation wereused (tip diameter, 50–60 µm; resistance, 80–100 kΩ).Three series of 0.5-ms rectangular pulses were used(current, 30–50 µA). The pulse frequency in a serieswas 50 pulses per second, the series length was 10 s,and the interval between series was 20 s.On completion of the stimulation, the animals weretranscardially perfused with 4% paraformaldehydesolution; 24 h later, 30-µm frontal sections across theanterior limbic cortex were made using a freezingmicrotome. The sections were treated histochemicallyto detect NADP-d according to a modified method ofScherer-Singler et al. [14]. NADP-d-positive neuronswere located, and their number and optical densitywere determined on the cortical sections using animage-analyzing device, which was connected with apersonal computer; the program packages Video TestMaster 4.0 and Image Tool were used. The neuronaloptical density was expressed in arbitrary units(arb. un.) within a range from 0 (a white object) to 1.55(a black object).Neurophysiological experiments were performed on34 rats. In this experimental series, the parvicellularpart of the AC basal nucleus was stimulated by solitaryrectangular pulses with the same parameters. The neu-ronal responses from the anterior limbic cortex were

A comparative study of mmunoreactivity with respect to c-Fos protein in the motor (zones М1 and М2), medial prefrontal (PrL and IL), and cingular (Cg1 and Cg2) cortices allowed us to find significant differences between the intensities of expression of gene c-fos in these cortical regions in control rats (group 1) and animals trained to perform catching of food globules by the forelimb (i.e., realizing an operant food-procuring reflex, group 2). The density of distribution of Fos-immunoreactive (Fos-ir) neurons in rats of group 2 in motor and limbic cortical zones at +2.2 to +0.2 levels rostrally from the bregma were significantly lower than in control rats (Р Cg2 > М1 > М2 > > PrL. As is supposed, NADPH-d-r neurons (i.e., cells generating NO) are involved in the control of regional blood flow in the studied cortical regions.

Earlier studies have suggested abnormal brain volumes in autism, but inconsistencies exist. Using voxel-based morphometry, we compared global and regional brain volumes in 17 high-functioning autistic children with 15 matched controls. We identified significant reduction in left white matter volume and white/gray matter ratio in autism. Regional brain volume reductions were detected for right anterior cingulate, left superior parietal lobule white matter volumes, and right parahippocampal gyrus gray matter volume, whereas enlargements in bilateral supramarginal gyrus, right postcentral gyrus, right medial frontal gyrus, and right posterior lobe of cerebellum gray matter in autism. Our findings showed global and regional brain volumes abnormality in high-functioning autism.

This study aimed to clarify chronological sequences of the appearances of sulci and gyri on the medial cerebral surface and its relation to the regional development of the cerebrum in cynomolgus monkeys. The lengths of cingulate and calcarine sulci were measured, and the ratios of these lengths to fronto-occipital length were estimated as indices of the size of the "frontoparietal" and "occipital" regions, respectively. The relative length of cingulate sulcus showed a biphasic increase: a slow phase from EDs 100 to 110, and a rapid phase from EDs 110 to 130. The gyri in the "frontoparietal region" were convoluted in the limbic cortex during the initial slow phase and in the neocortical region during the rapid phase. The relative length of calcarine sulcus lineally increased between EDs 90 and 130, and the gyri in the "occipital region" generated in a dorso-ventral manner: the gyrus convolutions occurred first in the "phylogenetically older" striate and dorsal extrastriate cortices, and then in the "phylogenetically newer" ventral extrastriate cortex. The results suggest that the chronological order of appearance of sulci and gyri is closely associated with the order of phylogenetical development of the cerebral cortex. The present study provides a standard reference for the development of cerebral sulci and gyri of cynomolgus monkeys together with our previous study (Fukunishi et al. Anat Embryol 211:757-764, 2006).

Purpose: Detection of cortical abnormalities in relapsing-remitting multiple sclerosis (RRMS) remains elusive. Structural magnetic resonance imaging (MRI) measures of cortical integrity are limited, although functional techniques such as pseudo-continuous arterial spin labeling (pCASL) show promise as a surrogate marker of disease severity. We sought to determine the utility of pCASL to assess cortical cerebral blood flow (CBF) in RRMS patients with (RRMS-I) and without (RRMS-NI) cognitive impairment. Methods: A total of 19 age-matched healthy controls and 39 RRMS patients were prospectively recruited. Cognition was assessed using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery. Cortical CBF was compared between groups using a mass univariate voxel-based morphometric analysis accounting for demographic and structural variable covariates. Results: Cognitive impairment was present in 51.3% of patients. Significant CBF reduction was present in the RRMS-I compared to other groups in left frontal and right superior frontal cortex. Compared to healthy controls, RRMS-I displayed reduced CBF in the frontal, limbic, parietal and temporal cortex, and putamen/thalamus. RRMS-I demonstrated reduced left superior frontal lobe cortical CBF compared to RRMS-NI. No significant cortical CBF differences were present between healthy controls and RRMS-NI. Conclusion: Significant cortical CBF reduction occurs in RRMS-I compared to healthy controls and RRMS-NI in anatomically significant regions after controlling for structural and demographic differences.

Objective To examine gender differences and similarities in the psychophysical and brain responses to acupuncture at GB34, a point that is frequently used to treat motor function issues in Traditional Chinese Medicine. Methods Functional MRI (fMRI) was used to measure brain activation in response to acupuncture at GB34 (on the right) in 19 healthy participants (9 male, 10 female). De qi sensations were rated to measure their psychophysical responses. Results Overall de qi scores did not differ by gender, although females reported greater intensity of aching (p=0.04). Acupuncture activated the hippocampus, thalamus, globus pallidus, caudate body, claustrum, cingulate gyrus, and culmen in males, and the middle and inferior frontal gyrus, precuneus, postcentral gyrus, inferior parietal lobule, superior temporal gyrus, caudate body, insula, fusiform gyrus, cingulate gyrus, amygdala, and parahippocampal gyrus in females. The middle/medial frontal gyrus, middle temporal gyrus, thalamus, globus pallidus, caudate body, uvula, and cerebellar tonsil were activated when data from all subjects were combined. Relative to males, females exhibited greater brain activation in the right-sided postcentral gyrus, precentral gyrus, precuneus, postcentral gyrus, inferior parietal lobule, declive, middle occipital gyrus and parahippocampal gyrus. Conclusions The neural effects of GB34 acupuncture might differ between males and females because different brain structures were modulated in response to acupuncture. This potential gender effect should be taken into account in future clinical research. We also revealed that the caudate body was activated by GB34 acupuncture in both males and females and may represent a major target of GB34 acupuncture. Trial Registration Number KMC IRB 0861-06.

Catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) genes have been found to interactively influence working memory (WM) as well as brain activation during WM tasks. However, whether the two genes have interactive effects on resting-state activities of the brain and whether these spontaneous activations correlate with WM are still unknown. This study included behavioral data from WM tasks and genetic data (COMT rs4680 and BDNF Val66Met) from 417 healthy Chinese adults and resting-state fMRI data from 298 of them. Significant interactive effects of BDNF and COMT were found for WM performance as well as for resting-state regional homogeneity (ReHo) in WM-related brain areas, including the left medial frontal gyrus (lMeFG), left superior frontal gyrus (lSFG), right superior and medial frontal gyrus (rSMFG), right medial orbitofrontal gyrus (rMOFG), right middle frontal gyrus (rMFG), precuneus, bilateral superior temporal gyrus, left superior occipital gyrus, right middle occipital gyrus, and right inferior parietal lobule. Simple effects analyses showed that compared to other genotypes, subjects with COMT-VV/BDNF-VV had higher WM and lower ReHo in all five frontal brain areas. The results supported the hypothesis that COMT and BDNF polymorphisms influence WM performance and spontaneous brain activity (i.e., ReHo).

Major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) are two of the most common and disabling psychiatric disorders. Although clinical nosological systems place them in separate diagnostic categories, there is a high rate of comorbidity between the two and they are treated with similar pharmacological agents (although typically requiring different doses). In this chapter, we will review the current neuroimaging evidence to explain the pathophysiology of these two conditions, highlighting the overlapping and differing regions and circuits involved.

The frontal cortex is a heterogeneous region of the cerebral hemisphere consisting of many different cytoarchitectonic areas. The ventrolateral frontal region in the language-dominant hemisphere has been shown to be directly involved in certain aspects of language production. This frontal region includes three motor areas on the precentral gyrus (areas 4, 6VC, and 6VR) that are succeeded anteriorly by area 44 on the pars opercularis and area 45 on the pars triangularis of the inferior frontal gyrus. Areas 44 and 45 are traditionally considered to constitute Broca’s region: the anterior language production cortical zone. The posterior part of the dorsomedial frontal region, including the supplementary motor area, contributes to verbal fluency. Although damage to the various dorsolateral prefrontal cortical areas does not impair language comprehension or production, they do participate in verbal processing by virtue of their role in higher control processes that regulate attention and working memory.

It is suggested that the dentate gyrus and hilar region in the hippocampus perform memory selection and that the selectivity of the gating of memory by this circuit is modulated by the norepinephrine–glutamate loop described by Mather et al.

The rostromedial tegmental nucleus (RMTg) interconnects extensively with the basal ganglia. Major input to the RMTg comes from the ventral pallidum–lateral preoptic–lateral hypothalamic continuum, which receives cortico-basal ganglia output from the entire cortical limbic lobe. Neocortical input to the RMTg involves a basal ganglia–lateral habenula–RMTg pathway. Other input to the RMTg comes from the lateral deep layers of the contralateral superior colliculus, midbrain extrapyramidal area, and several other rostral brainstem structures, of which nearly all are targeted by basal ganglia outputs and project to motor effector sites. RMTg projects densely to aforementioned brainstem structures (from which it receives inputs) and to the midbrain dopamine complex, which, via the basal ganglia, profoundly modulates locomotion and affect. The reported capacity of the RMTg to detect and influence behavioral responses to aversive, threatening, and disappointing circumstances likely involves its substantial interconnections with basal ganglia.

Brain functions during the resting state have attracted considerable attention in the past several years. However, little has been known about spontaneous activity in the sensory cortices in the task-free state. This study used functional magnetic resonance imaging (fMRI) to investigate the existence of spontaneous activity in the primary visual areas (PVA) of normal-sighted subjects and to explore the physiological implications of such activity. Our results revealed that we were able to detect spontaneous activity, which was nonrandom in that it was distinctly clustered both temporally and spatially in the PVA of each subject. In addition, the neural network associated with the PVA-related spontaneous activity included the visual association areas, the precuneus, the precentral/postcentral gyrus, the middle frontal gyrus, the fusiform gyrus, the inferior/middle temporal gyrus, and the parahippocampal gyrus. After considering the functions of these regions, we speculated that the PVA-related spontaneous activity may be associated with memory-related mental imagery and/or visual memory consolidation processes. These findings confirm the presence of spontaneous activity in the PVA and related brain areas. This confirmation supports the perspective that brain is a system intrinsically operating on its own, and sensory information interacts with rather than determines the operation of the system.

Sensation-seeking is a human personality trait associated with a greater propensity to use psychoactive substances. A rat model showing face validity of this human trait has been developed. The model is based on the variety of behavioral responses that rats exhibit in a novel and inescapable environment, with some animals (high-responders, HR) being highly active, and others (low-responders, LR) showing less exploration. More active rats (HR) also show increased drug-taking and decreased anxiety-like behavior. There is evidence that response to novelty may rely on differential 5-HT-mediated neurotransmission. This research focuses on the recently discovered 5-HT6 and 5-HT7 receptors which share affinity for neuroleptic drugs and hallucinogens. To date, emerging evidence suggests that 5-HT6 and 5-HT7 may be involved in cognition and mood regulation, respectively. To further our knowledge of their behavioral attributes, we compared patterns of gene expression for these receptors in the brains of HR and LR rats. As a control, gene expression for the 5-HT3 receptor was investigated because its contribution to anxiety and addiction is only weakly demonstrated. Transcript levels for 5-HT6 in the olfactory tubercle inversely correlated with the level of locomotion in a novel environment. Phenotype differences in mRNA signal for 5-HT6 showed a complex pattern in the dentate gyrus. LR rats were statistically higher in the most anterior region of the dentate gyrus, while HR rats were higher in median areas of the dentate gyrus. Levels of 5-HT7 transcript in HR rats were significantly lower than LR rats in pivotal areas for information trafficking, such as thalamo-cortical projection areas and dorsal hippocampus. By contrast, phenotype differences in 5-HT3 expression were not found in areas of the limbic cortex and mesolimbic system. Taken together, these results provide new insight into the potential contribution of 5-HT to novelty-seeking behavior and associated behaviors such as substance abuse.

This study compared the patterns of brain activation elicited by single-digit addition and multiplication problems. 20 Chinese undergraduates were asked to verify whether arithmetic equations were true or false during functional magnetic resonance imaging. Results showed that both addition and multiplication were supported by a broad neural system that involved regions within SMA, precentral gyrus, intraparietal sulcus, occipital gyri, superior temporal gyrus, and middle frontal gyrus, as well as some subcortical structures. Nevertheless, addition problems elicited more activation in the intraparietal sulcus and middle occipital gyri at the right hemisphere, and superior occipital gyri at both hemispheres, whereas multiplication had more activation in precentral gyrus, supplementary motor areas, and posterior and anterior superior temporal gyrus at the left hemisphere. This pattern of dissociated activation supports our hypothesis that addition has greater reliance on visuospatial processing and multiplication on verbal processing.

To understand neural reorganization of response regulation after stroke, a 54-year-old woman with a chronic left thalamic stroke performed a task requiring decisions about the directionality of an arrow during cerebral functional magnetic resonance imaging. Her performance was compared to 13 matched healthy control subjects. Her behavioral responses were slower but as accurate. Bilateral frontal activations were observed in the right medial frontal gyrus (BA 9), left superior frontal gyrus (BA 45), and left frontal rectus gyrus (BA 11). Activation in the right medial frontal gyrus, along with activity in close proximity to the anterior cingulate cortex, was observed, which may reflect reorganization of activity after the loss of function of the anterior cingulate cortex.

The intranasal trigeminal system is involved in the perception of odors. To investigate the cerebral processing of sensory information from the trigeminal nerve in detail we studied subjects with and without olfactory function using functional magnetic resonance imaging. A normosmic group (n=12) was compared with a group of anosmic subjects (n=11). For trigeminal stimulation gaseous CO(2) was used. Following right-sided stimulation with CO(2) controls exhibited a stronger right-sided cerebral activation than anosmic subjects. Stronger activation was found in controls compared to anosmic subjects for the right prefrontal cortex, the right somatosensory cortex (SI), and the left parietal insula. In contrast, relatively higher activation was found in anosmic subjects for the left supplementary motor area in the frontal lobe, the right superior and middle temporal lobe, the left parahippocampal gyrus in the limbic lobe, and the sub-lobar region of the left putamen and right insula which was mostly due to a decreased BOLD signal of controls in these areas. Additional conjunction analysis revealed that activated areas common to the two groups were the cerebellum and the right premotor frontal cortex. These data suggest that the processing of the trigeminally mediated information is different in the presence or absence of an intact sense of smell, pointing towards the intimate connection between the two chemosensory systems.

Lobus limbicus is an anatomical basis for understanding the temporal epilepsy because it includes not only the focus of temporal lobe infection but of the frontal lobe as well. With it we can explain many of the phenomena accompanying epilepsy (hallucinations, the change of the effects, and so on). The goal of this assignment was to explore the asymmetry of amygdaloidal complex in the patients with complex partial attacks. The results show that the smallest number of patients with epilepsy have a symmetric (same size) amygdaloidal complex on the left side and the right. According to the asymmetry direction the difference in the number of patients with epilepsy is not statistically significant. Coefficient of asymmetry shows that the asymmetry on the left side is more frequent in men, while women have the same distribution on both sides. The greatest differences were found when considering the age factor. So, in all the three groups of evaluated data the differences in average age of patients with epilepsy according to total symm./asymm. were not statistically significant. But, the differences in average age depending on the direction of asymmetry were significant. Patients with longer amygdaloidal complex on the left side are significantly younger, both male and female (related to the axial slice, ant. - post. diameter). Thus, we propose the application of MRI technique in examining the asymmetry of the amygdaloidal complex that we used in this assignment as a template for future examinations in a sense of shedding light on the anatomical functions that underlie neuro-psychiatric dysfunctions.

Theoretical models for lexical access to visual objects have been based mainly on adult data. To investigate the developmental aspects of object recognition and lexical access in children, a large-scale functional MRI (fMRI) study was performed in 283 normal children ages 5−18 using a word–picture matching paradigm in which children would match an aurally presented noun to one of two pictures (line drawings). Using group Independent Component Analysis (ICA), six task-related components were detected, including (a) the posterior superior temporal gyrus bilaterally; (b) the fusiform, inferior temporal, and middle occipital gyri bilaterally; (c) the dorsal aspect of the inferior frontal gyrus bilaterally, the left precuneus, the left superior/middle temporal gyrus, and the anterior cingulate; (d) the right medial fusiform gyrus; (e) a left-lateralized component including the inferior/middle frontal, middle temporal, medial frontal, and angular gyri, as well as the thalamus and the posterior cingulate; and (f) the ventral/anterior aspect of the inferior frontal gyrus bilaterally. Increased activation associated with age was seen in the components (b) and (d) (ventral visual pathway) for object recognition, and (c) and (f) likely associated with semantic maintenance and response selection. Increased activation associated with task performance was seen in components (b) and (d) (ventral visual pathway) while decreased activation associated with task performance was seen in component (f) (ventral/anterior inferior frontal gyrus). The results corroborate the continued development of the ventral visual pathway throughout the developmental period.

Hippocampal structural plasticity induced by entorhinal cortex (EC) lesions has been studied extensively in the rat, but little comparable research has been conducted in primates. In the current study we assessed the long-term effects of bilateral aspiration lesions of the EC on multiple markers of circuit organization in the hippocampal dentate gyrus of young adult monkeys (Macaca fascicularis). Alternate histological sections were processed for the visualization of somatostatin and vesicular acetylcholine transporter (VAChT) immunoreactivity and acetylcholinesterase histochemistry (AChE). The markers revealed the distinct laminar organization of dentate gyrus circuitry for stereology-based morphometric quantification. Consistent with findings in rats, the volume of the somatostatin-immunopositive outer molecular layer (OML), innervated by projections from the EC, was decreased by 42% relative to control values. The inner molecular layer (IML) displayed a corresponding volumetric expansion in response to denervation of the OML as measured by AChE staining, but not when visualized for quantification by VAChT immunoreactivity. Nonetheless, stereological estimation revealed a 36% increase in the total length of VAChT-positive cholinergic fibers in the IML after EC damage, along with no change in the OML. Together, these findings suggest that despite substantial species differences in the organization of hippocampal circuitry, the capacity for reactive plasticity following EC damage, previously documented in rats, is at least partly conserved in the primate dentate gyrus. J. Comp. Neurol. 500:192–201, 2007. © 2007 Wiley-Liss, Inc.

Exposing pups of the rodent species Octodon degus to periodic separation stress during the first three postnatal weeks leads to behavioral alterations, which include reduced attention towards an emotional stimulus and motoric hyperactivity. These behavioral changes, which are reminiscent of symptoms of attention deficit hyperactivity disorder (ADHD), are paralleled by synaptic changes in the dorsal anterior cingulate cortex (ACd), a limbic cortex region, which plays a key role in the modulation of attentional and executive functions. ADHD is typically treated with methylphenidate (MP), a drug acting on the dopaminergic system. However, the effect of chronic MP-treatment on neuronal and synaptic maturation in the developing brain is unknown. Applying the Golgi-Cox stainining technique, we tested in which way chronic MP-treatment interferes with dendritic and synaptic development in the ACd and whether this treatment can restore the stress-induced changes of neuronal connectivity. We found that chronic treatment with 1 mg/kg MP recovers stress-induced changes of spine densities in the ACd. Furthermore, MP-treatment resulted in increased dendritic length and complexity in both, stressed as well as unstressed control animals. These results indicate that synaptic reorganization as well as dendritic growth in the prefrontal cortex continue into prepuberty and are modulated by MP-treatment. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007

Byline: V. RajMohan, E. Mohandas "The hypothalamus, the anterior thalamic nucleus, the cingulate gyrus, the hippocampus and their interconnections, constitute a harmonious mechanism which may elaborate the functions of central emotion as well as participate in the emotional expression." James Papez, 1937 The limbic system consists of the phylogenetically old limbic lobe and other subcortical structures and their connections. Although not empirically proven, the limbic system is a functional concept which may be employed to explain various brain functions.[sup] [1] History Paul Pierre Broca in 1878 spoke of ' le grand lobe limbique' or the great limbic lobe and applied the term "limbic" (from the Latin limbus for border) to the curved rim of the cortex which incudes the cingulate and the parahippocampal gyri. However, its putative role in emotion was elaborated by the American physician, James Papez in 1937 in the seminal paper titled 'A proposed mechanism of emotion'. This anatomical model is referred to as the Papez circuit.[sup] [2] Yakovlev in 1948 proposed Yakovlev's circuit in the control of emotion involving the orbitofrontal, insular and anterior temporal lobe cortex, the amygdala and the dorsomedial nucleus of thalamus.[sup] [3] In 1952, Paul D. MacLean coined the term "limbic system" to describe Broca's limbic lobe and related subcortical nuclei as the collective neural substrate for emotion.[sup] [1] MacLean was also instrumental in proposing and defining the Triune concept of the brain. MacLean's evolutionary "Triune brain theory" proposed that the human brain was in reality three brains in one: the R-complex (reptilian complex), the limbic system and the neocortex.[sup] [4] The concept of the limbic system has since been further expanded and developed by Nauta, Heimer and others. Components of the Limbic System There is no universal agreement on the total list of structures, which comprise the limbic system. The brain regions that constitute the limbic system are: *Limbic cortex i. Cingulate gyrus ii. Parahippocampal gyrus *Hippocampal formation i. The dentate gyrus ii. Hippocampus iii. Subicular Complex *Amygdala *Septal area *Hypothalamus These structures form a complex network for controlling emotion.[sup] [5] Limbic lobe The limbic lobe situated at the inferomedial aspect of the[sup] cerebral hemispheres, consists of two concentric gyri surrounding[sup] the corpus callosum. Broca proposed that the larger outer gyrus[sup] be named[sup] " limbic gyrus" and the smaller inner one "the intralimbic gyrus".[sup] The limbic gyrus (limbic lobe) consists of the[sup] isthmus of the cingulate gyrus, the parahippocampal gyrus (both of which are continuous via a bundle of white matter called "cingulum") and the subcallosal area.[sup] [6] The cingulate gyrus (Latin = Belt ridge) dorsal to the corpus callosum is heavily interconnected with the association areas of the cerebral cortex. The parahippocampal gyrus in the medial temporal lobe contains several distinct regions, the most important being the entorhinal cortex (ERC). The ERC funnels highly processed cortical information to the hippocampal formation and serves as its major output pathway.[sup] [5] The hippocampal formation Hippocampal formation in the temporal lobe has three distinct zones: *The dentate gyrus *The hippocampus proper *The subiculum Embryologically, the hippocampal formation is an extension of the medial edge of the temporal lobe. The entire hippocampal formation has a length of about 5 cm from its anterior end at the amygdala to its tapering posterior end near the splenium of the corpus callosum.[sup] [5] Dentate gyrus The dentate gyrus is composed of three layers: an outer acellular molecular layer, a granular middle layer and an inner polymorphic layer. …

When we evaluate an option, how is the neural representation of its value linked to information that identifies it, such as its position in space? We hypothesized that value information and identity cues are not bound together at a particular point but are represented together at the single unit level throughout the entirety of the choice process. We examined neuronal responses in two-option gambling tasks with lateralized and asynchronous presentation of offers in five reward regions: orbitofrontal cortex (OFC, area 13), ventromedial prefrontal cortex (vmPFC, area 14), ventral striatum (VS), dorsal anterior cingulate cortex (dACC), and subgenual anterior cingulate cortex (sgACC, area 25). Neuronal responses in all areas are sensitive to the positions of both offers and of choices. This selectivity is strongest in reward-sensitive neurons, indicating that it is not a property of a specialized subpopulation of cells. We did not find consistent contralateral or any other organization to these responses, indicating that they may be difficult to detect with aggregate measures like neuroimaging or studies of lesion effects. These results suggest that value coding is wed to factors that identify the object throughout the reward system and suggest a possible solution to the binding problem raised by abstract value encoding schemes.

The perception of the faces of parents is different from that of other faces. Mother's face perception is associated with childbearing and parenting and has specific cognitive processing properties. Yet, the underlying mechanism remains unknown. We investigated the neural network that is involved in the perception of parent's face based upon parental face selective tasks that were completed by 23 normal adults. Resting state functional magnetic resonance imaging (fMRI) and a task block design with fixation cross sign control fMRI were used. The faces activated the right inferior frontal gyrus, the left and right middle frontal gyri, and the left and right inferior parietal lobule. In addition, the parental faces task resulted in more activation than the control tasks in the left and right anterior cingulate, left middle (superior) temporal gyrus, right and left inferior frontal gyrus. The anterior cingulate cortex (ACC) and the inferior parietal lobe (IPL) are central nodes of the brain network, while the parental face perception network includes the anterior cingulate cortex and superior temporal gyrus (ACC-STG)/parahippocampal network as well as the inferior frontal and inferior parietal lobule (IFG-IPL) network. The network of father's face perception involves the left inferior parietal lobule and left middle frontal gyrus/right middle frontal gyrus/right inferior frontal gyrus, while mother's face perception involves the right inferior parietal lobe and frontal network (MFG.L/IFG.R). The experiments showed that the ACC-STG/parahippocampal network and IFG-IPL network are neural networks used in parental face perception, and the ACC and IPL are central nodes in the network. The neural pathway of parental face perception is similar to the perception of a stranger's face, as both include the STG, but is different in that the perception of the stranger's face involves a connected STG and IPL as a specific neural pathway.

Although generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders in older adults, very little is known about the neurobiology of worry, the hallmark symptom of GAD in adults over the age of 60. This study investigated the neurobiology and neural circuitry of worry in older GAD patients and controls.Twenty older GAD patients and 16 age-matched controls (mean age = 67.88) were compared on clinical measures and neural activity during worry using functional magnetic resonance imaging.As expected, worry elicited activation in frontal regions, amygdala, and insula within the GAD group, with a similar but less prominent frontal pattern was observed in controls. Effective connectivity analyses revealed a positive directional circuit in the GAD group extending from ventromedial through dorsolateral prefrontal cortices, converging on the amygdala. A less complex circuit was observed in controls with only dorsolateral prefrontal regions converging on the amygdala; however, a separate circuit passing through the orbitofrontal cortex converged on the insula.Results elucidate a different neurobiology of pathological versus normal worry in later life. A limited resource model is implicated wherein worry in GAD competes for the same neural resources (e.g. prefrontal cortical areas) that are involved in the adaptive regulation of emotion through cognitive and behavioral strategies.

Focal temporal lobe seizures often cause impaired cortical function and loss of consciousness. Recent work suggests that the mechanism for depressed cortical function during focal seizures may depend on decreased subcortical cholinergic arousal, which leads to a sleep-like state of cortical slow-wave activity. To test this hypothesis, we sought to directly activate subcortical cholinergic neurons during focal limbic seizures to determine the effects on cortical function. Here we used an optogenetic approach to selectively stimulate cholinergic brainstem neurons in the pedunculopontine tegmental nucleus during focal limbic seizures induced in a lightly anesthetized rat model. We found an increase in cortical gamma activity and a decrease in delta activity in response to cholinergic stimulation. These findings support the mechanistic role of reduced subcortical cholinergic arousal in causing cortical dysfunction during seizures. Through further work, electrical or optogenetic stimulation of subcortical arousal networks may ultimately lead to new treatments aimed at preventing cortical dysfunction during seizures.