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Recent functional brain imaging studies with positron emission tomography (PET) suggest a preference of the right hemisphere, especially the anterior cingulate cortex (ACC), in affective processing of the clinical pain syndromes. We have investigated the central processing of cluster headache (CH) attacks provoked by sublingual nitroglycerin (NTG). In the cerebrum, provoked CH activated the ACC and the temporopolar region of the right hemisphere in addition to other regions. The regions activated in the ACC (Brodmann area (BA) 24 and 32) are involved in affective/cognitive processing of pain and willed attention. Our study discloses the preferential role of the right hemisphere in attributing emotional valence and attention to the suffering of pain. The findings support the theory of a right hemispheric specialisation in the mediation of withdrawal-related negative affect. The divergence of the distributed central processing between provoked cluster headache attack and experimentally induced acute pain indicates different central mechanisms for different types of pain.

This study was undertaken to explore whether the neural substrates demonstrated in brain imaging studies on experimentally induced pain are involved in the perception of chronic neuropathic pain. We investigated the cerebral representation of chronic lateralised ongoing pain in patients with painful mononeuropathy (PMN, i.e., pain in the distribution of a nerve, neuralgia) with positron emission tomography (PET), using regional cerebral blood flow (rCBF) as an index for neuronal activity. Eight patients (29-53 years) with PMN in the lower extremity (4 in the right, 4 in the left) were recruited. Paired comparisons of rCBF were made between the patient's habitual pain (HP) state and the pain alleviated (PA) state following a successful regional nerve block (RNB) with lidocaine. The ongoing neuropathic pain resulted in activation of bilateral anterior insula, posterior parietal, lateral inferior prefrontal, and posterior cingulate cortices as well as the posterior sector of the right anterior cingulate cortex (ACC), Brodmann area (BA) 24, regardless of the side of PMN. In addition, a reduction in rCBF was noted in the contralateral posterior thalamus. No significant change of rCBF was detected in the somatosensory areas, i.e., SI and SII. The cerebral activation pattern, while addressing the differences between the HP and PA states, emphasises the affective-motivational dimension in chronic ongoing neuropathic pain. The striking preferential activation of the right ACC (BA 24), regardless of the side of the PMN, not only confirms that the ACC participates in the sensorial/affectional aspect of the pain experience but also suggests a possible right hemispheric lateralisation of the ACC for affective processing in chronic ongoing neuropathic pain. Our data suggests that the brain employs different central mechanisms for chronic neuropathic pain and experimentally induced acute pain, respectively.

The contingent negative variation (CNV) is a brain potential generated during delay periods that has been proposed to measure prefrontal cortex (PFCx) activity. The CNV was recorded in neurological patients with PFCx damage centered in Brodmann areas 9, 44, 45, and 46 in a classical auditory S1-S2 paradigm employing a 3 sec interstimulus interval. Subjects pressed a button upon detection of an acoustically cued imperative tone (S2, 1000 Hz, GO). Responses were withheld if the warning tone (S1, 1500 Hz in GO trials) was lower in frequency (500 Hz, NOGO). The early phase of the CNV (500-700 msec after S1) was not reduced in patients with PFCx damage. PFCx lesions reduced the later phase of the CNV beginning about 1000 msec prior to S2. Reductions were maximal over PFCx sites but extended to posterior scalp electrodes over the lesioned hemisphere. The results are consistent with a late CNV generator in dorsolateral PFCx that also modulates generation of the potential in posterior regions of the ipsilateral hemisphere. The CNV findings coupled with behavioral evidence of impaired preparatory processes in these patients support the role of PFCx in sustaining distributed neural activity during delay periods.

1. Differences in the distribution of relative regional cerebral blood flow during motor imagery and execution of a joy-stick movement were investigated in six healthy volunteers with the use of positron emission tomography (PET). Both tasks were compared with a common baseline condition, motor preparation, and with each other. Data were analyzed for individual subjects and for the group, and areas of significant flow differences were related to anatomy by magnetic resonance imaging (MRI). 2. Imagining movements activated a number of frontal and parietal regions: medial and lateral premotor areas, anterior cingulate areas, ventral opercular premotor areas, and parts of superior and inferior parietal areas were all activated bilaterally when compared with preparation to move. 3. Execution of movements compared with imagining movements led to additional activations of the left primary sensorimotor cortex and adjacent areas: dorsal parts of the medial and lateral premotor cortex; adjacent cingulate areas; and rostral parts of the left superior parietal cortex. 4. Functionally distinct rostral and caudal parts of the posterior supplementary motor area (operationally defined as the SMA behind the coronal plane at the level of the anterior commissure) were identified. In the group, the rostral part of posterior SMA was activated by imagining movements, and a more caudoventral part was additionally activated during their execution. A similar dissociation was observed in the cingulate areas. Individual subjects showed that the precise site of these activations varied with the individual anatomy; however, a constant pattern of preferential activation within separate but adjacent gyri of the left hemisphere was preserved. 5. Functionally distinct regions were also observed in the parietal lobe: the caudal part of the superior parietal cortex [medial Brodmann area (BA) 7] was activated by imagining movements compared with preparing to execute them, whereas the more rostral parts of the superior parietal lobe (BA 5), mainly on the left, were additionally activated by execution of the movements. 6. Within the operculum, three functionally distinct areas were observed: rostrally, prefrontal areas (BA 44 and 45) were more active during imagined than executed movements; a ventral premotor area (BA 6) was activated during both imagined and executed movements; and more caudally in the parietal lobe, an area was found that was mainly activated by execution presumably SII. 7. These data suggest that imagined movements can be viewed as a special form of "motor behavior' that, when compared with preparing to move, activate areas associated heretofore with selection of actions and multisensory integration.(ABSTRACT TRUNCATED AT 400 WORDS)

Four percent of 88 Alzheimer’s patients seen in 1992–93 at the Memory Disorders and Alzheimer’s Disease Center at Loyola University of Chicago had as the presenting symptom difficulty in processing visual information. Complex visual disturbances have been described in Alzheimer’s disease (AD), including constructional and visuoperceptual disorientation, spatial agnosia, facial identification problems, Balint’s syndrome, and impairment of contrast sensitivity functions (Adelstein et al. 1992, Mendez et al. 1992, Rizzo et al. 1992, Hof and Bouras 1991, Cronin-Golomb et al. 1991, Mendez et al. 1990 a,b, Flicker et al. 1990). This widespread visual dysfunction may reflect known pathological changes in the primary visual pathways or in the association cortex, or both. Pathological changes have been described in the optic nerve (Hinton et al. 1986, Sadun 1989), the primary and the association visual cortices (Lewis et al. 1987, Armstrong et al. 1990, Bell and Ball 1990, Levine et al. 1992). Trick et al (1989) and Katz et al (1989) have reported changes in the pattern electroretinograms suggesting that there is a quantifiable retinal ganglion cell dysfunction in Alzheimer’s disease. However, Katz et al. (1989) also found that pattern VEPs and flash VEPs had normal P100 responses but had a delayed second positive component suggesting a dysfunction of visual association cortex. In a prospective study (Mendez et al., 1990) found that all 30 patients studied had some disturbances in figure analysis, and 57% of these patients had some form of visual agnosia. These authors concluded that complex visual disturbances are more frequent than previously realized.

To identify cortical regions activated during saccades and visual fixation, regional cerebral blood flow (rCBF) was measured in eight healthy subjects using C15O2 PET during the performance of three tasks: (i) central fixation; (ii) reflexive saccades to random targets; (iii) remembered saccades to locations of recent target appearance. Significant rCBF increases were identified using analysis of covariance and the t statistic (P < 0.001). Compared with central fixation there was activation of striate and extra-striate cortex, posterior parietal cortex (PPC) and frontal eye fields (FEF) during both reflexive and remembered saccades. During remembered saccades there was additional activation of supplementary motor area (SMA), insula, cingulate, thalamus, midbrain, cerebellum and right superior temporal gyrus (Brodmann's area 22). Compared with the individual saccadic tasks, central fixation activated extensive regions of ventromedial (areas 10, 11 and 32) and anterolateral (areas 8, 9, 10, 45 and 46) prefrontal cortex, and foveal visual cortex. We conclude that FEF and PPC are associated with the generation of both reflexive and remembered saccades, with SMA additionally involved during remembered saccades. Sustained voluntary fixation is mediated by prefrontal cortex.

Purpose: We devised a new computer-aided diagnosis method to segregate dementia using one estimated index (Total Z score) derived from the Brodmann area (BA) sensitivity map on the stereotaxic brain atlas. The purpose of this study is to investigate its accuracy to differentiate patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI) from normal adults (NL). Methods: We studied 101 adults (NL: 40, AD: 37, MCI: 24) who underwent 18 FDG positron emission tomography (PET) measurement. We divided NL and AD groups into two categories: a training group with (Category A) and a test group without (Category B) clinical information. In Category A, we estimated sensitivity by comparing the standard uptake value per BA (SUVR) between NL and AD groups. Then, we calculated a summated index (Total Z score) by utilizing the sensitivitydistribution maps and each BA z-score to segregate AD patterns. To confirm the validity of this method, we examined the accuracy in Category B. Finally, we applied this method to MCI patients. Results: In Category A, we found that the sensitivity and specificity of differentiation between NL and AD were all 100%. In Category B, those were 100% and 95%, respectively. Furthermore, we found this method attained 88% to differentiate ADconverters from non-converters in MCI group. Conclusions: The present automated computer-aided evaluation method based on a single estimated index provided good accuracy for differential diagnosis of AD and MCI. This good differentiation power suggests its usefulness not only for dementia diagnosis but also in a longitudinal study.

Context The hypothesis of a serotonin (5-hydroxytryptamine [5-HT]) dysfunction in obsessive-compulsive disorder (OCD) stems largely from the clinical efficacy of 5-HT reuptake inhibitors. Serotonergic abnormalities in the unmedicated symptomatic state, however, remain to be fully characterized. Objective To investigate brain regional 5-HT synthesis, as indexed by positron emission tomography and theα-[ 11 C]methyl-L-tryptophan trapping constant (K*), in treatment-free adults meeting criteria for OCD. Design Between-group comparison. Setting Department of Psychiatry and Montreal Neurological Institute, McGill University, and Department of Psychology, McGill University Health Centre, Quebec, Canada. Participants Twenty-one medication-free patients with OCD (15 men with a mean [SD] age of 33.2 [9.3] years and 6 women with a mean [SD] age of 35.8 [7.1] years) and 21 healthy controls matched for age and sex (15 men with a mean [SD] age of 32.9 [10.1] years and 6 women with a mean [SD] age of 36.5.5 [8.6] years). Main Outcome Measure Theα-[ 11 C]methyl-L-tryptophan brain trapping constant K*, which was analyzed with Statistical Parametric Mapping (SPM8) and with proportional normalization (extent threshold of 100 voxels with a peak threshold of P ≤ .005). Results Compared with healthy controls, the patients with OCD exhibited significantly greaterα-[ 11 C]methyl-L-tryptophan trapping in the right hippocampus and left temporal gyrus (Brodmann area 20). In the larger subsample of all men, these same differences were also evident, as well as higher K* values in the caudate nucleus. Individual differences in symptom severity correlated positively with K* values sampled from the caudate and temporal lobe of the patients with OCD, respectively. There were no regions where the patients exhibited abnormally low K* values. Volumetric analyses found no morphometric alterations that would account for the group differences. Conclusion The results support previous reports of greater striatal and temporal lobe activity in patients with OCD than in healthy controls and suggest that these disturbances include a serotonergic component. Previously reported glucose metabolic disturbances in OCD involving the orbitofrontal and cingulate cortices, in comparison, might reflect postsynaptic changes in the serotonergic system.

Behavioral and brain functions 7, 15 (2011). doi:10.1186/1744-9081-7-15, Published by BioMed Central, London

Neuropsychological assessment of 16 clinically non-demented patients with amyotrophic lateral sclerosis (ALS) and 16 age-matched controls revealed significantly (P < 0.05) impaired verbal fluency and picture recall in the ALS patients. On the basis of their verbal fluency scores, two subgroups of the ALS patients (five high, five low scores) and a different group of five age-matched controls then underwent positron emission tomographic (PET) measurement of regional cerebral blood flow (rCBF). Scans were performed in the resting state and while subjects performed stereotyped or freely selected movements of a joystick with their right hand. The pattern of cerebral activation associated with self-generated activity was determined by comparing the profile of rCBF during freely selected and stereotyped joystick movements. Statistical parametric mapping was used to determine significant differences in rCBF between the groups at rest and during activation. Regional cerebral blood flow at rest was significantly (P < 0.01) reduced in the anterior cingulate cortex of both ALS subgroups in comparison with controls. The profile of cortical and subcortical activation during performance of freely selected joystick movements relative to stereotyped movements was abnormal in ALS patients: (i) ALS patients with a normal fluency score showed significantly (P < 0.01) attenuated rCBF responses in comparison with controls in the left medial prefrontal cortex (Brodmann area 10) and the right and left parahippocampal gyri; (ii) ALS patients with impaired verbal fluency showed significantly (P < 0.01) attenuated rCBF responses in comparison with controls in the right and left medial prefrontal cortex (areas 9 and 10), the rostral aspects of the right anterior cingulate cortex (areas 24 and 32), the right parahippocampal gyrus and the anterior thalamic nuclear complex; (iii) ALS patients with impaired verbal fluency showed significantly (P < 0.01) attenuated rCBF responses in comparison with patients with normal verbal fluency in the right parahippocampal gyrus, the anterior thalamic nuclear complex and the rostral anterior cingulate cortex (area 24). Regional cerebral blood flow at rest in the right parahippocampal gyrus of ALS patients was significantly correlated with verbal fluency score (P = 0.01) and picture recall score (P = 0.01). Activation of the anterior thalamic nuclear complex in ALS patients was also significantly correlated with verbal fluency score (P = 0.001) and picture recall score (P = 0.01). The results show that abnormalities of function are present in regions along a limbo-thalamo-cortical pathway in some ALS patients during performance of a self-generated motor task.(ABSTRACT TRUNCATED AT 400 WORDS)

The relationships of the "primary" cytoarchitectonic neocortical fields, 17, 41, 3b, and 4 (Brodmann areas), to salient topographic landmarks have been reconstructed from serial histological sections in 20 human cerebral hemispheres (10 brains). Each of these architectonic fields is found to bear a characteristic relationship to a set of enframing anatomic landmarks, in particular, gyri, fissures, and sulci, that can be readily defined by MRI. Two classes of variability were found characteristic, at least to some extent, of each of the fields. Class 1 variability--variability that is not predictable from visible landmarks--was typical of the polar and for the cuneal and lingual extracalcarine distributions of field 17 and the distribution of field 4 upon the paracentral lobule. Class 2 variability--variability that is closely predictable from visible landmarks--is seen in the marked interindividual or interhemispheric variation in size or shape of a field and was found to be prominent for all four fields. Because of the prominence of class 2 variability, direct reference to the landmarks that frame these fields may be expected to be a more reliable basis for functional mapping than reference to a template or stereotactic coordinate-based system of reference to a standard or idealized brain.

A primary goal of investigations into the organization of human cerebral cortex is to determine the functional specificity of architectonic regions. This includes the correlation of neurobehavioral deficits with neuropathological data for clinical diagnosis and treatment, and the identification of active brain regions using functional neural imaging techniques, such as positron emission tomography, electroencephalographic and magnetoencephalographic (EEG and MEG) source localization algorithms, and direct cortical stimulation. Currently, the architectonic classification of a cortical region identified by these methods is inferred from the comparison of its cerebral topographic position to cytoarchitectonic brain atlases. However, substantial intersubject variability in the position of cytoarchitectonic regions with respect to cerebral topographic landmarks may lead to errors in this procedure. An alternative method is presented here, which uses magnetic resonance (MR) imaging to identify myeloarchitectonic regions of isocortex directly by estimating the relative concentration of myelin within cortical laminae. This high-resolution MR protocol is used to identify striate cortex (Brodmann's area 17) and extrastriate cortex in vivo. Correspondence of MR signal intensity with myeloarchitectonic data from a postmortem brain confirms this identification. As MR imaging technology improves, this noninvasive method has the potential to identify and discriminate among at least 50 cortical regions in the living human brain.

Clinical and neuropathological studies have shown evidence of subgroups and heterogeneity in the presentation of Alzheimer’s disease (AD). To quantify the degenerating process, we have been able to set up a reliable experimental protocol based upon an immunoblot analysis of pathological tau proteins, referred to as tau 55, 64 and 69, which are known to be early and reliable markers of AD. These markers allowed us to map easily the distribution of the neurofibrillary degeneration. The mapping was performed in the 46 Brodmann areas of the brains from five Alzheimer patients with similar duration of the disease. In all cases, the detection of tau 55, 64 and 69 was positive in all areas except in primary visual cortex (area 17) for two patients. The quantities of abnormal tau were especially strong in temporal neocortical and limbic areas and were higher in associative cortex than in primary sensory cortex. Using this quantitative approach, we observed three factors of heterogeneity: 1. occipital and frontal lobes were sometimes less affected by the degenerating process while limbic and temporal lobes were constantly and strongly affected, showing a heterogenous pattern along the rostrocaudal axis; 2. the comparison of the amounts of abnormal tau proteins found in the temporal area (AB21) of 10 AD patients with different ages of onset was also undertaken. Generally we observed a decrease of the quantity of abnormal tau in late onset cases, but the brain of one very old AD patient contained huge amounts of abnormal tau proteins in all neocortical areas; 3. despite a very short duration of illness (18 months), one patient exhibited a general and large amount of abnormal tau proteins expressed in all cortical areas and in the neostriatum. We conclude that our biochemical approach is very convenient to apprehend the extent and the intensity of the degenerating process. This approach demonstrates the heterogeneity of AD.

Context Disturbances in neural systems that mediate voluntary self-regulatory processes may contribute to bulimia nervosa (BN) by releasing feeding behaviors from regulatory control. Objective To study the functional activity in neural circuits that subserve self-regulatory control in women with BN. Design We compared functional magnetic resonance imaging blood oxygenation level–dependent responses in patients with BN with healthy controls during performance of the Simon Spatial Incompatibility task. Setting University research institute. Participants Forty women: 20 patients with BN and 20 healthy control participants. Main Outcome Measure We used general linear modeling of Simon Spatial Incompatibility task–related activations to compare groups on their patterns of brain activation associated with the successful or unsuccessful engagement of self-regulatory control. Results Patients with BN responded more impulsively and made more errors on the task than did healthy controls; patients with the most severe symptoms made the most errors. During correct responding on incongruent trials, patients failed to activate frontostriatal circuits to the same degree as healthy controls in the left inferolateral prefrontal cortex (Brodmann area [BA] 45), bilateral inferior frontal gyrus (BA 44), lenticular and caudate nuclei, and anterior cingulate cortex (BA 24/32). Patients activated the dorsal anterior cingulate cortex (BA 32) more when making errors than when responding correctly. In contrast, healthy participants activated the anterior cingulate cortex more during correct than incorrect responses, and they activated the striatum more when responding incorrectly, likely reflecting an automatic response tendency that, in the absence of concomitant anterior cingulate cortex activity, produced incorrect responses. Conclusions Self-regulatory processes are impaired in women with BN, likely because of their failure to engage frontostriatal circuits appropriately. These findings enhance our understanding of the pathogenesis of BN by pointing to functional abnormalities within a neural system that subserves self-regulatory control, which may contribute to binge eating and other impulsive behaviors in women with BN.

Our laboratory has measured mRNA pool sizes in neocortex afflicted with Alzheimer’s disease (AD). We have observed a repression of gene expression in the temporal and parietal regions compared to age-matched control neocortex. These changes in messenger RNA pool size closely parallel the observed alterations in local cerebral metabolic rates for glucose (LCMR-g), as detected by positron emission tomography (PET). For example, deficits in both gene transcription and glucose metabolism appear to be the greatest in AD-affected superior temporal neocortex (Brodmann area 22) but are less apparent in the primary visual cortex (Brodmann area 17) or in the cerebellum. The unresolved question is whether changes in gene expression are the cause or effect of altered glucose metabolism. However, the non-random reductions in the pool size for certain neocortical mRNAs argue in favour of altered gene expression as the primary event.

The materials presented in this chapter are intended to provide the reader with an introductory knowledge of the anatomy of the human nervous system. Such a knowledge is necessary prior to discussion of the signs, symptoms and neurological mechanisms underlying the various neurogenic speech-language disorders in later chapters. Where necessary, more detailed information regarding the anatomy of specific brain structures important for speech-language function is provided in subsequent relevant chapters.

Background and AimsAutism (MIM#209850) is a complex neurodevelopmental affection that is largely genetic psychiatric disorder. Several genes have been found associated with autism but their expression levels and neuropathological effects remain unknown in autistic brain.MethodsWe compare the level of expression of autism candidate genes in post-mortem brain region samples between controls and patients. We studied Brodmann area (BA) 46 and the granule cells of the cerebellum lobule 6, for which neuropathological findings and functional abnormalities have been reported in autism.ResultsDifferent levels of transcription for SLC25A12/AGC1, EN2 and Nr-CAM genes are observed in the cortex and granule cells. Difference of expression are observed between patients and controls. We focused on SLC25A12 for which polymorphisms have been associated to autism in various studies. SLC25A12 encodes the mitochondrial aspartate/glutamate carrier and its function is requested to produce energy in neurons. By hybridation in situ, we analysed the expression pattern of SLC25A12 in human development and we studied the effects of SLC25A12 over-expression on mouse embryonic cortical neurons.ConclusionsConvergent evidence suggest that level of expression of candidate genes may be involved in autism pathophysiology by modifying neuronal networks and molecular plasticity in specific brain subregions at both pre- and postnatal stages.SponsorAutism Tissue Program and Federation pour la Recherche sur le Cerveau

We investigated whether findings from pretreatment low-resolution electromagnetic tomography (LORETA) predicted response to drug treatment in patients with obsessive-compulsive disorder (OCD). The 3D intra-cerebral distribution of neuronal electrical activity from the scalp-recorded potential distribution of 17 drug-free patients with OCD was assessed with LORETA. They were treated with antidepressants in the maximum tolerated doses for at least 12 wk. Individuals were considered to be treatment responders if they displayed a reduction of at least 35% on the initial YBOCS scores and had a final CGI score of 1 or 2. The SPM-99 t test for independent samples was employed to compare, voxel-by-voxel, the brain electrical activities of responders (n = 10) and non-responders (n = 7). Responders exhibited significantly lower activities in beta band in the rostral anterior cingulate [Brodmann's area (BA) 24 and 32] (p = 0.002) and the medial frontal gyrus (BA 10) (p = 0.002), suggesting that a distinctive pattern of activity within the medial surface of the frontal lobe predicts therapeutic response in OCD.

Brain atrophy has been reported in a number of MR studies of aging leg ‘) *’ Importantly, age-related alterations in regional volumes . have been correlated with performance on neuropsychological and experimental cognitive tasks ‘3, 41. Thus, changes in cortical morphology may have clinical significance. Similarly, understanding patterns of regional degeneration in the brain may aid in distinguishing between normal aging and preclinical dementia. Volumetric studies have provided valuable information on changes in the brain associated with aging “I. Still, few studies have examined changes over the entire cortex due to the labor-intensive nature of such measurements. We employed measurements of cortical thickness “’ based on accurate, automated reconstmctions of the brain from MR scans 16. ‘I allowing visualization of change across the complete cortical surface. Methods Structural MR scans were obtained from younger (YP; n = 19; mean age = 23.6, 18-31; 9MllOF) and older participants (OP; n = 10; mean age = 75.9.66-89; 3M/7F). All participants were nondemented (CDR = 0). YP were recruited from the Washington University community. OP were recruited through the Washington University Alzheimer’s Disease Center. OP were excluded if they had a history of neurologic, psychiatric, or medical illness that could contribute to dementia. Two to four MP-RAGE scans were averaged per participant (Siemens 1.5-T Vision System, resolution 1 X 1 X 1.25 mm, TR = 9.7ms, TE = 4ms, FA = lo”, TI = 20ms, TD = 500ms). Thickness measurements were obtained by reconstructing representations of the gray/white matter boundary and the cortical surface and then calculating the minimal distance between those two surfaces for each point on the gray/white matter boundary “I. Thickness maps were averaged across participants using a spherical morph to align cortical folding “I. ReSUltS Preliminary results suggested OP had significantly thinner cortex bilaterally in regions including the prefrontal cortex (near Brodmann Area [BA] 44), pre/postcentral regions (near BA 4/6), parietal (near BA 40/39), and occipital cortex (near BA 17/18) with a relative sparing of superior prefrontal cortex (e.g. near BA 8/9) and temporal lobes. The figure shows regions of statistically thinner cortex in OP with red to yellow indicating less to greater significance, respectively). Differences were preliminarily estimated between -0.25 to 0.50 mm. Aging is accompanied by thickness changes in prefrontal, somatosensory and occipital cortex. These conclusions must be considered with caution as there are potential confounds. Importantly, changes in tissue signal properties in aging and disease may contaminate measures of thickness. Additionally, larger groups of matched subjects should be examined. Nonetheless, these preliminary results suggest great promise for using cortical thickness measures to detect preclinical dementia and anatomic changes associated with cognitive decline [91.

Child maltreatment increases the risk for psychiatric disorders throughout childhood and into adulthood. One negative outcome of child maltreatment can be a disorder of emotional functioning, reactive attachment disorder (RAD), where the child displays wary, watchful, and emotionally withdrawn behaviours. Despite its clinical importance, little is known about the potential neurobiological consequences of RAD. The aim of this study was to elucidate whether RAD was associated with alterations in grey matter volume (GMV). High-resolution magnetic resonance imaging datasets were obtained for children and adolescents with RAD (n = 21; mean age = 12.76 years) and typically developing (TD) control subjects (n = 22; mean age = 12.95 years). Using a whole-brain voxel-based morphometry approach, structural images were analysed controlling for age, gender, full scale intelligence quotient, and total brain volume. The GMV was significantly reduced by 20.6% in the left primary visual cortex (Brodmann area 17) of the RAD group compared to the TD group (p = .038, family-wise error-corrected cluster level). This GMV reduction was related to an internalising problem measure of the Strength and Difficulties Questionnaire. The visual cortex has been viewed as part of the neurocircuit regulating the stress response to emotional visual images. Combined with previous studies of adults with childhood maltreatment, early adverse experience (e.g. sensory deprivation) may affect the development of the primary visual system, reflecting in the size of the visual cortex in children and adolescents with RAD. These visual cortex GMV abnormalities may also be associated with the visual emotion regulation impairments of RAD, leading to an increased risk for later psychopathology., Highlights • We examined grey matter alterations in reactive attachment disorder (RAD). • Grey matter volume (GMV) was analysed using whole-brain voxel-based morphometry. • Reduced visual cortex GMV was shown in RAD children compared to control children. • Visual cortex GMV of RAD children was related to their internalising problems. • The structural alterations in RAD may be due to emotion regulation impairments.

The development of positron emission tomography (PET) is of great interest in the study of psychiatric disorders. In comparison with other functional imaging techniques PET has a better resolution and makes it also possible to study both cortical and subcortical structures three dimensionally. Of the psychiatric disorders, schizophrenia has attracted the most interest. The main reason for this are the character of the disease like disturbed thinking, hallucinations, delusions and the development of social incapability and the number of neurobiological disturbances found in the patients.

There is firstly an account of the areas of the cerebral cortex that are concerned in speech, the anterior speech area of Broca, and the large pos- terior speech area of Wernicke (Fig. E4 — 1). These areas were originally defined by astute inferences from cortical lesions in patients that suffered various kinds of aphasia. The remarkable discovery was that about 95% of aphasics have lesions in their left cerebral hemisphere. Experiments on exposed human brains have confirmed these earlier clinical studies and sharpened the localizations of the speech area, showing in particular that the Wernicke area extended up into areas 39 and 40 of the parietal lobe (Fig.E4-3).

An introduction to the essential neuronal structure of the cerebral cortex, leads on to an account of its modular structure as revealed by radiotracer and degeneration techniques. Each module is a column of a few thousand nerve cells that is vertically oriented across the cerebral cortex, being about 0.25 mm across and 2 to 3 mm long. These modules are now recognized to be the functional units of communication throughout the association cortex, which forms 95% of the human neocortex. It is therefore of the greatest importance to consider the manner in which these modular units, about four million in number, contribute to the total performance of the human cerebrum.

The purposes of the investigation were to determine whether there was significant neuronal loss in dementia, and if so, whether it was general or localised, and to examine the relationship between neuronal counts, senile plaques and neurofibrillary change. Neuronal counts were made in nine cortical areas in the brains of 25 patients with senile dementia of the Alzheimer type and twenty-five age-matched controls, with the aid of an image analysing computer. Neuronal counts per square millimetre were significantly lower in the demented group of patients in the inferior frontal and superior temporal gyri. Neuronal counts in four columns of cortex were significantly reduced in superior, middle and inferior frontal gyri, cingulate gyrus and superior and middle temporal gyri. There was no significant difference in the parietal (Brodmann area 7) or occipital (Brodmann area 17) cortex. Corresponding glial counts per square millimetre show a significant increase in the demented group only in the middle and inferior temporal gyri. Neuronal counts correlated weakly but significantly with plaque counts in the same cortical area in the middle frontal gyrus and the superior and middle temporal gyri. High correlations between neuronal counts and estimates of neurofibrillary change were found in superior, middle and inferior frontal gyri, cingulate gyrus and superior and middle temporal gyri.

The striatum was found to exhibit marked variation in the severity of neuropathological involvement in post mortem brain specimens from 163 clinically diagnosed cases of Huntington’s disease (HD). A grading system was established by macroscopic and microscopic criteria, resulting in five grades (0–4) designated in ascending order of severity. The earliest changes were seen in the medial caudate nucleus (CN), in the tail of the CN, and in the dorsal part of the putamen. The grade correlated with the extent of clinical disability as assessed by a rating scale. Quantitative measurements revealed a 50% neuronal loss in the CN in grade 1 and a 95% loss in grade 4. Astrocytes are greatly increased in grades 2–4. Analyses of the CN in grade 4 reflect mainly astrocytic composition with a component of remote neurons projecting to the striatum. Because of the relative preservation of the lateral half of the head of the CN in grades 1–2, these regions would reflect early cellular and biochemical changes in HD.

Since about two years, the PET-scan group at the Karolinska institute in Stockholm has been engaged in analysing various aspects of brain function in schizophrenic patients using the PET-scan technique. Most studies performed so far have concerned the use of 11-C-labelled glucose to study brain energy metabolism (Blomqvist et al., 1983). The studies reported in a preliminary form in this communication had the following objectives: (1) To compare regional brain net uptake of 11-C in schizophrenic patients and healthy volunteers after intravenous injection of 11-C-glucose. (2) Examine variability of metabolic data obtained from two measurements in healthy volunteers. (3) Examine the effect of a standardized neuroleptic treatment (sulpiride) on regional glucose metabolism in schizophrenic patients. (4) Explore the possibility to visualize brain dopamine receptors in monkeys using 11-C-labelled substituted benzamides.

We progress to smaller systems. Theory and psychophysical mapping suggested a level of central nervous system (CNS) processing for synesthesia. An examination of similar phenomena indicated the anatomical site of the temporal-limbic region. We now consider what the neural basis of synesthesia might be.

The present functional magnetic resonance imaging (fMRI) study was designed to get a better understanding of the brain regions involved in sustained spatial attention to tactile events and to ascertain to what extent their activation was correlated. We presented continuous 20 Hz vibrotactile stimuli (range of flutter) concurrently to the left and right index fingers of healthy human volunteers. An arrow cue instructed subjects in a trial-by-trial fashion to attend to the left or right index finger and to detect rare target events that were embedded in the vibrotactile stimulation streams. We found blood oxygen level-dependent (BOLD) attentional modulation in primary somatosensory cortex (SI), mainly covering Brodmann area 1, 2, and 3b, as well as in secondary somatosensory cortex (SII), contralateral to the to-be-attended hand. Furthermore, attention to the right (dominant) hand resulted in additional BOLD modulation in left posterior insula. All of the effects were caused by an increased activation when attention was paid to the contralateral hand, except for the effects in left SI and insula. In left SI, the effect was related to a mixture of both a slight increase in activation when attention was paid to the contralateral hand as well as a slight decrease in activation when attention was paid to the ipsilateral hand (i.e., the tactile distraction condition). In contrast, the effect in left posterior insula was exclusively driven by a relative decrease in activation in the tactile distraction condition, which points to an active inhibition when tactile information is irrelevant. Finally, correlation analyses indicate a linear relationship between attention effects in intrahemispheric somatosensory cortices, since attentional modulation in SI and SII were interrelated within one hemisphere but not across hemispheres. All in all, our results provide a basis for future research on sustained attention to continuous vibrotactile stimulation in the range of flutter.

A better understanding of gait disorders that are associated with aging is crucial to prevent adverse outcomes. The functional study of gait remains a thorny issue due to technical constraints inherent to neuroimaging procedures, as most of them require to stay supine and motionless. Using an MRI-compatible system of boots reproducing gait-like plantar stimulation, we investigated the correlation between age and brain fMRI activation during simulated gait in healthy adults. Sixty-seven right-handed healthy volunteers aged between 20 and 77 years old (49.2 ± 18.0 years; 35 women) were recruited. Two paradigms were assessed consecutively: (a) gait-like plantar stimulation and (b) chaotic and not gait-related plantar stimulation. Resulting statistical parametric maps were analyzed with a multiple-factor regression that included age and a threshold determined by Monte-Carlo simulation to fulfill a family-wise error rate correction of p

The frontal pole corresponds to Brodmann area (BA) 10, the largest single architectonic area in the human frontal lobe. Generally, BA10 is thought to contain two or three subregions that subserve broad functions such as multitasking, social cognition, attention, and episodic memory. However, there is a substantial debate about the functional and structural heterogeneity of this large frontal region. Previous connectivity-based parcellation studies have identified two or three subregions in the human frontal pole. Here, we used diffusion tensor imaging to assess structural connectivity of BA10 in 35 healthy subjects and delineated subregions based on this connectivity. This allowed us to determine the correspondence of structurally based subregions with the scheme previously defined functionally. Three subregions could be defined in each subject. However, these three subregions were not spatially consistent between subjects. Therefore, we accepted a solution with two subregions that encompassed the lateral and medial frontal pole. We then examined resting-state functional connectivity of the two subregions and found significant differences between their connectivities. The medial cluster was connected to nodes of the default-mode network, which is implicated in internally focused, self-related thought, and social cognition. The lateral cluster was connected to nodes of the executive control network, associated with directed attention and working memory. These findings support the concept that there are two major anatomical subregions of the frontal pole related to differences in functional connectivity.

Six subjects underwent PET scans while they performed three versions of a recognition memory test for words and three versions of a control task. In each memory condition, the subjects discriminated between words presented in a prescan study list and words new to the experiment. During the 30 s scanning interval, the ratio of old and new words was 0: 20, 4: 16 or 16: 4, depending on the experimental condition. Outside this interval, the ratio was 50: 50 in all three conditions. The requirement in the control task was to discriminate between two character strings, the ratios of which were also manipulated during the 30 s scanning interval. Employing the control task as a covariate, analysis with statistical parametric mapping revealed that regional cerebral blood flow (rCBF) covaried with increasing density of old items in three regions of prefrontal cortex: right dorsolateral [Brodmann area (BA) 9/46], right medial (BA 32/8) and bilateral frontopolar cortex (BA 10). It is concluded that the prefrontal cortex, especially in the right hemisphere, is more active when a retrieval attempt succeeds than when it fails. This finding is consistent with the idea that the prefrontal cortex supports processes that operate selectively on the products of memory retrieval.

Events coupled with an emotional context seem to be better retained than non-emotional events. The aim of our study was to investigate whether an emotional context could influence the neural substrates of memory associations with novel portrait art stimuli. In the current prospective fMRI study, we have investigated for one specific visual art form (modern artistic portraits with a high degree of abstraction) whether memory is influenced by priming with emotional facial pictures. In total forty healthy female volunteers in the same age range were recruited for the study. Twenty of these women participated in a prospective brain imaging memory paradigm and were asked to memorize a series of similar looking, but different portraits. After randomization, for twelve participants (Group 1), a third of the portraits was emotionally primed with approach-related pictures (smiling baby faces), a third with withdrawal-related pictures (baby faces with severe dermatological conditions), and another third with neutral images. Group 2 consisted of eight participants and they were not primed. Then, during an fMRI session 2 h later, these portraits were viewed in random order intermixed with a set of new (previously unseen) ones, and the participants had to decide for each portrait whether or not they had already been seen. In a separate experiment, a different sample of twenty healthy females (Group 3) rated their mood after being exposed to the same art stimuli, without priming. The portraits did not evoke significant mood changes by themselves, supporting their initial neutral emotional character (Group 3). The correct decision on whether the portraits were Familiar of Unfamiliar led to similar neuronal activations in brain areas implicated in visual and attention processing for both groups (Groups 1 and 2). In contrast, whereas primed participants showed significant higher neuronal activities in the left midline superior frontal cortex (Brodmann area (BA) 6), unprimed volunteers displayed higher right medial frontal cortical (BA 10) activities. Furthermore, specifically in Group 1, correct retrieval of negatively primed portraits evoked increased neuronal activity in the left medial orbitofrontal cortex (BA 11) and in the right (posterior) insula, suggesting enhanced stress-related responses to the memory of withdrawal-related primed modern artistic portraits in this group. Our prospective memory data in healthy females indicate that, to reach a correct retrieval decision, different midline anterior neuronal networks are recruited for portraits that were emotionally primed than for the unprimed ones. Importantly, our results also suggest that the negative emotional context leads to the formation of associations that are reactivated during memory retrieval processes of the initially neutral art portraits. When correctly recognized, the portraits evoke neuronal activities consistent with the withdrawal-related character of the emotional visual stimuli with which they have been associated. Although our results show that abstract portrait art can be associated with emotional primes this doesn't mean that this effect is specific for art images.

Language is thought to represent one of the most complex cognitive functions in humans. Here we break down complexity of language to its most basic syntactic computation which hierarchically binds single words together to form larger phrases and sentences. So far, the neural implementation of this basic operation has only been inferred indirectly from studies investigating more complex linguistic phenomena. In the present sub-region based functional magnetic resonance imaging (fMRI) study we directly assessed the neuroanatomical nature of this process. Our results showed that syntactic phrases-compared to word-list sequences-corresponded to increased neural activity in the ventral-anterior portion of the left pars opercularis [Brodmann Area (BA) 44], whereas the adjacently located deep frontal operculum/anterior insula (FOP/aINS), a phylogenetically older and less specialized region, was found to be equally active for both conditions. Crucially, the functional activity of syntactic binding was confined to one out of five clusters proposed by a recent fine-grained sub-anatomical parcellation for BA 44, with consistency across individuals. Neuroanatomically, the present results call for a redefinition of BA 44 as a region with internal functional specializations. Neurocomputationally, they support the idea of invariance within BA 44 in the location of activation across participants for basic syntactic building processing.