Laminar distribution of the pathological changes in frontal and temporal cortex in 8 patients with progressive supranuclear palsy

OBJECTIVE: To determine the laminar distribution of the pathological changes in the cerebral cortex in progressive supranuclear palsy (PSP). METHOD: The distribution of the abnormally enlarged neurons (EN), surviving neurons, neurofibrillary tangles (NFT), glial inclusions (GI), tufted astrocytes (TA), and neuritic plaques (NP) were studied across the cortex in tau immunolabeled sections of frontal and temporal cortex in 8 cases of PSP. RESULTS: The distribution of the NFT was highly variable with no consistent pattern of laminar distribution. The GI were distributed either in the lower laminae or uniformly across the cortex. Surviving neurons exhibited either a density peak in the upper laminae or a bimodal distribution was present with density peaks in the upper and lower laminae. The EN and glial cell nuclei were distributed primarily in the lower cortical laminae. There were positive correlations between the densities of the EN and glial cell nuclei and negative correlations between the surviving neurons and glial cells. No correlations were present between the densities of the NFT and GI. CONCLUSION: Cortical pathology in PSP predominantly affects the lower laminae but may spread to affect the upper laminae in some cases. The NFT and GI may have different laminar distributions and gliosis occurs concurrently with neuronal enlargement.

Laminar degeneration of the frontal and temporal cortex in neuronal intermediate filament inclusion disease (NIFID): a study using a-internexin immunohistochemistry

Objective: To determine the laminar distribution of the pathological changes in the frontal and temporal lobe in neuronal intermediate filament inclusion disease (NIFID). Method: The distribution of the alpha-intenexin-positive neuronal cytoplasmic inclusions (NCI), surviving neurons, swollen achromatic neurons (SN) and glial cell nuclei was studied across the cortex in gyri of the frontal and temporal lobe in 10 cases of NIFID. Results: The distribution of the NCI was highly variable within different gyri, a peak in the upper cortex, a bimodal distribution with peaks of density in the upper and lower laminae, or no significant variation in density across the cortex. The surviving neurons were either bimodally distributed or exhibited no significant change in density across the cortex. The SN and glial cell nuclei were most abundant in the lower cortical laminae. In half of the gyri, variations in density of the NCI across the cortex were positively correlated with the SN. In some gyri, the surviving neurons were positively correlated with the SN and negatively correlated with the glial cell nuclei. In addition, the SN and glial cell nuclei were positively correlated in over half the gyri studied. Conclusion: The data suggest that frontal and temporal lobe degeneration in NIFID characterized by NCI, SN, neuronal loss and gliosis extends across the cortical laminae with considerable variation between cases and gyri. alpha-internexin-positive neurons in the upper laminae appear to be particularly vulnerable. The gliosis appears to be largely correlated with the appearance of SN and with neuronal loss and not related to the NCI.

Laminar distribution of Pick bodies, Pick cells and Alzheimer disease pathology in the frontal and temporal cortex in Pick's disease

Lesions in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) have distinct laminar distributions in the cortex. The objective of the present study was to test the hypothesis that the lesions characteristic of Pick's disease (PD) and AD have distinctly different laminar distributions in cases of PD. Hence, the laminar distribution of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) was studied in the frontal and temporal cortex in nine patients with PD. In 57% of analyses of individual cortical areas, the density of PB was maximal in the upper cortex while in 25% of analyses, the distribution of PB was bimodal with density peaks in the upper and lower cortex. The density of PC was maximal in the lower cortex in 77% of analyses while a bimodal distribution was present in 5% of analyses. The density of NFT was maximal in the upper cortex in 50% of analyses, in the lower cortex in 15% of analyses, with a bimodal distribution in 4% of analyses. The density of SP did not vary significantly with cortical depth in 86% of analyses. The vertical densities of PB and PC were negatively correlated in 12/21 (57%) of brain areas. The maximum density of PB in the upper cortex was positively correlated with the maximum density of PC in the lower cortex. In 17/25 (68%) of brain areas, there was no significant correlation between the vertical densities of PB and NFT. The data suggest that the pathogenesis of PB may be related to that of the PC. In addition, although in many areas PB and NFT occur predominantly in the upper cortex, the two lesions appeared to affect different neuronal populations.

Cerebral Cortex Involvement In Machado-joseph Disease.

Machado-Joseph disease (MJD/SCA3) is the most frequent spinocerebellar ataxia, characterized by brainstem, basal ganglia and cerebellar damage. Few magnetic resonance imaging based studies have investigated damage in the cerebral cortex. The objective was to determine whether patients with MJD/SCA3 have cerebral cortex atrophy, to identify regions more susceptible to damage and to look for the clinical and neuropsychological correlates of such lesions. Forty-nine patients with MJD/SCA3 (mean age 47.7 ± 13.0 years, 27 men) and 49 matched healthy controls were enrolled. All subjects underwent magnetic resonance imaging scans in a 3 T device, and three-dimensional T1 images were used for volumetric analyses. Measurement of cortical thickness and volume was performed using the FreeSurfer software. Groups were compared using ancova with age, gender and estimated intracranial volume as covariates, and a general linear model was used to assess correlations between atrophy and clinical variables. Mean CAG expansion, Scale for Assessment and Rating of Ataxia (SARA) score and age at onset were 72.1 ± 4.2, 14.7 ± 7.3 and 37.5 ± 12.5 years, respectively. The main findings were (i) bilateral paracentral cortex atrophy, as well as the caudal middle frontal gyrus, superior and transverse temporal gyri, and lateral occipital cortex in the left hemisphere and supramarginal gyrus in the right hemisphere; (ii) volumetric reduction of basal ganglia and hippocampi; (iii) a significant correlation between SARA and brainstem and precentral gyrus atrophy. Furthermore, some of the affected cortical regions showed significant correlations with neuropsychological data. Patients with MJD/SCA3 have widespread cortical and subcortical atrophy. These structural findings correlate with clinical manifestations of the disease, which support the concept that cognitive/motor impairment and cerebral damage are related in disease.

5 Hz repetitive TMS increases anticipatory motor activity in the human cortex

In the present study, we analyzed how high-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor hand area (M1-Hand) shapes anticipatory motor activity in frontal areas as indexed by the contingent negative variation (CNV). Eight right-handed volunteers received real or sham 5 Hz rTMS at an intensity of 90% resting motorthreshold (1500 stimuli per session). Real but not sham rTMS to left M1-Hand induced a site-specific increase in amplitude of the late component of the CNV at the electrode C3 overlaying the site of stimulation. The increase in pre-movement activity in the stimulated cortex may reflect an increase in facilitatory drive from connected motor areas, enhanced responsiveness of the stimulated cortex to these inputs or both. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Executive "brake failure" following deactivation of human frontal lobe

In the course of daily living, humans frequently encounter situations in which a motor activity, once initiated, becomes unnecessary or inappropriate. Under such circumstances, the ability to inhibit motor responses can be of vital importance. Although the nature of response inhibition has been studied in psychology for several decades, its neural basis remains unclear. Using transcranial magnetic stimulation, we found that temporary deactivation of the pars opercularis in the right inferior frontal gyrus selectively impairs the ability to stop an initiated action. Critically, deactivation of the same region did not affect the ability to execute responses, nor did it influence physiological arousal. These findings confirm and extend recent reports that the inferior frontal gyrus is vital for mediating response inhibition.

The frontal assessment battery (FAB) reveals neurocognitive dysfunction in substance-dependent individuals in distinct executive domains: Abstract reasoning, motor programming, and cognitive flexibility

Substance-dependence is highly associated with executive cognitive function (ECF) impairments. However. considering that it is difficult to assess ECF clinically, the aim of the present study was to examine the feasibility of a brief neuropsychological tool (the Frontal Assessment Battery FAB) to detect specific ECF impairments in a sample of substance-dependent individuals (SDI). Sixty-two subjects participated in this study. Thirty DSM-IV-diagnosed SDI, after 2 weeks of abstinence, and 32 healthy individuals (control group) were evaluated with FAD and other ECF-related tasks: digits forward (DF), digits backward (DB), Stroop Color Word Test (SCWT), and Wisconsin Card Sorting Test (WCST). SDI did not differ from the control group on sociodemographic variables or IQ. However, SDI performed below the controls in OF, DB, and FAB. The SDI were cognitively impaired in 3 of the 6 cognitive domains assessed by the FAB: abstract reasoning, motor programming, and cognitive flexibility. The FAB correlated with DF, SCWT, and WCST. In addition, some neuropsychological measures were correlated with the amount of alcohol, cannabis, and cocaine use. In conclusion, SDI performed more poorly than the comparison group on the FAB and the FAB`s results were associated with other ECF-related tasks. The results suggested a negative impact of alcohol, cannabis, and cocaine use on the ECF. The FAB may be useful in assisting professionals as an instrument to screen for ECF-related deficits in SDI. (C) 2010 Elsevier Ltd. All rights reserved.

Frontal Assessment Battery (FAB) is a simple tool for detecting executive deficits in chronic cannabis users

Background: Cannabis is the most used illicit drug in the world, and its use has been associated with prefrontal cortex (PFC) dysfunction, including deficits in executive functions (EF). Considering that EF may influence treatment outcome, it would be interesting to have a brief neuropsychological battery to assess EF in chronic cannabis users (CCU). In the present study, the Frontal Assessment Battery (FAB), a brief, easy to use neuropsychological instrument aimed to evaluate EF, was used to evaluate cognitive functioning of CCU. Methods: We evaluated 107 abstinent CCU with the FAB and compared with 44 controls matched for age, estimated IQ, and years of education. Results: CCU performed poorly as compared to controls (FAB total score = 16.53 vs. 17.09, p .05). CCU had also a poor performance in the Motor Programming subtest (2.47 vs. 2.73, p .05). Conclusion: This study examined effects of cannabis in executive functioning and showed evidence that the FAB is sensitive to detect EF deficits in early abstinent chronic cannabis users. Clinical significance of these findings remains to be investigated in further longitudinal studies. FAB may be useful as a screening instrument to evaluate the necessity for a complete neuropsychological assessment in this population.

A Voxel-Based Morphometry Study of Frontal Gray Matter Correlates of Impulsivity

Impulsivity is a personality trait exhibited by healthy individuals, but excessive impulsivity is associated with some mental disorders. Lesion and functional, neuroimaging Studies indicate that the ventromedial prefrontal region (VMPFC), including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and medial prefrontal cortex, and the amygdala may modulate impulsivity and aggression. However, no morphometric study has examined the association between VMPFC and impulsivity. We hypothesized that healthy subjects with high impulsivity would have smaller volumes in these brain regions compared with those with low impulsivity. Sixty-two healthy Subjects were Studied (age 35.4 +/- 12.1 years) using a 1.5-T MRI system. The Barratt impulsiveness scale (BIS) was used to assess impulsivity. Images were processed using an optimized voxel-based morphometry (VBM) protocol. We calculated the correlations between BIS scale scores and the gray matter (GM) and white matter (WM) volumes of VMPFC and amygdala. GM volumes of the left and right OFC were inversely correlated with the BIS total score (P = 0.04 and 0.02, respectively). Left ACC GM Volumes had a tendency to be inversely correlated with the BIS total score (P = 0.05. Right OFC GM Volumes were inversely correlated with BIS nonplanning impulsivity, and left OFC GM volumes were inversely correlated with motor impulsivity. There were no significant WM volume correlations with impulsivity. The results Of this morphometry Study indicate that small OFC volume relate to high impulsivity and extend the prior finding that the VMPFC is involved in the circuit modulating impulsivity. HUM Brain Mapp 30:1188-1195, 2009. (C) 2008 Wiley-Liss, Inc.

Performance of patients with refractory obsessive-compulsive disorder in the Frontal Systems Behavior Scale

Objective: To compare the performance of patients with obsessive-compulsive disorder (OCD) refractory to conventional treatments to healthy controls according to the Frontal Systems Behaviour Scale (FrSBe), comparing the scale scores within each group (Self or Family) and correlating FrSBe with Y-BOCS, DY-BOCS, tic disorder and age of first symptoms. Method: Twenty OCD patients and 20 healthy controls were assessed using the FrSBe, a scale designed to evaluate frontal syndromes. Results: The patients had higher scores when compared with the control group (p value .001) in terms of total score on the scale for both profile forms (Self and Family). In addition, there was a significant difference between the scores reported by the patients and their respective relatives. However, no correlation was observed between the scale and the other variables. Conclusions: The scale was able to clearly differentiate patients with OCD from healthy controls. This finding suggests that the FrSBe can be used not only in neurologic patients but also in psychiatric cases such as refractory OCD.

The role of the right parietal cortex in sound localization: a chronometric single pulse transcranial magnetic stimulation study.

Auditory spatial functions, including the ability to discriminate between the positions of nearby sound sources, are subserved by a large temporo-parieto-frontal network. With the aim of determining whether and when the parietal contribution is critical for auditory spatial discrimination, we applied single pulse transcranial magnetic stimulation on the right parietal cortex 20, 80, 90 and 150 ms post-stimulus onset while participants completed a two-alternative forced choice auditory spatial discrimination task in the left or right hemispace. Our results reveal that transient TMS disruption of right parietal activity impairs spatial discrimination when applied at 20 ms post-stimulus onset for sounds presented in the left (controlateral) hemispace and at 80 ms for sounds presented in the right hemispace. We interpret our finding in terms of a critical role for controlateral temporo-parietal cortices over initial stages of the building-up of auditory spatial representation and for a right hemispheric specialization in integrating the whole auditory space over subsequent, higher-order processing stages.

Primary motor cortex involvement in Alzheimer disease.

In Alzheimer disease (AD) the involvement of entorhinal cortex, hippocampus, and associative cortical areas is well established. Regarding the involvement of the primary motor cortex the reported data are contradictory. In order to determine whether the primary motor cortex is involved in AD, the brains of 29 autopsy cases were studied, including, 17 cases with severe cortical AD-type changes with definite diagnoses of AD, 7 age-matched cases with discrete to moderate cortical AD-type changes, and 5 control cases without any AD-type cortical changes. Morphometric analysis of the cortical surface occupied by senile plaques (SPs) on beta-amyloid-immunostained sections and quantitative analysis of neurofibrillary tangles (NFTs) on Gallyas-stained sections was performed in 5 different cortical areas including the primary motor cortex. The percentage of cortical surface occupied by SPs was similar in all cortical areas, without significant difference and corresponded to 16.7% in entorhinal cortex, 21.3% in frontal associative, 16% in parietal associative, and 15.8% in primary motor cortex. The number of NFTs in the entorhinal cortex was significantly higher (41 per 0.4 mm2), compared with those in other cortical areas (20.5 in frontal, 17.9 in parietal and 11.5 in the primary motor cortex). Our findings indicate that the primary motor cortex is significantly involved in AD and suggest the appearance of motor dysfunction in late and terminal stages of the disease.

Mapping the structural core of human cerebral cortex.

Structurally segregated and functionally specialized regions of the human cerebral cortex are interconnected by a dense network of cortico-cortical axonal pathways. By using diffusion spectrum imaging, we noninvasively mapped these pathways within and across cortical hemispheres in individual human participants. An analysis of the resulting large-scale structural brain networks reveals a structural core within posterior medial and parietal cerebral cortex, as well as several distinct temporal and frontal modules. Brain regions within the structural core share high degree, strength, and betweenness centrality, and they constitute connector hubs that link all major structural modules. The structural core contains brain regions that form the posterior components of the human default network. Looking both within and outside of core regions, we observed a substantial correspondence between structural connectivity and resting-state functional connectivity measured in the same participants. The spatial and topological centrality of the core within cortex suggests an important role in functional integration.

False recognition following frontal lobe damage: The role of encoding factors

This paper reports a series of experiments on patient JB, a man with memory difficulties following damage to the left frontal lobe. The primary characteristic of JB's recognition memory impairment is a high level of false recognition together with a normal hit rate. The hypothesis that JB's false recognition reflects an over-reliance on familiarity is considered, but discounted on the basis that the false alarm rate is not affected by increasing the similarity between distracters and targets, and remains high when nonword stimuli are used. It is suggested, instead, that JB relies on a poorly focused memory description, which lacks item-specific detail but contains more general, low-level properties of the target items-these properties being held by many distracter items as well. This deficit is considered to arise because of damage to frontally mediated control processes involved in the selection of elements for memory encoding. An encoding deficit is supported by the fact that JB's false recognition is significantly reduced by orienting instructions, and is eliminated when his remote memory is subjected to recognition testing. In contrast, it is shown that manipulations at the level of retrieval (e.g. restricting the number of "old" responses) have little effect on his false recognition.

Changes in volume, surface estimate, three-dimensional shape and total number of neurons of the human primary visual cortex from midgestation until old age.

Macroscopic features such as volume, surface estimate, thickness and caudorostral length of the human primary visual cortex (Brodman's area 17) of 46 human brains between midgestation and 93 years were studied by means of camera lucida drawings from serial frontal sections. Individual values were best fitted by a logistic function from midgestation to adulthood and by a regression line between adulthood and old age. Allometric functions were calculated to study developmental relationships between all the features. The three-dimensional shape of area 17 was also reconstructed from the serial sections in 15 cases and correlated with the sequence of morphological events. The sulcal pattern of area 17 begins to develop around 21 weeks of gestation but remains rather simple until birth, while it becomes more convoluted, particularly in the caudal part, during the postnatal period. Until birth, a large increase in cortical thickness (about 83% of its mean adult value) and caudorostral length (69%) produces a moderate increase in cortical volume (31%) and surface estimate (40%) of area 17. After birth, the cortical volume and surface undergo their maximum growth rate, in spite of a rather small increase in cortical thickness and caudorostral length. This is due to the development of the pattern of gyrification within and around the calcarine fissure. All macroscopic features have reached the mean adult value by the end of the first postnatal year. With aging, the only features to undergo significant regression are the cortical surface estimate and the caudorostral length. The total number of neurons in area 17 shows great interindividual variability at all ages. No decrease in the postnatal period or in aging could be demonstrated.