Posterior Temporo-parietal Regions Research Articles

Tau epicenter identification and connectivity in clinically heterogeneous Alzheimer’s disease variants

AbstractBackgroundWhile the spread of tau throughout the brain is well‐characterized in amnestic Alzheimer’s disease (AD), tau staging remains less clear for those suffering from clinically heterogeneous variants including logopenic variant primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA). We created a method to identify local maxima of tau SUVR (“epicenters”) in participants with early‐stage clinically heterogeneous AD with the goal of classifying participant subtypes based on the functional connectivity of these epicenters.MethodWe obtained 18F‐MK‐6240 tau PET scans from 10 participants with diagnoses of early‐stage clinically heterogeneous AD (5 lvPPA, 5 PCA, Clinical Dementia Rating 0.5‐1.0). We identified three local maxima of tau SUVR with a minimum specified distance of 20mm between them for each participant (Fig. 1). We then derived each epicenter’s functional connectivity in 1000 healthy controls using Neurosynth and sorted participants into subtypes based on the overlap of these functional connectivity maps.ResultParticipants with lvPPA showed highest tau burden in the posterior temporoparietal and temporoocciptal regions, left side predominant, and participants with PCA displayed highest tau burden in the bilateral parietooccipital cortex, frontal eye fields, and fusiform gyrus. We identified nine distinct subtypes of functional connectivity and most participants’ epicenters participated in more than one subtype. All subtypes highlight functional connectivity networks that have been associated with language and, or visuospatial processing. The most common subtype (seen in 7 of the 10 participants and 11 of the 30 epicenters) features connectivity within the bilateral occipital lobule, fusiform gyrus, and superior parietal lobule (Fig. 2).ConclusionWe used a novel method to identify tau “epicenters” in the brains of participants with early‐stage clinically heterogeneous AD. Using these epicenters, we derived functional connectivity maps, which we then grouped into nine subtypes across participants. We will shortly begin collecting longitudinal tau PET in these clinically heterogeneous individuals with AD, allowing us to assess the extent to which tau spreads along the functional connectivity maps predicted by each participant’s epicenters and whether individually tailored epicenters outperform subtype classification. This work could serve as the basis for patient‐specific biomarkers of expected disease spread in clinically heterogeneous AD.

A - 34 A Suspected Case of Early-Onset Frontal Variant of Alzheimer's Disease in a 64-Year-Old Male.

Early-onset frontal variant of Alzheimer's disease (fvAD) is characterized by apathy, disinhibition, and executive dysfunction. As such, fvAD is often difficult to clinically distinguish from behavioral variant frontotemporal dementia (bvFTD). However, research suggests that a differentiating feature among the two conditions is that fvAD typically presents with more pronounced memory impairment. Therefore, neuropsychological testing in the context of a comprehensive multidisciplinary assessment can be a valuable tool to aid with differential diagnosis. A 64-year-old male with gradually progressive difficulties in cognition and behavioral-emotional functioning over the past 8-9years presented to a multidisciplinary neurology clinic. MRI showed mild atrophy in the frontal, temporal, and parietal lobe regions. Concerns were raised by his neurologist for early-onset ad versus bvFTD so the patient was referred for neuropsychological evaluation. Neuropsychological testing showed a largely amnestic memory profile along with deficits in executive functioning and semantic fluency. His spouse endorsed concerns for apathy and executive dysfunction on a frontal system rating questionnaire in addition to concerns for disinhibition during the clinical interview. Taken together, the patient's profile appeared to be consistent with early-onset fvAD. Follow-up FDG-PET scan showed decreased uptake in the anteromesial temporal lobes, posterior cingulate cortices, and posterior temporoparietal regions which was consistent with an ad profile. Early-onset fvAD and bvFTD are often difficult to clinically distinguish from each other. However, neuropsychological testing in conjunction with comprehensive multidisciplinary assessment can serve an important role in helping to facilitate differential diagnosis for these two neurodegenerative disorders with overlapping features.

Mapping Cholinergic Synaptic Loss in Parkinson's Disease: An [18F]FEOBV PET Case-Control Study.

Cholinergic degeneration is strongly associated with cognitive decline in patients with Parkinson's disease (PD) but may also cause motor symptoms and olfactory dysfunction. Regional differences are striking and may reflect different PD related symptoms and disease progression patterns. To map and quantify the regional cerebral cholinergic alterations in non-demented PD patients. We included 15 non-demented PD patients in early-moderate disease stage and 15 age- and sex-matched healthy controls for [18F]FEOBV positron emission tomography imaging. We quantitated regional variations using VOI-based analyses which were supported by a vertex-wise cluster analysis. Correlations between imaging data and clinical and neuropsychological data were explored. We found significantly decreased [18F]FEOBV uptake in global neocortex (38%, p = 0.0002). The most severe reductions were seen in occipital and posterior temporo-parietal regions (p < 0.0001). The vertex-wise cluster analysis corroborated these findings. All subcortical structures showed modest non-significant reductions. Motor symptoms (postural instability and gait difficulty) and cognition (executive function and composite z-score) correlated with regional [18F]FEOBV uptake (thalamus and cingulate cortex/insula/hippocampus, respectively), but the correlations were not statistically significant after multiple comparison correction. A strong correlation was found between interhemispheric [18F]FEOBV asymmetry, and motor symptom asymmetry of the extremities (r = 0.84, p = 0.0001). Cortical cholinergic degeneration is prominent in non-demented PD patients, but more subtle in subcortical structures. Regional differences suggest uneven involvement of cholinergic nuclei in the brain and may represent a window to follow disease progression. The correlation between asymmetric motor symptoms and neocortical [18F]FEOBV asymmetry indicates that unilateral cholinergic degeneration parallels ipsilateral dopaminergic degeneration.

Modulating Gamma Oscillations Promotes Brain Connectivity to Improve Cognitive Impairment.

Dementia causes a substantial global economic burden, but effective treatment is lacking. Recently, studies have revealed that gamma-band waves of electrical brain activity, particularly 40 Hz oscillations, are closely associated with high-order cognitive functions and can activate microglia to clear amyloid-β deposition. Here, we found that compared with sham stimulation, applying 40-Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) over the bilateral angular gyrus in patients with probable Alzheimer's disease (AD; n = 37) resulted in up to 8 weeks of significantly improved cognitive function. Power spectral density analysis of the resting-state electroencephalography (EEG) demonstrated that 40-Hz rTMS modulated gamma-band oscillations in the left posterior temporoparietal region. Further testing with magnetic resonance imaging and TMS-EEG revealed the following: 40-Hz rTMS 1) prevented gray matter volume loss, 2) enhanced local functional integration within bilateral angular gyrus, as well as global functional integration in bilateral angular gyrus and the left middle frontal gyrus, 3) strengthened information flow from the left posterior temporoparietal region to the frontal areas and strengthened the dynamic connectivity between anterior and posterior brain regions. These findings demonstrate that modulating gamma-band oscillations effectively improves cognitive function in patients with probable AD by promoting local, long-range, and dynamic connectivity within the brain.

Temporo-parietal brain regions are involved in higher order object perception

Lesions to posterior temporo-parietal brain regions are associated with deficits in perception of global, hierarchical shapes, but also with impairments in the processing of objects presented under demanding viewing conditions. Evidence from neuroimaging studies and lesion patterns observed in patients with simultanagnosia and agnosia for object orientation suggest similar brain regions to be involved in perception of global shapes and processing of objects in atypical (‘non-canonical’) orientation. In a localizer experiment, we identified individual temporo-parietal brain areas involved in global shape perception and found significantly higher BOLD signals during the processing of non-canonical compared to canonical objects. In a multivariate approach, we demonstrated that posterior temporo-parietal brain areas show distinct voxel patterns for non-canonical and canonical objects and that voxel patterns of global shapes are more similar to those of objects in non-canonical compared to canonical viewing conditions. These results suggest that temporo-parietal brain areas are not only involved in global shape perception but might serve a more general mechanism of complex object perception. Our results challenge a strict attribution of object processing to the ventral visual stream by suggesting specific dorsal contributions in more demanding viewing conditions.

Visuospatial short-term and working memory disturbance in the primary progressive aphasias: Neuroanatomical and clinical implications

IntroductionPrimary progressive aphasia (PPA) comprises three main variants: logopenic (lv-PPA), non-fluent (nfv-PPA) and semantic variant (sv-PPA). Differentiating the language profiles of the PPA variants remains challenging, especially for lv-PPA and nfv-PPA. As such, diagnostic tools that do not rely on speech and language may offer some utility. Here, we investigated the short-term and working memory profiles of the PPA variants and typical Alzheimer's disease (AD), with a particular interest in the visuospatial system. We hypothesised visuospatial short-term and working memory would be more compromised in lv-PPA and AD than in the other PPA variants, and that this would relate to degeneration of posterior temporoparietal brain regions. MethodThirty-three lv-PPA, 26 nfv-PPA, 31 sv-PPA and 58 AD patients, and 45 matched healthy controls were recruited. All participants completed the WMS-III Spatial and Digit Span tasks and underwent a structural brain MRI for voxel-based morphometry analyses. ResultsRelative to Controls, Spatial Span Forward (SSF) performance was impaired in lv-PPA and AD but not in nfv-PPA or sv-PPA. In contrast, Digit Span Forward (DSF) performance was impaired in lv-PPA and nfv-PPA (to a similar level), and AD, but was relatively intact in sv-PPA. As expected, most backward span scores across both modalities were lower than forward span scores. Neuroimaging analyses revealed that SSF and SSB performance in all patients combined correlated with grey matter intensity decrease in several clusters located in temporo-parieto-occipital brain regions. Post-hoc group comparisons of these regions showed that grey matter loss was more extensive in the lv-PPA and AD groups than in the nfv-PPA and sv-PPA groups. ConclusionsThe findings suggest that the visuospatial short-term and working memory profiles of the PPA variants are separable and likely reflect their distinct patterns of temporo-parieto-occipital brain atrophy.

Microglial activation and tau burden predict cognitive decline in Alzheimer's disease.

Tau pathology, neuroinflammation, and neurodegeneration are key aspects of Alzheimer's disease. Understanding whether these features predict cognitive decline, alone or in combination, is crucial to develop new prognostic measures and enhanced stratification for clinical trials. Here, we studied how baseline assessments of in vivo tau pathology (measured by 18F-AV-1451 PET), neuroinflammation (measured by 11C-PK11195 PET) and brain atrophy (derived from structural MRI) predicted longitudinal cognitive changes in patients with Alzheimer's disease pathology. Twenty-six patients (n = 12 with clinically probable Alzheimer's dementia and n = 14 with amyloid-positive mild cognitive impairment) and 29 healthy control subjects underwent baseline assessment with 18F-AV-1451 PET, 11C-PK11195 PET, and structural MRI. Cognition was examined annually over the subsequent 3 years using the revised Addenbrooke's Cognitive Examination. Regional grey matter volumes, and regional binding of 18F-AV-1451 and 11C-PK11195 were derived from 15 temporo-parietal regions characteristically affected by Alzheimer's disease pathology. A principal component analysis was used on each imaging modality separately, to identify the main spatial distributions of pathology. A latent growth curve model was applied across the whole sample on longitudinal cognitive scores to estimate the rate of annual decline in each participant. We regressed the individuals' estimated rate of cognitive decline on the neuroimaging components and examined univariable predictive models with single-modality predictors, and a multi-modality predictive model, to identify the independent and combined prognostic value of the different neuroimaging markers. Principal component analysis identified a single component for the grey matter atrophy, while two components were found for each PET ligand: one weighted to the anterior temporal lobe, and another weighted to posterior temporo-parietal regions. Across the whole-sample, the single-modality models indicated significant correlations between the rate of cognitive decline and the first component of each imaging modality. In patients, both stepwise backward elimination and Bayesian model selection revealed an optimal predictive model that included both components of 18F-AV-1451 and the first (i.e. anterior temporal) component for 11C-PK11195. However, the MRI-derived atrophy component and demographic variables were excluded from the optimal predictive model of cognitive decline. We conclude that temporo-parietal tau pathology and anterior temporal neuroinflammation predict cognitive decline in patients with symptomatic Alzheimer's disease pathology. This indicates the added value of PET biomarkers in predicting cognitive decline in Alzheimer's disease, over and above MRI measures of brain atrophy and demographic data. Our findings also support the strategy for targeting tau and neuroinflammation in disease-modifying therapy against Alzheimer's disease.

Age-related differences in neural activation and functional connectivity during the processing of vocal prosody in adolescence.

The ability to recognize others' emotions based on vocal emotional prosody follows a protracted developmental trajectory during adolescence. However, little is known about the neural mechanisms supporting this maturation. The current study investigated age-related differences in neural activation during a vocal emotion recognition (ER) task. Listeners aged 8 to 19 years old completed the vocal ER task while undergoing functional magnetic resonance imaging. The task of categorizing vocal emotional prosody elicited activation primarily in temporal and frontal areas. Age was associated with a) greater activation in regions in the superior, middle, and inferior frontal gyri, b) greater functional connectivity between the left precentral and inferior frontal gyri and regions in the bilateral insula and temporo-parietal junction, and c) greater fractional anisotropy in the superior longitudinal fasciculus, which connects frontal areas to posterior temporo-parietal regions. Many of these age-related differences in brain activation and connectivity were associated with better performance on the ER task. Increased activation in, and connectivity between, areas typically involved in language processing and social cognition may facilitate the development of vocal ER skills in adolescence.

MICROGLIAL ACTIVATION AND TAU BURDEN PREDICT COGNITIVE DECLINE IN ALZHEIMER’S DISEASE

Neurodegeneration, tau pathology, and neuroinflammation are key etiopathogenic processes of Alzheimer's disease (AD). Understanding whether these features predict cognitive decline in AD is crucial to developing prognostic measures. We studied the independent prognostic value of atrophy (structural MRI), tau burden ([18F]AV-1451 PET), and neuroinflammation ([11C]PK-11195 PET) in predicting longitudinal cognitive decline in patients with AD dementia, and amyloid positive Mild Cognitive Impairment (MCI+). 29 healthy controls (HC) and 26 patients with AD pathology (12 AD and 14 MCI+) underwent a cross-sectional assessment with structural MRI, dynamic [11C]PK-11195, and [18F]AV-1451 PET imaging as part of the NIMROD study (NeuroImaging of MemoRy and Other related Disorders). An annual cognitive follow-up (using the Revised Addenbrooke's Cognitive Examination (ACE-R)) was performed for two years. Regional grey matter volumes were derived from structural MRI in AD-specific regions, while [18F]AV-1451 and [11C]PK-11195 non-displaceable specific binding were calculated for these volumes to quantify tau pathology and neuroinflammation. To reduce dimensionality of the data, we used a Principal Component Analysis (PCA) on each imaging method. A Latent Growth Curve model (LGCM) was used to test for the independent predictive value of the PCA-derived neuroimaging measures on longitudinal cognitive decline (Figure 1). PCA identified a global component for grey matter volumes, and two components for each PET ligand: one in anterior temporal regions, and another in posterior temporo-parietal regions (Figure 2). The LGCM using MRI (χ2(4)=2.82, p=0.59, RMSEA=0.00, CFI=1.00) showed a positive association between grey-matter volumes and longitudinal ACE-R scores (Std all=0.56, p<0.001). LGCM with [11C]PK-11195 (χ2(6)=1.50, p=0.96, RMSEA=0.00, CFI=1.00) indicated a positive association with 2-year cognitive decline in both anterior (Std all=−0.42, p<0.001) and posterior (Std all=−0.35, p=0.016) components. Furthermore, in LGCM with [18F]AV-1451 (χ2(6)=10.63, p=0.10, RMSEA=0.12, CFI=0.98), longitudinal cognitive performance correlated negatively with values in the posterior (Std all=−0.61, p=0.01) and anterior (Std all=−0.43, p<0.001) components.

Neuro-cognitive mechanisms of global Gestalt perception in visual quantification

Recent neuroimaging studies identified posterior regions in the temporal and parietal lobes as neuro-functional correlates of subitizing and global Gestalt perception. Beyond notable overlap on a neuronal level both mechanisms are remarkably similar on a behavioral level representing both a specific form of visual top-down processing where single elements are integrated into a superordinate entity. In the present study, we investigated whether subitizing draws on principles of global Gestalt perception enabling rapid top-down processes of visual quantification. We designed two functional neuroimaging experiments: a task identifying voxels responding to global Gestalt stimuli in posterior temporo-parietal brain regions and a visual quantification task on dot patterns with magnitudes within and outside the subitizing range. We hypothesized that voxels activated in global Gestalt perception should respond stronger to dot patterns within than those outside the subitizing range. The results confirmed this prediction for left-hemispheric posterior temporo-parietal brain areas. Additionally, we trained a classifier with response patterns from global Gestalt perception to predict neural responses of visual quantification. With this approach we were able to classify from TPJ Gestalt ROIs of both hemispheres whether a trial requiring subitizing was processed. The present study demonstrates that mechanisms of subitizing seem to build on processes of high-level visual perception.

Assessment of the visual acuity, contrast sensitivity, color vision and visual integration in the Alzheimer's Disease progression according to the scale GDS

PurposeAlzheimer's disease (AD) is characterized by an accumulation of abnormal plaques and tangles in the brain with cortical atrophy most pronounced in the medial temporal and posterior temporoparietal regions. The process is estimated to begin years before the appearance of clinical symptoms. The aim of this work was to investigate the potential use of ophthalmological psychophysical tests as AD follow‐up.MethodsTwenty‐six mild AD patients, 12 moderate AD and 32 controls underwent visual acuity (VA), contrast sensitivity (CS), colour perception tests and perception visual test (PDT). All patients were classified according the Global Deteriorate Scale (GDS).ResultsIn comparison with control: i) patients with mild AD presented a significant decrease in the VA, in the CS (for all the spatial frequencies), in the blue colour perception and in PDT; ii) patients with moderate AD showed the same result as the mild AD, compared with controls, furthermore a significant increase of the total number of errors in the colour test (p &lt; 0.05 in all instances). In comparison with mild AD, moderate AD patients had no statistical differences in CS, VA and PDT (p &gt; 0.05) but significant differences in the colour perception (total number of errors and unspecific blue axis errors) (p &lt; 0.05).ConclusionsIn comparison with the control group, patients with mild and moderate AD presented a statistically significant decrease in CS, for all the spatial frequencies (the higher the spatial frequency, the greater the loss of CS perception), and in the colour perception. Therefore AD patients, show alterations in the M, P, and K visual pathways. Psychophysical tests could be useful tools to diagnose support and follow‐up in mild AD.

Emergence of representations through repeated training on pronouncing novel letter combinations leads to efficient reading

Printed text can be decoded by utilizing different processing routes depending on the familiarity of the script. A predominant use of word-level decoding strategies can be expected in the case of a familiar script, and an almost exclusive use of letter-level decoding strategies for unfamiliar scripts. Behavioural studies have revealed that frequently occurring words are read more efficiently, suggesting that these words are read in a more holistic way at the word-level, than infrequent and unfamiliar words. To test whether repeated exposure to specific letter combinations leads to holistic reading, we monitored both behavioural and neural responses during novel script decoding and examined changes related to repeated exposure. We trained a group of Dutch university students to decode pseudowords written in an unfamiliar script, i.e., Korean Hangul characters. We compared behavioural and neural responses to pronouncing trained versus untrained two-character pseudowords (equivalent to two-syllable pseudowords). We tested once shortly after the initial training and again after a four days' delay that included another training session. We found that trained pseudowords were pronounced faster and more accurately than novel combinations of radicals (equivalent to letters). Imaging data revealed that pronunciation of trained pseudowords engaged the posterior temporo-parietal region, and engagement of this network was predictive of reading efficiency a month later. The results imply that repeated exposure to specific combinations of graphemes can lead to emergence of holistic representations that result in efficient reading. Furthermore, inter-individual differences revealed that good learners retained efficiency more than bad learners one month later.

Usefulness of ophthalmology psychophysical test for diagnosis and monitoring support in mild Alzheimer’s disease

AbstractPurpose Alzheimer’s disease (AD) is a neurodegenerative disorder of the central nervous system characterized by cortical atrophy most pronounced in the medial temporal and posterior temporoparietal regions. The goal of the present study was to examine the visual pathway in patients with mild AD (GDS 4) by means of a different psychophysical test, specifically —visual acuity (VA), contrast sensitivity (CS), colour perception and perception digital test (PDT)— and to compare them with an age‐matched control.Methods Twenty‐three patients with mild AD and 27 controls were examined at Hospital Clínico San Carlos in Madrid (Spain). Subjects underwent a complete ophthalmological examination (VA, refraction, colour test, biomicroscopy, IOP, dilated fundoscopy, and OCT).Results In comparison with the control group, patients with mild AD presented a significant decrease in the VA, in the CS (for all the spatial frequencies), in the colour perception (unspecific errors blue axis) and PDT (p &lt;0.05 in all instances).Conclusion In mild AD, there are alterations in the M, P, and K visual pathways. The psychophysical ophthalmological tests used in this study could serve as a tool for AD diagnosis and follow‐up. (Support: OFTARED (Grant RD12/0034/0002, ISCIII, Spanish Ministry of Science and Innovation)

Damage to ventral and dorsal language pathways in acute aphasia

Converging evidence from neuroimaging studies and computational modelling suggests an organization of language in a dual dorsal–ventral brain network: a dorsal stream connects temporoparietal with frontal premotor regions through the superior longitudinal and arcuate fasciculus and integrates sensorimotor processing, e.g. in repetition of speech. A ventral stream connects temporal and prefrontal regions via the extreme capsule and mediates meaning, e.g. in auditory comprehension. The aim of our study was to test, in a large sample of 100 aphasic stroke patients, how well acute impairments of repetition and comprehension correlate with lesions of either the dorsal or ventral stream. We combined voxelwise lesion-behaviour mapping with the dorsal and ventral white matter fibre tracts determined by probabilistic fibre tracking in our previous study in healthy subjects. We found that repetition impairments were mainly associated with lesions located in the posterior temporoparietal region with a statistical lesion maximum in the periventricular white matter in projection of the dorsal superior longitudinal and arcuate fasciculus. In contrast, lesions associated with comprehension deficits were found more ventral-anterior in the temporoprefrontal region with a statistical lesion maximum between the insular cortex and the putamen in projection of the ventral extreme capsule. Individual lesion overlap with the dorsal fibre tract showed a significant negative correlation with repetition performance, whereas lesion overlap with the ventral fibre tract revealed a significant negative correlation with comprehension performance. To summarize, our results from patients with acute stroke lesions support the claim that language is organized along two segregated dorsal–ventral streams. Particularly, this is the first lesion study demonstrating that task performance on auditory comprehension measures requires an interaction between temporal and prefrontal brain regions via the ventral extreme capsule pathway.

Lesions impairing regular versus irregular past tense production

We investigated selective impairments in the production of regular and irregular past tense by examining language performance and lesion sites in a sample of twelve stroke patients. A disadvantage in regular past tense production was observed in six patients when phonological complexity was greater for regular than irregular verbs, and in three patients when phonological complexity was closely matched across regularity. These deficits were not consistently related to grammatical difficulties or phonological errors but were consistently related to lesion site. All six patients with a regular past tense disadvantage had damage to the left ventral pars opercularis (in the inferior frontal cortex), an area associated with articulatory sequencing in prior functional imaging studies. In addition, those that maintained a disadvantage for regular verbs when phonological complexity was controlled had damage to the left ventral supramarginal gyrus (in the inferior parietal lobe), an area associated with phonological short-term memory. When these frontal and parietal regions were spared in patients who had damage to subcortical (n = 2) or posterior temporo-parietal regions (n = 3), past tense production was relatively unimpaired for both regular and irregular forms. The remaining (12th) patient was impaired in producing regular past tense but was significantly less accurate when producing irregular past tense. This patient had frontal, parietal, subcortical and posterior temporo-parietal damage, but was distinguished from the other patients by damage to the left anterior temporal cortex, an area associated with semantic processing. We consider how our lesion site and behavioral observations have implications for theoretical accounts of past tense production.

A semi-quantitative method for correlating brain disease groups with normal controls using SPECT: Alzheimer's disease versus vascular dementia

PurposeTo demonstrate the utility of semi-quantitative circumferential-profile analysis of regional cerebral blood flow (rCBF) SPECT in Alzheimer's disease (AD) versus white matter vascular dementia (WM-VaD). MethodsSubjects underwent dementia evaluation, MRI and Tc-99m HMPAO SPECT. rCBF patterns from 11 AD and 20 WM-VaD patients were compared to 17 controls using semi-quantitative circumferential-profile analysis. ResultsAD patients showed more significant semi-quantitative circumferential-profile reductions in the posterior temporo-parietal regions, whereas WM-VaD patients demonstrated greater reductions involving the frontal regions of the brain. ConclusionSemi-quantitative circumferential-profile analysis provides a practical semi-quantitative method to evaluate brain SPECT scans in AD versus WM-VaD patients.

A common 8q (MYC) amplification detected in a multifocal anaplastic astrocytoma by SNP array karyotyping

The distinction of multifocal versus multicentric gliomas can conceivably have important therapeutic implications. We present a 27-year-old man with two radiologically distinct non-enhancing infiltrative masses in the anterior frontal lobe and the posterior temporoparietal region. No intervening disease was evident on MRI modalities; the lesions were stable over a period of many months. He underwent two separate resections a few months apart. Given the question of whether his tumors represented two de novo primary multicentric tumors or one multifocal tumor, single nucleotide polymorphism (SNP) array karyotyping and in situ hybridization studies were performed on both tumors. The two tumor profiles looked remarkably similar, histologically and genetically: both were anaplastic astrocytomas with a common 33Mb gain/ amplification of 8q23.3-q24.3, including MYC amplification, suggesting a monoclonal origin. The temporoparietal neoplasm showed several additional genetic alterations. This case illustrates that even with today's advanced neuroimaging modalities, extensive radiologically invisible tumor may be present between seemingly separate sites of glioma involvement. Thus modern global genomic studies of such tumors may help distinguish whether multiple tumors represent one extensive neoplasm with microscopically invasive disease or multiple genetically distinct tumors.

Language regions of brain are operative in color perception.

The effect of language on the categorical perception of color is stronger for stimuli in the right visual field (RVF) than in the left visual field, but the neural correlates of the behavioral RVF advantage are unknown. Here we present brain activation maps revealing how language is differentially engaged in the discrimination of colored stimuli presented in either visual hemifield. In a rapid, event-related functional MRI study, we measured subjects' brain activity while they performed a visual search task. Compared with colors from the same lexical category, discrimination of colors from different linguistic categories provoked stronger and faster responses in the left hemisphere language regions, particularly when the colors were presented in the RVF. In addition, activation of visual areas 2/3, responsible for color perception, was much stronger for RVF stimuli from different linguistic categories than for stimuli from the same linguistic category. Notably, the enhanced activity of visual areas 2/3 coincided with the enhanced activity of the left posterior temporoparietal language region, suggesting that this language region may serve as a top-down control source that modulates the activation of the visual cortex. These findings shed light on the brain mechanisms that underlie the hemifield- dependent effect of language on visual perception.

Argument structure effects in action verb naming in static and dynamic conditions

Argument structure, as in the participant roles entailed within the lexical representation of verbs, affects verb processing. Recent neuroimaging studies show that when verbs are heard or read, the posterior temporoparietal region shows increased activation for verbs with greater versus lesser argument structure complexity, usually bilaterally. In addition, patients with agrammatic aphasia show verb production deficits, graded based on argument structure complexity. In the present study, we used fMRI to examine the neural correlates of verb production in overt action naming conditions. In addition, we tested the differential effects of naming when verbs were presented dynamically in video segments versus statically in line drawings. Results showed increased neuronal activity associated with production of transitive as compared to intransitive verbs not only in posterior regions, but also in left inferior frontal cortex. We also found significantly greater activation for transitive versus intransitive action naming for videos compared to pictures in the right inferior and superior parietal cortices, areas associated with object manipulation. These findings indicate that verbs with greater argument structure density engender graded activation of both anterior and posterior portions of the language network and support verb naming deficit patterns reported in lesion studies. In addition, the similar findings derived under video and static picture naming conditions provide validity for using videos in neuroimaging studies, which are more naturalistic and perhaps ecologically valid than using static pictures to investigate action naming.

Naming Is Associated with Left Temporal Pole Metabolite Levels in Neurodegenerative Diseases

Aim: To investigate the relationship between performance in language tests and levels of brain metabolites in two selected left temporal lobe regions. Methods: Ninety-five subjects were included: 26 controls, 30 amnestic mild cognitive impairment subjects, 27 Alzheimer’s disease and 12 frontotemporal lobar degeneration (FTLD) patients. Language was assessed by a naming test: Boston Naming Test (BNT) and by a semantic verbal fluency test. Other cognitive functions: verbal and visual memory, visual perception, attention and executive function, and praxis were also assessed. Single voxel magnetic resonance spectroscopy was obtained in the left temporal pole (L-TPOLE), and in the left posterior temporoparietal region (L-TPAR). Results: BNT scores were significantly associated with N-acetylaspartate/creatine ratios (r = 0.45; p < 0.001) and choline/creatine ratios (r = 0.33; p < 0.005) in the L-TPOLE. No significant associations were found between BNT and metabolite levels in the L-TPAR. No significant associations were found between the semantic verbal fluency test and other cognitive tests and metabolite levels either in the L-TPOLE or in the L-TPAR. Conclusion: Naming performance is related to metabolite levels in the anterior L-TPOLE.