Middle Frontal Regions Research Articles

Association Between Learning Capabilities and Practice-Related Activation Changes in Schizophrenia

The present functional magnetic resonance imaging study investigated the neural correlates of practice-associated activation changes in patients with schizophrenia and their association with symptom severity. A group of patients (n = 24) were divided into more successful and less successful learners and were asked to perform a verbal overlearning task in the scanner. We found that both patient groups profited from practice, showing significant decreases in mean response times as well as significant learning-related decreases in cerebral activation. Direct comparison between groups yielded a relative hyperactivation in the group of the less successful learners at the beginning of practice, which showed a reduction with increasing practice. This was reflected by relatively stronger signal decreases in a predominantly fronto-parieto-cerebellar network. In the group of less successful learners, there was a negative correlation between general symptom scores and learning-related signal decreases in a task-relevant network involving cerebellar, inferior and middle frontal (BA 45/47, 46), superior parietal (BA 31), and superior temporal (BA 39) regions. Present data indicate that hyperactivity under high task demands might serve to identify those patients with less potential to profit from practice. However, at least in the context of moderate- to low-working memory demands, this activation abnormality seems to constitute a state rather than a trait characteristic, which patients manage to reduce by successful short-term learning. The findings also suggest that successful learners can better compensate potentially interfering effects exerted by disorder-related psychopathology.

The development of working memory: fMRI measures of frontal lobe contribution

Event Abstract Back to Event The development of working memory: fMRI measures of frontal lobe contribution M. Arsalidou1, L. Dade1, 2, S. Y. Lin1, 3* and M. J. Taylor1, 3, 4 1 Hospital for Sick Children, Diagnostic Imaging and Research Institute, Canada 2 Bloorview Research Institute, Canada 3 University of Toronto, Institute of Medical Science, Canada 4 University of Toronto, Department of Psychology, Canada Although working memory (WM) has been extensively studied in adults using fMRI, less is known about how this capacity develops. We assessed the neural correlates of WM in 39 children (6-16 years) and 18 adults (20-34 years), using an n-back, block design, fMRI paradigm. Colourful abstract patterns were presented in three conditions that varied by WM load (n = 0, 1 or 2). Using random effects ANOVA, we computed three contrasts (1>0, 2>0, 2>1) for participants who had > 80% accuracy. Adults responded to higher loads by increased activation of middle and inferior frontal regions. Older children (12-16 years) demonstrated some incremental frontal recruitment with WM load, but to a smaller extent than adults. Younger children (6-11 years) showed increased frontal activations for 1-back greater than both 0-back and 2-back. Thus, WM loads elicited age-related differential activity patterns. Given similar performance levels, differences in brain responses suggest that younger children employed different strategies, likely related to task difficulty and to immature frontal lobe function. Although the use of cognitive resources appeared more adult-like for older than younger children, the data demonstrate that significant maturational change is still occurring in the teenage years. Conference: The 20th Annual Rotman Research Institute Conference, The frontal lobes, Toronto, Canada, 22 Mar - 26 Mar, 2010. Presentation Type: Poster Presentation Topic: Frontal Lobe Development Citation: Arsalidou M, Dade L, Lin SY and Taylor MJ (2010). The development of working memory: fMRI measures of frontal lobe contribution. Conference Abstract: The 20th Annual Rotman Research Institute Conference, The frontal lobes. doi: 10.3389/conf.fnins.2010.14.00066 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Jun 2010; Published Online: 28 Jun 2010. * Correspondence: S. Y Lin, Hospital for Sick Children, Diagnostic Imaging and Research Institute, Toronto, Canada, sarah.yaolin@sickkids.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers M. Arsalidou L. Dade S. Y Lin M. J Taylor Google M. Arsalidou L. Dade S. Y Lin M. J Taylor Google Scholar M. Arsalidou L. Dade S. Y Lin M. J Taylor PubMed M. Arsalidou L. Dade S. Y Lin M. J Taylor Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

FMRI activation differences between 11-year-old good and poor spellers' access in working memory to temporary and long-term orthographic representations

Two fMRI task contrasts identified BOLD activation differences between good and poor 11-year-old spellers. On the first contrast comparing judgments about letters in unfamiliar orthographic representations (pseudowords) no longer displayed versus displayed (at the time of judgement), good and poor spellers differed in left posterior cingulate and calcarine and bilateral precuneus; fMRI activation correlated with real-word reading rate in good spellers and with composition in poor spellers. On the second contrast comparing judgments about whether both items in a pair pronounced the same were both correctly spelled real words and whether both letter strings matched exactly, good spellers activated more than poor writers in the left precentral gyrus, postcentral gyrus, and inferior frontral gyrus, and right superior frontal gyrus, but poor writers activated more than good writers in left primary motor and superior and middle frontal, and word form, and right cuneus and middle frontal regions; fMRI activation in 7 regions correlated with spelling achievement. Results have implications for how both temporary orthographic representations of unfamiliar written words and long-term, precise representations of familiar, learned words contribute to middle-childhood spelling acquisition.

Overlap in Frontotemporal Atrophy Between Normal Aging and Patients With Frontotemporal Dementias

Normal aging leads to frontocortical atrophy. The degree to which this complicates the use of frontotemporal atrophy as a diagnostic criterion for the frontotemporal dementias (FTDs) has not been reported. The present case-control study compared frontotemporal volumes delineated with semi-automatic brain region extraction [n=30 controls vs. 16 behavioral variant FTD (bvFTD) vs. 14 primary progressive aphasia]. Logistic regression identified those regions least helpful for distinguishing bvFTD and primary progressive aphasia from controls. Linear regression tested the correlation of duration of illness to atrophy severity. The control group showed high variance in volumes. Controls had right frontal lobe volumes that overlapped considerably with bvFTD volumes, but, as anticipated, the left anterior temporal volumes of interest showed 91% accuracy in distinguishing the aphasic subgroup from controls. Left-sided and not right-sided atrophy in the medial middle frontal region distinguished the bvFTD group from controls. The relegation of structural imaging to a supportive criterion for diagnosis is reasonable in the context of the range of atrophy due to normal aging. While volumetry identified left-sided atrophy as useful for identifying FTD cases, future studies should determine whether clinicians could make these distinctions on viewing routine diagnostic magnetic resonance imaging scans.

Fronto-temporal Interactions during Overt Verbal Initiation and Suppression

The Hayling Sentence Completion Task (HSCT) is known to activate left hemisphere frontal and temporal language regions. However, the effective connectivity between frontal and temporal language regions associated with the task has yet to be examined. The aims of the study were to examine activation and effective connectivity during the HSCT using a functional magnetic resonance imaging (fMRI) paradigm in which participants made overt verbal responses. We predicted that producing an incongruent response (response suppression), compared to a congruent one (response initiation), would be associated with greater activation in the left prefrontal cortex and an increase in the effective connectivity between temporal and frontal regions. Fifteen participants were scanned while completing 80 sentence stems. The congruency and constraint of sentences varied across trials. Dynamic Causal Modeling (DCM) and Bayesian Model Selection (BMS) were used to compare a set of alternative DCMs of fronto-temporal connectivity. The HSCT activated regions in the left temporal and prefrontal cortices, and the cuneus. Response suppression was associated with greater activation in the left middle and orbital frontal gyri and the bilateral precuneus than response initiation. Left middle temporal and frontal regions identified by the conventional fMRI analyses were entered into the DCM analysis. Using a systematic BMS procedure, the optimal DCM showed that the connection from the left middle temporal gyrus, which was driven by verbal stimuli per se, was significantly increased in strength during response suppression compared to initiation. Greater effective connectivity between left temporal and prefrontal regions during response suppression may reflect the transfer of information from posterior temporal regions where semantic and lexical information is stored to prefrontal regions where it is manipulated in preparation for an appropriate response.

Cholinergic Enhancement Eliminates Modulation of Neural Activity by Task Difficulty in the Prefrontal Cortex during Working Memory

Previously, we demonstrated that enhancing cholinergic activity during a working memory (WM) task improves performance and reduces blood flow in the right anterior middle/superior frontal cortex, an area known to be important for WM. The purpose of this study was to evaluate the interaction between WM task demands and cholinergic enhancement on neural responses in the prefrontal cortex. Regional cerebral blood flow (rCBF) was measured using H(2)(15)O and positron emission tomography, as 10 young healthy volunteers performed a parametrically varied match-to-sample WM for faces task. For each item, a picture of a face was presented, followed by a delay (1, 6, 11, or 16 sec), then by the presentation of two faces. Subjects were instructed to identify which face they previously had seen. For control items, nonsense pictures were presented in the same spatial and temporal manner. All conditions were performed during an intravenous infusion of saline and physostigmine (1 mg/hr). Subjects were blind to the substance being infused. Reaction time increased significantly with WM delay, and physostigmine decreased reaction time across delay conditions. Significant task-related rCBF increases during saline infusion were seen in superior frontal, middle frontal, and inferior frontal regions, and the response magnitudes in the regions increased systematically with task difficulty. In all of these prefrontal regions, physostigmine administration significantly reduced rCBF during task, particularly at longer task delays, so that no correlation between task delay and rCBF was observed. In the ventral visual cortex, physostigmine increased rCBF at longer task delays in medial regions, and decreased rCBF over delay conditions in lateral cortical areas. These results indicate that, during cholinergic potentiation, brain activity in prefrontal regions is not modulated by increases in WM task demands, and lends further support to the hypothesis that cholinergic modulation enhances visual processing, making the task easier to perform, and thus, compensate for the need to recruit prefrontal cortical regions as task demands increase.

IMAGING STUDIES BRIDGING THE DOPAMINE AND GLUTAMATE HYPOTHESES OF SCHIZOPHRENIA

Individuals at clinical high risk (CHR) who progress to fully psychotic symptoms have been observed to show a steeper rate of cortical gray matter reduction compared with individuals without symptomatic progression and with healthy control subjects. Whether such changes reflect processes associated with the pathophysiology of schizophrenia or exposure to antipsychotic drugs is unknown.In this multisite study, 274 CHR cases, including 35 individuals who converted to psychosis, and 135 healthy comparison subjects were scanned with magnetic resonance imaging at baseline, 12-month follow-up, or the point of conversion for the subjects who developed fully psychotic symptoms.In a traveling subjects substudy, excellent reliability was observed for measures of cortical thickness and subcortical volumes. Controlling for multiple comparisons throughout the brain, CHR subjects who converted to psychosis showed a steeper rate of gray matter loss in the right superior frontal, middle frontal, and medial orbitofrontal cortical regions as well as a greater rate of expansion of the third ventricle compared with CHR subjects who did not convert to psychosis and healthy control subjects. Differential tissue loss was present in subjects who had not received antipsychotic medications during the interscan interval and was predicted by baseline levels of an aggregate measure of proinflammatory cytokines in plasma.These findings demonstrate that the brain changes are not explained by exposure to antipsychotic drugs but likely play a role in psychosis pathophysiology. Given that the cortical changes were more pronounced in subjects with briefer durations of prodromal symptoms, contributing factors may predominantly play a role in acute-onset forms of psychosis.

Frontal Hypoactivation on Functional Magnetic Resonance Imaging in Working Memory after Severe Diffuse Traumatic Brain Injury

Working memory is frequently impaired after traumatic brain injury (TBI). The present study aimed to investigate working memory deficits in patients with diffuse axonal injury and to determine the contribution of cerebral activation dysfunctions to them. Eighteen patients with severe TBI and 14 healthy controls matched for age and gender were included in the study. TBI patients were selected according to signs of diffuse axonal injury on computed tomography (CT) and without any evidence of focal lesions on MRI clinical examination. Functional magnetic resonance (fMRI) was used to assess brain activation during n-back tasks (0-, 2-, and 3-back). Compared to controls, the TBI group showed significant working memory impairment on the Digits Backwards (p=0.022) and Letter-Number Sequencing subtests from the WAIS-III (p<0.001) under the 2-back (p=0.008) and 3-back (p=0.017) conditions. Both groups engaged bilateral fronto-parietal regions known to be involved in working memory, although patients showed less cerebral activation than did controls. Decreased activation in TBI patients compared to controls was observed mainly in the right superior and middle frontal cortex. The correlation patterns differed between patients and controls: while the control group showed a negative correlation between performance and activation in prefrontal cortex (PFC), TBI patients presented a positive correlation in right parietal and left parahippocampus for the low and high working memory load, respectively. In conclusion, severe TBI patients with diffuse brain damage show a pattern of cerebral hypoactivation in the right middle and superior frontal regions during working memory tasks, and also present an impaired pattern of performance correlations.

A structural–functional basis for dyslexia in the cortex of Chinese readers

Developmental dyslexia is a neurobiologically based disorder that affects approximately 5-17% of school children and is characterized by a severe impairment in reading skill acquisition. For readers of alphabetic (e.g., English) languages, recent neuroimaging studies have demonstrated that dyslexia is associated with weak reading-related activity in left temporoparietal and occipitotemporal regions, and this activity difference may reflect reductions in gray matter volume in these areas. Here, we find different structural and functional abnormalities in dyslexic readers of Chinese, a nonalphabetic language. Compared with normally developing controls, children with impaired reading in logographic Chinese exhibited reduced gray matter volume in a left middle frontal gyrus region previously shown to be important for Chinese reading and writing. Using functional MRI to study language-related activation of cortical regions in dyslexics, we found reduced activation in this same left middle frontal gyrus region in Chinese dyslexics versus controls, and there was a significant correlation between gray matter volume and activation in the language task in this same area. By contrast, Chinese dyslexics did not show functional or structural (i.e., volumetric gray matter) differences from normal subjects in the more posterior brain systems that have been shown to be abnormal in alphabetic-language dyslexics. The results suggest that the structural and functional basis for dyslexia varies between alphabetic and nonalphabetic languages.

Structural neural correlates of impairments in social cognition in first episode psychosis

Several studies have demonstrated that patients with schizophrenia show impairments in social cognition and current evidence indicate that this deficit is associated with abnormal activity in specific brain regions. In addition to functional imaging studies, we believe that the identification of structural correlates of social cognitive processes may help to better understand the neural underpinnings of these specific skills. The main objective of this study was to investigate the relationship between gray matter density and social cognitive deficits in first episode of schizophrenia spectrum psychosis, using a comprehensive assessment that we previously demonstrated to be a highly sensitive measure of social cognitive deficits in this population. Thirty-eight patients with a first episode of psychosis participated in this study, and the Four Factor Test of Social Intelligence was used as a measure of social cognition. Social cognitive impairments in first episode psychosis were significantly correlated with reduced gray-matter density in the left middle frontal gyrus other regions within the mirror neuron system network (MSN), namely the right supplementary motor cortex, the left superior temporal gyrus and the left inferior parietal lobule. We concluded that structural abnormalities within the MSN may account for the social cognitive deficits present in some psychiatric disorders, such as schizophrenia.

Verbal Working Memory Dysfunction in Schizophrenia: An fMRI Investigation

Impaired processing of working memory information is one of the cognitive deficits seen in patients with schizophrenia. This study aims at corroborating the differences in the brain activities involved in the process of working memory between patients with schizophrenia and the controls. Twelve patients with schizophrenia and 11 controls participated in the study. Functional magnetic resonance imaging (fMRI) was used to assess cortical activities during the performance of a two-back verbal working memory paradigm using the Korean alphabet as mnemonic content. Group analysis revealed that inferior fontal, middle frontal, and superior temporal region showed decreased cortical activities in the patient group compared to those of the controls. This study showed a decreased activation in inferior fontal (BA 47), middle frontal (BA 6), and superior temporal (BA 22/38) neural networks from the patient group and confirmed the earlier findings on the impaired working memory of schizophrenic patients in the fMRI investigation.

Abnormal Superior Temporal Connectivity During Fear Perception in Schizophrenia

Patients with schizophrenia have difficulty in decoding facial affect. A study using event-related functional neuroimaging indicated that errors in fear detection in schizophrenia are associated with paradoxically higher activation in the amygdala and an associated network implicated in threat detection. Furthermore, this exaggerated activation to fearful faces correlated with severity of flat affect. These findings suggest that abnormal threat detection processing may reflect disruptions between nodes that comprise the affective appraisal circuit. Here we examined connectivity within this network by determining the pattern of intercorrelations among brain regions (regions of interest) significantly activated during fear identification in both healthy controls and patients using a novel procedure CORANOVA. This analysis tests differences in the interregional correlation strength between schizophrenia and healthy controls. Healthy subjects' task activation was principally characterized by robust correlations between medial structures like thalamus (THA) and amygdala (AMY) and middle frontal (MF), inferior frontal (IF), and prefrontal cortical (PFC) regions. In contrast, schizophrenia patients displayed no significant correlations between the medial regions and either MF or IF. Further, patients had significantly higher correlations between occipital lingual gyrus and superior temporal gyrus than healthy subjects. These between-group connectivity differences suggest that schizophrenia threat detection impairment may stem from abnormal stimulus integration. Such abnormal integration may disrupt the evaluation of threat within fronto-cortical regions.

Common brain regions underlying different arithmetic operations as revealed by conjunct fMRI–BOLD activation

The issue of how and where arithmetic operations are represented in the brain has been addressed in numerous studies. Lesion studies suggest that a network of different brain areas are involved in mental calculation. Neuroimaging studies have reported inferior parietal and lateral frontal activations during mental arithmetic using tasks of different complexities and using different operators (addition, subtraction, etc.). Indeed, it has been difficult to compare brain activation across studies because of the variety of different operators and different presentation modalities used. The present experiment examined fMRI–BOLD activity in participants during calculation tasks entailing different arithmetic operations – addition, subtraction, multiplication and division – of different complexities. Functional imaging data revealed a common activation pattern comprising right precuneus, left and right middle and superior frontal regions during all arithmetic operations. All other regional activations were operation specific and distributed in prominently frontal, parietal and central regions when contrasting complex and simple calculation tasks. The present results largely confirm former studies suggesting that activation patterns due to mental arithmetic appear to reflect a basic anatomical substrate of working memory, numerical knowledge and processing based on finger counting, and derived from a network originally related to finger movement. We emphasize that in mental arithmetic research different arithmetic operations should always be examined and discussed independently of each other in order to avoid invalid generalizations on arithmetics and involved brain areas.

Temporally Graded Activation of Neocortical Regions in Response to Memories of Different Ages

The temporally graded memory impairment seen in many neurobehavioral disorders implies different neuroanatomical pathways and/or cognitive mechanisms involved in storage and retrieval of memories of different ages. A dynamic interaction between medial-temporal and neocortical brain regions has been proposed to account for memory's greater permanence with time. Despite considerable debate concerning its time-dependent role in memory retrieval, medial-temporal lobe activity has been well studied. However, the relative participation of neocortical regions in recent and remote memory retrieval has received much less attention. Using functional magnetic resonance imaging, we demonstrate robust, temporally graded signal differences in posterior cingulate, right middle frontal, right fusiform, and left middle temporal regions in healthy older adults during famous name identification from two disparate time epochs. Importantly, no neocortical regions demonstrated greater response to older than to recent stimuli. Our results suggest a possible role of these neocortical regions in temporally dating items in memory and in establishing and maintaining memory traces throughout the lifespan. Theoretical implications of these findings for the two dominant models of remote memory functioning (Consolidation Theory and Multiple Trace Theory) are discussed.

Age‐related changes in reading systems of dyslexic children

To examine age-related changes in the neural systems for reading in nonimpaired and dyslexic children and adolescents. Functional magnetic resonance imaging was used to study age-related changes in the neural systems for reading in a cross-sectional sample of 232 right-handed children 7 to 18 years of age (113 dyslexic readers and 119 nonimpaired readers) as they read pseudowords. In nonimpaired readers, systems in the left anterior lateral occipitotemporal area developed with age, whereas systems in the right superior and middle frontal regions decreased. In contrast, in dyslexic readers, systems in the left posterior medial occipitotemporal regions developed with age. Older nonimpaired readers were left lateralized in the anterior lateral occipitotemporal area; there was no difference in asymmetry between younger and older dyslexic readers. These findings offer a possible neurobiological explanation for the differences in reading acquisition between dyslexic and nonimpaired readers and provide further evidence of the critical role of the left occipitotemporal region in the development of reading.

Contextual interference in recognition memory with age

Previous behavioral research suggests that although elderly adults' memory benefits from supportive context, misleading or irrelevant contexts produce greater interference. In the present study, we use event-related fMRI to investigate age differences when processing contextual information to make recognition judgments. Twenty-one young and twenty elderly incidentally encoded pictures of objects presented in meaningful contexts, and completed a memory test for the objects presented in identical or novel contexts. Elderly committed more false alarms than young when novel objects were presented in familiar, but task-irrelevant, contexts. Elderly showed reduced engagement of bilateral dorsolateral prefrontal cortex and anterior cingulate relative to young, reflecting disruption of a cognitive control network for processing context with age. Disruption occurred for both high and low-performing elderly, suggesting that cognitive control deficits are pervasive with age. Despite showing disruption of the cognitive control network, high-performing elderly recruited additional middle and medial frontal regions that were not recruited by either low-performing elderly or young adults. This suggests that high-performing elderly may compensate for the disruption of the cognitive control network by recruiting additional frontal resources to overcome cognitive control deficits that affect recognition memory.

Evidence for neural accommodation to a writing system following learning.

Native English speakers with no knowledge of Chinese were trained on 60 Chinese characters according to one of three mapping conditions: orthography to pronunciation and meaning (P + M), orthography to pronunciation (P), and orthography to meaning (M). Following the training, fMRI scans taken during passive viewing of Chinese characters showed activation in brain regions that partially overlap the regions found in studies of skilled Chinese readers, but typically not found in alphabetic readers. Areas include bilateral middle frontal (BA 9), right occipital (BA 18/19), and fusiform (BA 37) regions. The activation pattern of Chinese characters was similar across the three groups. However, peak location was different in the left middle frontal region between groups. Direct contrasts between the groups also revealed stronger activation of left middle frontal in the P + M group. The results suggest that learners acquired skill in reading Chinese characters using a brain network similar to that used by Chinese native speakers. The results are consistent with the system accommodation hypothesis: The brain's reading network accommodates to features of an acquired writing system.

Mild Cognitive Impairment after Lacunar Infarction: Voxel-Based Morphometry and Neuropsychological Assessment

Background: The aim of the present study was to investigate whether there were differences in neuroradiological features, including white-matter lesions and gray-matter volumes, between patients with lacunar infarction with and without mild cognitive impairment of the vascular type (MCI-V). Methods: A total of 40 patients with lacunar infarction were studied within 1 month after stroke. Results: MCI-V was found in 22 patients, who in comparison with patients without cognitive impairment were significantly older and had fewer years of formal education. MRI subcortical hyperintensities especially in the basal ganglia (putamen and thalamus) were significantly more frequent in the MCI-V group. In the voxel-based morphometric study, patients with MCI-V showed more atrophy bilaterally in the middle temporal gyrus, right and left frontal and posterior bilateral occipitoparietal regions including the posterior cingulate as well as in the cerebellum. A region of interest analysis restricted to the parahippocampi and hippocampi showed further reduced bilateral parahippocampal gyrus and right hippocampus volume reductions in this group of patients. Finally, the amount of white-matter lesions among MCI-V showed negative correlations with gray-matter volume in frontal and temporal areas as well as with the thalamus and mesencephalon. Conclusions: The present findings provide support for an anatomical substrate of the MCI entity in patients with lacunar infarction. Both gray- and white-matter changes seem to contribute to the cognitive impairment of such patients.

Patterns of Frontal Lobe Atrophy in Frontotemporal Dementia: A Volumetric MRI Study

Objectives: Frontotemporal dementia (FTD), the second commonest degenerative cause of dementia under the age of 65, often presents with striking changes in behaviour and personality in association with frontal lobe atrophy. Based on the behavioural changes observed in FTD, it is commonly assumed that the orbitofrontal cortex is the earliest and most severely affected frontal sub-region. However, evidence to support this assumption has to date been largely lacking. Methods: Using a novel volumetric MRI method, we performed a detailed volumetric analysis of six frontal regions in 12 subjects with the frontal or behavioural variant of FTD (fvFTD) and 12 age-, education- and sex-matched normal controls. The regions studied were: the orbitofrontal and insula regions (representing the orbitobasal cortex); the inferior and middle frontal regions (representing the dorsolateral prefrontal areas); and the superior frontal and anterior cingulate regions (representing the medial prefrontal areas). Results: As a group, the fvFTD patients showed atrophy involving all six regions. We then segregated the 12 patients into three sub-groups according to their overall degree of atrophy. In the mildest group (n = 3) all regions fell within 2 standard deviations of normal. In the intermediate group (n = 6) only the orbitofrontal region (bilaterally) fell clearly outside the control range (>2 z scores below the control mean); the next most atrophic region in this group was the right insular region. The severe group (n = 3) had generalized atrophy throughout the frontal regions measured. Conclusions: In conclusion, patients with the earliest stages of fvFTD show no significant loss of volume in any frontal lobe area as measured by a novel MRI volumetric technique. When volume loss does occur, changes are initially seen in the orbitofrontal cortex before atrophy becomes more widespread. These results provide some partial support for the often-quoted assumption that the orbitofrontal cortex is the locus of earliest pathology in fvFTD, although these findings must be regarded as preliminary in view of the small numbers of patients involved.

Partially enhanced thalamocortical functional connectivity in autism

Based on evidence for thalamic abnormalities in autism, impairments of thalamocortical pathways have been suspected. We examined the functional connectivity between thalamus and cerebral cortex in terms of blood oxygen level dependent (BOLD) signal cross-correlation in 8 male participants with high-functioning autism and matched normal controls, using functional MRI during simple visuomotor coordination. Both groups exhibited widespread connectivity, consistent with known extensive thalamocortical connectivity. In a direct group comparison, overall more extensive connectivity was observed in the autism group, especially in the left insula and in right postcentral and middle frontal regions. Our findings are inconsistent with the hypothesis of general underconnectivity in autism and instead suggest that subcortico-cortical connectivity may be hyperfunctional, potentially compensating for reduced cortico-cortical connectivity.