Anterior Temporal Lobe Regions Research Articles

Socioemotional Dysfunction From Temporal Lobe Involvement in Frontotemporal Dementia: A Preliminary Report.

Socioemotional changes, rather than cognitive impairments, are the feature that defines behavioral variant frontotemporal dementia (bvFTD). Investigators have attributed the socioemotional changes in bvFTD and other dementias to frontal lobe dysfunction; however, recent work implies a further contribution from right anterior temporal disease. The authors evaluated relationships between regional brain atrophy and socioemotional changes in both bvFTD and early-onset Alzheimer's disease (EOAD). This study explored the neuroanatomical correlations of performance on the Socioemotional Dysfunction Scale (SDS), an instrument previously shown to document socioemotional changes in bvFTD, among 13 patients with bvFTD not preselected for anterior temporal involvement and 16 age-matched patients with early-onset Alzheimer's disease (EOAD). SDS scores were correlated with volumes of regions of interest assessed with tensor-based morphometric analysis of MRI images. As expected, the bvFTD group had significantly higher SDS scores overall and smaller frontal regions compared with the EOAD group, which in turn had smaller volumes in temporoparietal regions. SDS scores significantly correlated with lateral anterior temporal lobe (ATL) atrophy, and a regression analysis that controlled for diagnosis indicated that SDS scores predicted lateral ATL volume. Within the bvFTD group, higher SDS scores were associated with smaller lateral and right ATL regions, as well as a smaller orbitofrontal cortex. Within the EOAD group, higher SDS scores were associated with a smaller right parietal cortex. This study confirms that, in addition to orbitofrontal disease, there is a prominent right and lateral ATL origin of socioemotional changes in bvFTD and further suggests that right parietal involvement contributes to socioemotional changes in EOAD.

Hierarchical organization of the human ventral visual streams revealed with magnetoencephalography.

The hierarchical organization between 25 ventral stream visual cortical regions and 180 cortical regions was measured with magnetoencephalography using the Human Connectome Project Multimodal Parcellation atlas in 83 Human Connectome Project participants performing a visual memory task. The aim was to reveal the hierarchical organization using a whole-brain model based on generative effective connectivity with this fast neuroimaging method. V1-V4 formed a first group of interconnected regions. Especially V4 had connectivity to a ventrolateral visual stream: V8, the fusiform face cortex, and posterior inferior temporal cortex PIT. These regions in turn had effectivity connectivity to inferior temporal cortex visual regions TE2p and TE1p. TE2p and TE1p then have connectivity to anterior temporal lobe regions TE1a, TE1m, TE2a, and TGv, which are multimodal. In a ventromedial visual stream, V1-V4 connect to ventromedial regions VMV1-3 and VVC. VMV1-3 and VVC connect to the medial parahippocampal gyrus PHA1-3, which, with the VMV regions, include the parahippocampal scene area. The medial parahippocampal PHA1-3 regions have connectivity to the hippocampal system regions the perirhinal cortex, entorhinal cortex, and hippocampus. These effective connectivities of two ventral visual cortical streams measured with magnetoencephalography provide support to the hierarchical organization of brain systems measured with fMRI, and new evidence on directionality.

The endoscopic anterior transmaxillary temporal pole approach for mesial temporal lobe epilepsies: a feasibility study.

In mesial temporal lobe epilepsy (MTLE), the ideal surgical approach to achieve seizure freedom and minimize morbidity is an unsolved question. Selective approaches to mesial temporal structures often result in suboptimal seizure outcomes. The authors report the results of a pilot study intended to evaluate the clinical feasibility of using an endoscopic anterior transmaxillary (eATM) approach for minimally invasive management of MTLEs. The study is a prospectively collected case series of four consecutive patients who underwent the eATM approach for the treatment of MTLE and were followed for a minimum of 12 months. All participants underwent an epilepsy workup and surgical care at a tertiary referral comprehensive epilepsy center and had medically refractory epilepsy. The noninvasive evaluations and intracranial recordings of these patients confirmed the presence of anatomically restricted epileptogenic zones located in the mesial temporal structures. Data on seizure freedom at 1 year, neuropsychological outcomes, diffusion tractography, and adverse events were collected and analyzed. By applying the eATM technique and approaching the far anterior temporal lobe regions, mesial-basal resections of the temporal polar areas and mesial temporal structures were successfully achieved in all patients (2 with left-sided approaches, 2 with right-sided approaches). No neurological complications or neuropsychological declines were observed. All 4 patients achieved Engel class Ia outcome up to the end of the follow-up period (19, 15, 14, and 12 months). One patient developed hypoesthesia in the left V2 distribution but there were no other adverse events. The low degree of white matter injury from the eATM approach was analyzed using high-definition fiber tractography in 1 patient as a putative mechanism for preserving neuropsychological function. The described series demonstrates the feasibility and potential safety profile of a novel approach for medically refractory MTLE. The study affirms the feasibility of performing efficacious mesial temporal lobe resections through an eATM approach.

The role of the ventrolateral anterior temporal lobes in social cognition.

A key challenge for neurobiological models of social cognition is to elucidate whether brain regions are specialised for that domain. In recent years, discussion surrounding the role of anterior temporal regions epitomises such debates; some argue the anterior temporal lobe (ATL) is part of a domain‐specific network for social processing, while others claim it comprises a domain‐general hub for semantic representation. In the present study, we used ATL‐optimised fMRI to map the contribution of different ATL structures to a variety of paradigms frequently used to probe a crucial social ability, namely ‘theory of mind’ (ToM). Using multiple tasks enables a clearer attribution of activation to ToM as opposed to idiosyncratic features of stimuli. Further, we directly explored whether these same structures are also activated by a non‐social task probing semantic representations. We revealed that common to all of the tasks was activation of a key ventrolateral ATL region that is often invisible to standard fMRI. This constitutes novel evidence in support of the view that the ventrolateral ATL contributes to social cognition via a domain‐general role in semantic processing and against claims of a specialised social function.

Anomia is present pre-symptomatically in frontotemporal dementia due to MAPT mutations

IntroductionA third of frontotemporal dementia (FTD) is caused by an autosomal-dominant genetic mutation in one of three genes: microtubule-associated protein tau (MAPT), chromosome 9 open reading frame 72 (C9orf72) and progranulin (GRN). Prior studies of prodromal FTD have identified impaired executive function and social cognition early in the disease but few have studied naming in detail.MethodsWe investigated performance on the Boston Naming Test (BNT) in the GENetic Frontotemporal dementia Initiative cohort of 499 mutation carriers and 248 mutation-negative controls divided across three genetic groups: C9orf72, MAPT and GRN. Mutation carriers were further divided into 3 groups according to their global CDR plus NACC FTLD score: 0 (asymptomatic), 0.5 (prodromal) and 1 + (fully symptomatic). Groups were compared using a bootstrapped linear regression model, adjusting for age, sex, language and education. Finally, we identified neural correlates of anomia within carriers of each genetic group using a voxel-based morphometry analysis.ResultsAll symptomatic groups performed worse on the BNT than controls with the MAPT symptomatic group scoring the worst. Furthermore, MAPT asymptomatic and prodromal groups performed significantly worse than controls. Correlates of anomia in MAPT mutation carriers included bilateral anterior temporal lobe regions and the anterior insula. Similar bilateral anterior temporal lobe involvement was seen in C9orf72 mutation carriers as well as more widespread left frontal atrophy. In GRN mutation carriers, neural correlates were limited to the left hemisphere, and involved frontal, temporal, insula and striatal regions.ConclusionThis study suggests the development of early anomia in MAPT mutation carriers, likely to be associated with impaired semantic knowledge. Clinical trials focused on the prodromal period within individuals with MAPT mutations should use language tasks, such as the BNT for patient stratification and as outcome measures.

Intracerebral electrical stimulation of the right anterior fusiform gyrus impairs human face identity recognition

Brain regions located between the right fusiform face area (FFA) in the middle fusiform gyrus and the temporal pole may play a critical role in human face identity recognition but their investigation is limited by a large signal drop-out in functional magnetic resonance imaging (fMRI). Here we report an original case who is suddenly unable to recognize the identity of faces when electrically stimulated on a focal location inside this intermediate region of the right anterior fusiform gyrus. The reliable transient identity recognition deficit occurs without any change of percept, even during nonverbal face tasks (i.e., pointing out the famous face picture among three options; matching pictures of unfamiliar or familiar faces for their identities), and without difficulty at recognizing visual objects or famous written names. The effective contact is associated with the largest frequency-tagged electrophysiological signals of face-selectivity and of familiar and unfamiliar face identity recognition. This extensive multimodal investigation points to the right anterior fusiform gyrus as a critical hub of the human cortical face network, between posterior ventral occipito-temporal face-selective regions directly connected to low-level visual cortex, the medial temporal lobe involved in generic memory encoding, and ventral anterior temporal lobe regions holding semantic associations to people's identity.

Electrophysiological abnormalities as indicators of early-stage pathology in Primary Progressive Aphasia (PPA): A case study in semantic variant PPA

ABSTRACT Language induced and spontaneous oscillatory activity was measured using MEG in a patient with the semantic variant of Primary Progressive Aphasia (svPPA) and 15 healthy controls.The patient showed oscillatory slowing in the left anterior temporal lobe (ATL) that extended into non-atrophied brain tissue in left and right frontal areas. The white matter connections were reduced to the left and right ATL and left frontal regions, exhibiting electrophysiological abnormalities. Altered diffusion metrics in all four language tracts, indicted compromised white matter integrity. Task-related and spontaneous oscillatory abnormalities can indicate early neurodegeneration in svPPA, providing promising targets for intervention.

Differential regulation of excitatory synaptic transmission in the hippocampus and anterior temporal lobe by cyclin dependent kinase 5 (Cdk5) in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS)

Mesial temporal lobe epilepsy with hippocamapal sclerosis (MTLE-HS) is the most common form of drug resistant epilepsy (DRE). MTLE-HS is a distributed network disorder comprising of not only the hippocampus, but other anatomically related extrahippocampal regions. Excitatory synaptic transmission is differentially regulated in the hippocampal and extra-hippocampal regions of patients with MTLE-HS, but its mechanism not understood. Cyclin-dependent kinase 5 (Cdk5) is known to regulate synaptic transmission and plasticity through up-regulation of NMDA receptors by phosphorylating NR2Asubunits. The present study is designed to investigate whether Cdk5 differentially regulates the excitatory synaptic transmission in the hippocampus and anterior temporal lobe (ATL) samples obtained from patients of MTLE-HS. We have measured the Cdk5 kinase activity and the protein levels of Cdk5, p-Cdk5, p35/p25, NR2A, pNR2A in the hippocampal and ATL samples obtained from patients with MTLE-HS. We have also determined the effect of roscovitine, a Cdk5 antagonist, on spontaneous excitatory postsynaptic currents (EPSCs) recorded from the hippocampal and ATL using patch-clamp technique. We observed significant increase in the expression of Cdk5, p-Cdk5, p35/p25, NR2A, pNR2A in the ATL samples as compared to the hippocampal samples. Cdk5 activity was significantly higher in ATL samples as compared to the hippocampal samples. Magnitude of reduction in the frequency of EPSCs by roscovitine in the ATL samples was higher than that in the hippocampal samples. Our studies suggest that Cdk5 differentially regulates excitatory synaptic activity in the hippocampal and ATL region of patients with MTLE-HS.

Neural mechanisms of predicting individual preferences based on group membership.

Successful social interaction requires humans to predict others’ behavior. To do so, internal models of others are generated based on previous observations. When predicting others’ preferences for objects, for example, observations are made at an individual level (5-year-old Rosie often chooses a pencil) or at a group level (kids often choose pencils). But previous research has focused either on already established group knowledge, i.e. stereotypes, or on the neural correlates of predicting traits and preferences of individuals. We identified the neural mechanisms underlying predicting individual behavior based on learned group knowledge using fMRI. We show that applying learned group knowledge hinges on both a network of regions commonly referred to as the mentalizing network, and a network of regions implicated in representing social knowledge. Additionally, we provide evidence for the presence of a gradient in the posterior temporal cortex and the medial frontal cortex, catering to different functions while applying learned group knowledge. This process is characterized by an increased connectivity between medial prefrontal cortex and other mentalizing network regions and increased connectivity between anterior temporal lobe and other social knowledge regions. Our study provides insights into the neural mechanisms underlying the application of learned group knowledge.

Dynamic activity patterns in the anterior temporal lobe represents object semantics

ABSTRACT The anterior temporal lobe (ATL) is considered a crucial area for the representation of transmodal concepts. Recent evidence suggests that specific regions within the ATL support the representation of individual object concepts, as shown by studies combining multivariate analysis methods and explicit measures of semantic knowledge. This research looks to further our understanding by probing conceptual representations at a spatially and temporally resolved neural scale. Representational similarity analysis was applied to human intracranial recordings from anatomically defined lateral to medial ATL sub-regions. Neural similarity patterns were tested against semantic similarity measures, where semantic similarity was defined by a hybrid corpus-based and feature-based approach. Analyses show that the perirhinal cortex, in the medial ATL, significantly related to semantic effects around 200 to 400 ms, and were greater than more lateral ATL regions. Further, semantic effects were present in low frequency (theta and alpha) oscillatory phase signals. These results provide converging support that more medial regions of the ATL support the representation of basic-level visual object concepts within the first 400 ms, and provide a bridge between prior fMRI and MEG work by offering detailed evidence for the presence of conceptual representations within the ATL.

Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology

Post-mortem studies show that focal anterior temporal lobe (ATL) neurodegeneration is most often caused by frontotemporal lobar degeneration TDP-43 type C pathology. Clinically, these patients are described with different terms, such as semantic variant primary progressive aphasia (svPPA), semantic dementia (SD), or right temporal variant frontotemporal dementia (FTD) depending on whether the predominant symptoms affect language, semantic knowledge for object or people, or socio-emotional behaviors. ATL atrophy presents with various degrees of lateralization, with right-sided cases considered rarer even though estimation of their prevalence is hampered by the paucity of studies on well-characterized, pathology-proven cohorts. Moreover, it is not clear whether left and right variants show a similar distribution of atrophy within the ATL cross-sectionally and longitudinally.Here we study the largest cohort to-date of pathology-proven TDP-43-C cases diagnosed during life as svPPA, SD or right temporal variant FTD. We analyzed clinical, cognitive, and neuroimaging data from 30 cases, a subset of which was followed longitudinally. Guided by recent structural and functional parcellation studies, we constructed four bilateral ATL regions of interest (ROIs). The computation of an atrophy lateralization index allowed the comparison of atrophy patterns between the two hemispheres. This led to an automatic, imaging-based classification of the cases as left-predominant or right-predominant. We then compared the two groups in terms of regional atrophy patterns within the ATL ROIs (cross-sectionally) and atrophy progression (longitudinally).Results showed that 40% of pathology proven cases of TDP-43-C diagnosed with a temporal variant presented with right-lateralized atrophy. Moreover, the findings of our ATL ROI analysis indicated that, irrespective of atrophy lateralization, atrophy distribution within both ATLs follows a medial-to-lateral gradient. Finally, in both left and right cases, atrophy appeared to progress to the contralateral ATL, and from the anterior temporal pole to posterior temporal and orbitofrontal regions.Taken together, our findings indicate that incipient right predominant ATL atrophy is common in TDP-43-C pathology, and that distribution of damage within the ATLs appears to be the same in left- and right- sided variants. Thus, regardless of differences in clinical phenotype and atrophy lateralization, both temporal variants of FTD should be viewed as a spectrum presentation of the same disease.

Verbal semantics and the left dorsolateral anterior temporal lobe: a longitudinal case of bilateral temporal degeneration

ABSTRACT Background Semantic variant primary progressive aphasia (svPPA), a clinical syndrome characterized by loss of semantic knowledge, is associated with neurodegeneration that starts in the anterior temporal lobe (ATL) and gradually spreads towards posterior temporal and medial frontal areas. At the earliest stages, atrophy may be predominantly lateralized to either the left or right ATL, leading to different clinical profiles with the greatest impairment of word comprehension or visual/social semantics, respectively. Methods & Procedures We report the in-depth longitudinal investigation of cognitive and neuroanatomical features of JB, an unusual case of ATL neurodegeneration with relative sparing of left lateral ATL regions. Outcomes & Results Over the course of 9 years, neurodegeneration progressed to involve bilateral temporo-lateral and frontal regions, resulting in a relatively symmetric and diffuse frontotemporal atrophy pattern. In parallel, JB developed greater behavioral, cognitive, and language impairments, as well as signs of motor neuron disease at her last evaluation. Episodic memory and socio-emotional processing deficits arose, likely secondary to semantic verbal deficits, while visuospatial processing, executive function, and non-semantic language abilities remained largely unaffected throughout the course of the disease. Conclusions The details of this rare case of early medial more than lateral ATL degeneration are consistent with a bilateral organization of the semantic system and, crucially, with a functional dissociation between medial paralimbic and lateral neocortical temporal regions. Cases of frontotemporal dementia (FTD) such as JB, who initially do not meet current clinical criteria for svPPA and instead present with some features of behavioral variant FTD, highlight the need for specific criteria for the right temporal variant of FTD that we propose could be called semantic variant FTD.

Close yet independent: Dissociation of social from valence and abstract semantic dimensions in the left anterior temporal lobe.

The anterior temporal lobe (ATL) is engaged in various types of semantic dimensions. One consistently reported dimension is social information, with abstract words describing social behaviors inducing stronger activations in the ATL than nonsocial words. One potential factor that has been systematically confounded in this finding is emotional valence, given that abstract social words tend to be associated with emotional feelings. We investigated which factors drove the ATL sensitivity using a 2 (social/nonsocial) × 2 (valenced/neutral) factorial design in an fMRI study with relatively high spatial resolutions. We found that sociality and valence were processed in different ATL regions without significant interactions: The social effect was found in the left anterior superior temporal sulcus (aSTS), whereas the valence effect activated small clusters in the bilateral temporal poles (TP). In the left ATL, the social- and valence-related clusters were distinct from another superior ATL area that exhibited a general "abstractness" effect with little modulation of sociality or valence. These subregions exhibited distinct whole-brain functional connectivity patterns during the resting state, with the social cluster functionally connected to the default mode network, the valence cluster connected to the adjacent temporal regions and amygdala, and the abstractness cluster connected to a distributed network including a set of language-related regions. These results of activation profiles and connectivity patterns together indicate that the way in which the left ATL supports semantic processing is highly fine-grained, with the neural substrate for social semantic effects dissociated from those for emotional valence and abstractness.

A MEG study of the neural substrates of semantic processing in semantic variant primary progressive aphasia

ABSTRACTDespite a well-documented pattern of semantic impairment, the patterns of brain activation during semantic processing in semantic variant primary progressive aphasia (svPPA) still remain poorly understood. In the current study, one svPPA patient (EC) and six elderly controls carried out a general-level semantic categorization task while their brain activity was recorded using magnetoencephalography (MEG). Despite similar behavioral performance, EC showed hyperactivation of the left inferior temporal gyrus (ITG) and right anterior temporal lobe (ATL) relative to controls. This suggests that periatrophic regions within the ATL region may support preserved semantic abilities in svPPA.

016 One disease or three: is frontotemporal dementia – motor neuron disease a distinct entity?

IntroductionFrontotemporal dementia-motor neuron disease (FTD-MND) is diagnosed when patients meet criteria for the diagnosis of both FTD and MND, but the mode presentation of this disorder is currently unknown. This study aimed to compare the mode of presentation, and profiles of behavioural and language disturbances, of FTD-MND with that of other FTD phenotypes using a data-driven approach.Methods31 FTD-MND, 119 bvFTD, 47 PNFA, 42 SD patients and 127 controls underwent comprehensive clinical, neuropsychological and neuroimaging assessments. Z-transformed scores were used to compare the severity of behavioural and language domains in each disease group. Two-step cluster analysis profiled patient subgroups. Voxel-based morphometry investigated differential patterns of cortical atrophy between groups.ResultsOverall, FTD-MND patients presented with behavioural or language disturbances less frequently than FTD phenotypes, but mixed behavioural-language presentations were more common. FTD-MND patients demonstrated less severe disinhibition, apathy and semantic deficits relative to bvFTD and SD respectively.Behavioural and language deficits were of comparable severity in FTD-MND, unlike other FTD phenotypes where behaviour was worse than language (bvFTD) or language worse than behaviour (PNFA, SD).In cluster analysis, FTD-MND patients were evenly distributed across three subgroups designated as ‘mild mixed’, ‘language dominant’ and ‘behavioural dominant’. Relative to the ‘mild mixed’ group, ‘language dominant’ patients demonstarted more atrophy of the anterior temporal lobe and peri-insular regions, while ‘behavioural dominant’ patients displayed more prefrontal atrophy.ConclusionFTD-MND does not present as a uniform syndrome. Rather, there may be at least three subgroups that demonstrate distinctive cognitive, behavioural, and neuroanatomical characteristics.

Left temporal lobe language network connectivity in temporal lobe epilepsy.

Impairment of naming function is a critical problem for temporal lobe epilepsy patients, yet the neural correlates of the disruption of temporal lobe language networks are poorly understood. Using functional MRI, we investigated the activation and task-related functional connectivity of left temporal lobe language networks and their relation to clinical naming performance and disease characteristics. We studied 59 adult patients with temporal lobe epilepsy (35 left temporal lobe epilepsy) and 32 healthy controls with auditory and visual naming functional MRI tasks. Time series of activation maxima in the left posterior inferior temporal lobe were extracted to create a psychophysiological interaction regressor for subsequent seed-based whole-brain task-related functional connectivity analyses. Correlational analyses were performed to assess the association of functional MRI activation and functional connectivity with clinical naming scores, age of onset of epilepsy, and duration of epilepsy. Auditory naming elicited activation in the left posterior inferior temporal gyrus and visual naming in the left fusiform gyrus across all groups. Activations in the left inferior temporal gyrus, left thalamus and left supplementary motor region during auditory naming as well as left fusiform activations during picture naming correlated with better clinical naming performance. Functional connectivity analyses indicated coupling of left posterior inferior temporal regions to bilateral anterior and posterior temporal lobe regions and the bilateral inferior precentral gyrus as well as contralateral occipital cortex. Stronger functional connectivity was associated with better clinical naming performance in all groups. In patients with left temporal lobe epilepsy only, functional connectivity increased with later age of onset of epilepsy and shorter disease duration. This suggests that onset of seizures early in life and prolonged disease duration lead to disrupted recruitment of temporal lobe networks ipsilateral to the seizure focus, which might account for naming deficits in temporal lobe epilepsy.

Memory Dysfunction.

This article reviews the current understanding of memory system anatomy and physiology, as well as relevant evaluation methods and pathologic processes. Our understanding of memory formation advances each year. Successful episodic memory formation depends not only on intact medial temporal lobe structures but also on well-orchestrated interactions with other large-scale brain networks that support executive and semantic processing functions. Recent discoveries of cognitive control networks have helped in understanding the interaction between memory systems and executive systems. These interactions allow access to past experiences and enable comparisons between past experiences and external and internal information. The semantic memory system is less clearly defined anatomically. Anterior, lateral, and inferior temporal lobe regions appear to play a crucial role in the function of the semantic processing system. Different but tightly interconnected cortical regions, such as the prefrontal region, may play a controlling role in this system. The presentation of clinical disease affecting memory is the result of the selective vulnerability of the memory system. An understanding of current concepts of memory anatomy, physiology, and evaluation plays a central role in establishing an accurate diagnosis. Different memory systems rely on separate but overlapping distributed brain networks. Certain pathologic processes preferentially affect memory systems. An understanding of memory formation stages will enable more accurate diagnosis.

The Neurobiology of Agrammatic Sentence Comprehension: A Lesion Study.

Broca's area has long been implicated in sentence comprehension. Damage to this region is thought to be the central source of "agrammatic comprehension" in which performance is substantially worse (and near chance) on sentences with noncanonical word orders compared with canonical word order sentences (in English). This claim is supported by functional neuroimaging studies demonstrating greater activation in Broca's area for noncanonical versus canonical sentences. However, functional neuroimaging studies also have frequently implicated the anterior temporal lobe (ATL) in sentence processing more broadly, and recent lesion-symptom mapping studies have implicated the ATL and mid temporal regions in agrammatic comprehension. This study investigates these seemingly conflicting findings in 66 left-hemisphere patients with chronic focal cerebral damage. Patients completed two sentence comprehension measures, sentence-picture matching and plausibility judgments. Patients with damage including Broca's area (but excluding the temporal lobe; n = 11) on average did not exhibit the expected agrammatic comprehension pattern-for example, their performance was >80% on noncanonical sentences in the sentence-picture matching task. Patients with ATL damage ( n = 18) also did not exhibit an agrammatic comprehension pattern. Across our entire patient sample, the lesions of patients with agrammatic comprehension patterns in either task had maximal overlap in posterior superior temporal and inferior parietal regions. Using voxel-based lesion-symptom mapping, we find that lower performances on canonical and noncanonical sentences in each task are both associated with damage to a large left superior temporal-inferior parietal network including portions of the ATL, but not Broca's area. Notably, however, response bias in plausibility judgments was significantly associated with damage to inferior frontal cortex, including gray and white matter in Broca's area, suggesting that the contribution of Broca's area to sentence comprehension may be related to task-related cognitive demands.

Frontotemporal lobar degeneration and social behaviour: Dissociation between the knowledge of its consequences and its conceptual meaning

Inappropriate social behaviour is an early symptom of frontotemporal lobar degeneration (FTLD) in both behavioural variant frontotemporal dementia (bvFTD) and semantic dementia (SD) subtypes. Knowledge of social behaviour is essential for appropriate social conduct. The superior anterior temporal lobe (ATL) has been identified as one key neural component for the conceptual knowledge of social behaviour, but it is unknown whether this is dissociable from knowledge of the consequences of social behaviour. Here, we used a newly-developed test of knowledge about long-term and short-term consequences of social behaviour to investigate its impairment in patients with FTLD relative to a previously-developed test of social conceptual knowledge. We included 19 healthy elderly control participants and 19 consecutive patients with features of bvFTD or SD and defined dissociations as performance differences between tasks for each patient (Bonferroni-corrected p < .05). Knowledge of long-term consequences was selectively impaired relative to short-term consequences in five patients and the reverse dissociation occurred in one patient. Six patients showed a selective impairment of social concepts relative to long-term consequences with the reverse dissociation occurring in one patient. These results corroborate the hypothesis that knowledge of long-term consequences of social behaviour is dissociable from knowledge of short-term consequences, as well as of social conceptual knowledge. Confirming our hypothesis, we found that patients with more marked grey matter (GM) volume loss in frontopolar relative to right superior ATL regions of interest exhibited poorer knowledge of the long-term consequences of social behaviour relative to the knowledge of its conceptual meaning and vice versa (n = 15). These findings support the hypothesis that frontopolar and ATL regions represent distinct aspects of social knowledge. This suggests that rather than being unable to suppress urges to behave inappropriately, FTLD patients often lose the knowledge of what appropriate social behaviour is and can therefore not be expected to behave accordingly.

Dissociable patterns of brain activity for mentalizing about known others: a role for attachment.

The human brain tracks dynamic changes within the social environment, forming and updating representations of individuals in our social milieu. This mechanism of social navigation builds an increasingly complex map of persons with whom we are familiar and form attachments to guide adaptive social behaviors. We examined the neural representation of known others along a continuum of attachment using fMRI. Heterosexual adults (N = 29, 16 females), in romantic relationships for more than 2 years, made trait judgments for a romantic partner, parent, close friend, familiar acquaintance and self-during scanning. Multivariate analysis, partial least squares, was used to identify whole-brain patterns of brain activation associated with trait judgments of known others across a continuum of attachment. Across conditions, trait judgments engaged the default network and lateral prefrontal cortex. Judgments about oneself and a partner were associated with a common activation pattern encompassing anterior and middle cingulate, posterior superior temporal sulcus, as well as anterior insula. Parent and close friend judgments engaged medial and anterior temporal lobe regions. These results provide novel evidence that mentalizing about known familiar others results in differential brain activity. We provide initial evidence that the representation of adult attachment is a distinguishing feature of these differences.