Research on language and aging typically shows that language comprehension is preserved across the life span. Recent neuroimaging results suggest that this good performance is underpinned by age-related neural reorganization [e.g., Tyler, L. K., Shafto, M. A., Randall, B., Wright, P., Marslen-Wilson, W. D., & Stamatakis, E. A. Preserving syntactic processing across the adult life span: The modulation of the frontotemporal language system in the context of age-related atrophy. Cerebral Cortex, 20, 352–364, 2010]. The current study examines how age-related reorganization affects the balance between component linguistic processes by manipulating semantic and phonological factors during spoken word recognition in younger and older adults. Participants in an fMRI study performed an auditory lexical decision task where words varied in their phonological and semantic properties as measured by degree of phonological competition and imageability. Older adults had a preserved lexicality effect, but compared with younger people, their behavioral sensitivity to phonological competition was reduced, as was competition-related activity in left inferior frontal gyrus. This was accompanied by increases in behavioral sensitivity to imageability and imageability-related activity in left middle temporal gyrus. These results support previous findings that neural compensation underpins preserved comprehension in aging and demonstrate that neural reorganization can affect the balance between semantic and phonological processing.
The core of human language, which differentiates it from the communicative abilities of other species, is the set of combinatorial operations called syntax. For over a century researchers have attempted to understand how this essential function is organised in the brain. Here we combine behavioural and neuroimaging methods, with left hemisphere-damaged patients and healthy controls, to identify the pathways connecting the brain regions involved in syntactic processing. In a previous fMRI study (Tyler et al. 2010b) we established that regions of left inferior frontal cortex and left posterior middle temporal cortex were activated during syntactic processing. These clusters were used here as seeds for probabilistic tractography analyses in patients and controls, allowing us to delineate, and measure the integrity of, the white matter tracts connecting the frontal and temporal regions active for syntax. We found that structural disconnection in either of two fibre bundles - the arcuate fasciculus or the extreme capsule fibre system - was associated with syntactic impairment in patients. The results demonstrate the causal role in syntactic analysis of these two major left hemisphere fibre bundles - challenging existing views about their role in language functions, and providing a new basis for future research in this key area of human cognition.
diffusion tensor imaging; connectivity; tractography; stroke; grammar
Understanding the relationship between brain and cognition critically depends on data from brain-damaged patients since these provide major constraints on identifying the essential components of brain–behavior systems. Here we relate structural and functional fMRI data with behavioral data in 21 human patients with chronic left hemisphere (LH) lesions and a range of language impairments to investigate the controversial issue of the role of the hemispheres in different language functions. We address this issue within a dual neurocognitive model of spoken language comprehension in which core linguistic functions, e.g., syntax, depend critically upon an intact left frontotemporal system, whereas more general communicative abilities, e.g., semantics, are supported by a bilateral frontotemporal system and may recover from LH damage through normal or enhanced activity in the intact right hemisphere. The fMRI study used a word-monitoring task that differentiated syntactic and semantic aspects of sentence comprehension. We distinguished overlapping interactions between structure, neural activity, and performance using joint independent components analysis, identifying two structural–functional networks, each with a distinct relationship with performance. Syntactic performance correlated with tissue integrity and activity in a left frontotemporal network. Semantic performance correlated with activity in right superior/middle temporal gyri regardless of tissue integrity. Right temporal activity did not differ between patients and controls, suggesting that the semantic network is degenerately organized, with regions in both hemispheres able to perform similar computations. Our findings support the dual neurocognitive model of spoken language comprehension and emphasize the importance of linguistic specificity in investigations of language recovery in patients.
The production and comprehension of human language is thought to involve a network of frontal, parietal, and temporal cortical loci interconnected by two dominant white matter pathways. These two white matter bundles, often referred to as the dorsal and ventral processing tracts, are hypothesized to have markedly different language functions. The dorsal tract is thought to process phonological processing, while the ventral tract is considered to abet semantics. This proposed functional differentiation of tracts is similar to the ventral and dorsal dichotomy proposed for the visual and auditory systems. The present study evaluated this characterization of the language system in the context of various components involved in its function. Twenty-four chronic stroke patients completed a battery of 10 language tests designed to measure performance on the comprehension and production of phonology, morphology, semantics, and syntax. The patients also completed diffusion MRI scanning. Lesions were confined to the left hemisphere, but the size and location of the insult varied so that patients had damage to a single tract, both tracts, or neither tract. Individual FA maps were generated, and focal areas of hypointensity served as markers of white matter damage. Whole-brain voxel-by-voxel correlations revealed that only phonological and semantic tasks fit into the dual-stream model, while syntax and morphology involved both pathways. ROI analyses of the arcuate fascicle and extreme capsule supported this finding. These data suggest that natural language function is more likely to reflect a synergistic system rather than a segregated dual-stream system.
In the current event-related potential (ERP) study, we investigated how speech rhythm impacts speech segmentation and facilitates the resolution of syntactic ambiguities in auditory sentence processing. Participants listened to syntactically ambiguous German subject- and object-first sentences that were spoken with either regular or irregular speech rhythm. Rhythmicity was established by a constant metric pattern of three unstressed syllables between two stressed ones that created rhythmic groups of constant size. Accuracy rates in a comprehension task revealed that participants understood rhythmically regular sentences better than rhythmically irregular ones. Furthermore, the mean amplitude of the P600 component was reduced in response to object-first sentences only when embedded in rhythmically regular but not rhythmically irregular context. This P600 reduction indicates facilitated processing of sentence structure possibly due to a decrease in processing costs for the less-preferred structure (object-first). Our data suggest an early and continuous use of rhythm by the syntactic parser and support language processing models assuming an interactive and incremental use of linguistic information during language processing.
C-reactive protein (CRP) is associated with the risk of cardiovascular disease (CVD); whether the effects are modified by diabetes status still is unclear. This study investigated these issues and assessed the added value of CRP to predictions.
RESEARCH DESIGN AND METHODS
Participants were drawn from representative samples of adults living in England and Scotland. Cox proportional hazards regression models were used to relate baseline plasma CRP with all-cause and CVD mortality during follow-up in men and women with and without diabetes. The added value of CRP to the predictions was assessed through c-statistic comparison and relative integrated discrimination improvement.
A total of 25,979 participants (4.9% with diabetes) were followed for a median of 93 months, during which period there were 2,767 deaths (957 from CVD). CRP (per SD loge) was associated with a 53% (95% CI 43–64) and 43% (38–49) higher risk of cardiovascular and all-cause mortality, respectively. These associations were log linear and did not differ according to diabetes status (both P ≥ 0.08 for interaction), sex, and other risk factors. Adding CRP to conventional risk factors improved predictions overall and separately by diabetes status but not for CVD mortality, although such improvements only were marginal based on several discrimination statistics.
The association between CRP and CVD was similar across diabetes status, and the effects are broadly similar across levels of other conventional risk factors.
Prospective studies report associations between indicators of time spent sitting and obesity risk. Most studies use a single indicator of sedentary behavior and are unable to clearly identify whether sedentary behavior is a cause or a consequence of obesity.
To investigate cross-sectional and prospective associations between multiple sitting time indicators and obesity and examine the possibility of reverse causality.
Using data from the Whitehall II cohort, multiple logistic models were fitted to examine associations between prevalent obesity (BMI ≥30) at Phase 5 (1997–1999), and incident obesity between Phases 5 and 7 (2003–2004) across four levels of five sitting exposures (work sitting, TV viewing, non-TV leisure-time sitting, leisure-time sitting, and total sitting). Using obesity data from three prior phases (1985–1988, 1991–1993; and recalled weight at age 25 years), linear regression models were fitted to examine the association between prior obesity and sitting time at Phase 5. Analyses were conducted in 2012.
None of the sitting exposures were associated with obesity either cross-sectionally or prospectively. Obesity at one previous measurement phase was associated with a 2.43-hour/week (95% CI=0.07, 4.78) increase in TV viewing; obesity at three previous phases was associated with a 7.42-hour/week (95% CI=2.7, 12.46) increase in TV-viewing hours/week at Phase 5.
Sitting time was not associated with obesity cross-sectionally or prospectively. Prior obesity was prospectively associated with time spent watching TV per week but not other types of sitting.
The neural efficiency hypothesis postulates an inverse relationship between intelligence and brain activation. Previous research suggests that gender and task modality represent two important moderators of the neural efficiency phenomenon. Since most of the existing studies on neural efficiency have used ERD in the EEG as a measure of brain activation, the central aim of this study was a more detailed analysis of this phenomenon by means of functional MRI. A sample of 20 males and 20 females, who had been screened for their visuo-spatial intelligence, was confronted with a mental rotation task employing an event-related approach. Results suggest that less intelligent individuals show a stronger deactivation of parts of the default mode network, as compared to more intelligent people. Furthermore, we found evidence of an interaction between task difficulty, intelligence and gender, indicating that more intelligent females show an increase in brain activation with an increase in task difficulty. These findings may contribute to a better understanding of the neural efficiency hypothesis, and possibly also of gender differences in the visuo-spatial domain.
In a natural setting, speech is often accompanied by gestures. As language, speech-accompanying iconic gestures to some extent convey semantic information. However, if comprehension of the information contained in both the auditory and visual modality depends on same or different brain-networks is quite unknown. In this fMRI study, we aimed at identifying the cortical areas engaged in supramodal processing of semantic information. BOLD changes were recorded in 18 healthy right-handed male subjects watching video clips showing an actor who either performed speech (S, acoustic) or gestures (G, visual) in more (+) or less (−) meaningful varieties. In the experimental conditions familiar speech or isolated iconic gestures were presented; during the visual control condition the volunteers watched meaningless gestures (G−), while during the acoustic control condition a foreign language was presented (S−). The conjunction of the visual and acoustic semantic processing revealed activations extending from the left inferior frontal gyrus to the precentral gyrus, and included bilateral posterior temporal regions. We conclude that proclaiming this frontotemporal network the brain's core language system is to take too narrow a view. Our results rather indicate that these regions constitute a supramodal semantic processing network.
Cognitive processing slows with age. We sought to determine the importance of white matter integrity, assessed by diffusion tensor imaging (DTI), at influencing cognitive processing speed among normal older adults, assessed using a novel battery of computerized, non-verbal, choice reaction time tasks. We studied 131 cognitively normal adults aged 55–87 using a cross-sectional design. Each participant underwent our test battery, as well as MRI with DTI. We carried out cross-subject comparisons using tract-based spatial statistics. As expected, reaction time slowed significantly with age. In diffuse areas of frontal and parietal white matter, especially the anterior corpus callosum, fractional anisotropy values correlated negatively with reaction time. The genu and body of the corpus callosum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus were among the areas most involved. This relationship was not explained by gray or white matter atrophy or by white matter lesion volume. In a statistical mediation analysis, loss of white matter integrity mediated the relationship between age and cognitive processing speed.
At one level “sustained attention” is simply a description of a task demand. It is often used, however, in reference to a putatively unitary capacity to remain engaged in tasks that are lengthy, dull, repetitive and/or characterised by long intervals between relevant events. Deficits in sustained attention have been reported in a range of clinical conditions. Despite this, there is paucity of well-controlled human functional imaging evidence about regions commonly recruited during diverse sustained attention tasks. Here, for the first time, we used functional magnetic resonance imaging (fMRI) to monitor brain activity patterns as healthy volunteers performed two sustained attention tasks. The first, widely used in clinical assessment, required participants to count tones separated by long unpredictable intervals. This was contrasted with a control counting condition in which tones were presented at a brisk, regular rate. The second task was the Sustained Attention to Response Test (SART) in which participants responded to sequentially presented digits with the exception of a nominated infrequent no-go target. In the control condition, no-go trials were explicitly absent, removing the requirement to maintain a readiness to withhold responses. Although there were distinct patterns of activation associated with each task relative to its control, activity common to both tasks was found in the bilateral inferior frontal operculum, anterior cingulate, and bilateral premotor cortex. Although some researchers argue for a specific role of the inferior frontal operculum in inhibition, our results are consistent with recent findings of a more general attentional role for this area. The maintenance of a goal directed stance in the absence of strong environmental facilitation is challenging and this may underpin the sensitivity of sustained attention tasks to functional difficulties in a range of clinical groups.
The E4 allele of the ApoE gene has consistently been shown to be related to an increased risk of Alzheimer's disease (AD). The E4 allele is also associated with functional and structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess volumes of deep grey matter structures of 22 healthy younger ApoE4 carriers and 22 non-carriers (20–38 years). Volumes of the nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen, thalamus and brain stem were calculated by FMRIB's Integrated Registration and Segmentation Tool (FIRST) algorithm. A significant drop in volume was found in the right hippocampus of ApoE4 carriers (ApoE4+) relative to non-carriers (ApoE4−), while there was a borderline significant decrease in the volume of the left hippocampus of ApoE4 carriers. The volumes of no other structures were found to be significantly affected by genotype. Atrophy has been found to be a sensitive marker of neurodegenerative changes, and our results show that within a healthy young population, the presence of the ApoE4+ carrier gene leads to volume reduction in a structure that is vitally important for memory formation. Our results suggest that the hippocampus may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age. Although volume reductions were noted bilaterally in the hippocampus, atrophy was more pronounced in the right hippocampus. This finding relates to previous work which has noted a compensatory increase in right hemisphere activity in ApoE4 carriers in response to preclinical declines in memory function. Possession of the ApoE4 allele may lead to greater predilection for right hemisphere atrophy even in healthy young subjects in their twenties.
We sought to use a regional homogeneity (ReHo) approach as an index in resting-state functional magnetic resonance imaging (fMRI) to investigate the features of spontaneous brain activity within the default mode network (DMN) in patients suffering from bipolar depression (BD).
Twenty-six patients with BD and 26 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans. We compared the differences in ReHo between the two groups within the DMN and investigated the relationships between sex, age, years of education, disease duration, the Hamilton Rating Scale for Depression (HAMD) total score, and ReHo in regions with significant group differences.
Our results revealed that bipolar depressed patients had increased ReHo in the left medial frontal gyrus and left inferior parietal lobe compared to healthy controls. No correlations were found between regional ReHo values and sex, age, and clinical features within the BD group.
Our findings indicate that abnormal brain activity is mainly distributed within prefrontal-limbic circuits, which are believed to be involved in the pathophysiological mechanisms underlying bipolar depression.
The ability to accurately perceive emotions is crucial for effective social interaction. Many questions remain regarding how different sources of emotional cues in speech (e.g., prosody, semantic information) are processed during emotional communication. Using a cross-modal emotional priming paradigm (Facial affect decision task), we compared the relative contributions of processing utterances with single-channel (prosody-only) versus multi-channel (prosody and semantic) cues on the perception of happy, sad, and angry emotional expressions. Our data show that emotional speech cues produce robust congruency effects on decisions about an emotionally related face target, although no processing advantage occurred when prime stimuli contained multi-channel as opposed to single-channel speech cues. Our data suggest that utterances with prosodic cues alone and utterances with combined prosody and semantic cues both activate knowledge that leads to emotional congruency (priming) effects, but that the convergence of these two information sources does not always heighten access to this knowledge during emotional speech processing.
It is widely accepted that the perception of human voices is supported by neural structures located along the superior temporal sulci. However, there is an ongoing discussion to what extent the activations found in fMRI studies are evoked by the vocal features themselves or are the result of phonetic processing. To show that the temporal lobes are indeed engaged in voice processing, short utterances spoken by famous and unknown people were presented to healthy young participants whose task it was to identify the familiar speakers. In two event-related fMRI experiments, the temporal lobes were found to differentiate between familiar and unfamiliar voices such that named voices elicited higher BOLD signal intensities than unfamiliar voices. Yet, the temporal cortices did not only discriminate between familiar and unfamiliar voices. Experiment 2, which required overtly spoken responses and allowed to distinguish between four familiarity grades, revealed that there was a fine-grained differentiation between all of these familiarity levels with higher familiarity being associated with larger BOLD signal amplitudes. Finally, we observed a gradual response change such that the BOLD signal differences between unfamiliar and highly familiar voices increased with the distance of an area from the transverse temporal gyri, especially towards the anterior temporal cortex and the middle temporal gyri. Therefore, the results suggest that (the anterior and non-superior portions of) the temporal lobes participate in voice-specific processing independent from phonetic components also involved in spoken speech material.
The aim of the present volumetric study was to explore the neuro-anatomical correlates of autobiographical memory loss in Alzheimer's patients and healthy elderly, in terms of the delay of retention, with a particular interest in the medial temporal lobe structures. Fifteen patients in early stages of the disease and 11 matched control subjects were included in the study. To assess autobiographical memory and the effect of the retention delay, a modified version of the Crovitz test was used according to five periods of life. Autobiographical memory deficits were correlated to local atrophy via structural MRI using Voxel Based Morphometry. We used a ‘lateralized index’ to compare the relative contribution of hippocampal sub-regions (anterior vs posterior, left vs right) according to the different periods of life. Our results confirm the involvement of the hippocampus proper in autobiographical memory retrieval for both recent and very remote encoding periods, with larger aspect for the very remote period on the left side. Contrary to the prominent left-sided involvement for the young adulthood period, the implication of the right hippocampus prevails for the more recent periods and decreases with the remotness of the memories, which might be associated with the visuo-spatial processing of the memories. Finally, we suggest the existence of a rostrocaudal gradient depending on the retention duration, with left anterior aspects specifically related to retrieval deficits of remote memories from the young adulthood period, whereas posterior aspects would result of simultaneous encoding and/or consolidation and retrieval deficit of more recent memories.
The dual-route model of speech processing includes a dorsal stream that maps auditory to motor features at the sublexical level rather than at the lexico-semantic level. However, the literature on gesture is an invitation to revise this model because it suggests that the premotor cortex of the dorsal route is a major site of lexico-semantic interaction. Here we investigated lexico-semantic mapping using word-gesture pairs that were either congruent or incongruent. Using fMRI-adaptation in 28 subjects, we found that temporo-parietal and premotor activity during auditory processing of single action words was modulated by the prior audiovisual context in which the words had been repeated. The BOLD signal was suppressed following repetition of the auditory word alone, and further suppressed following repetition of the word accompanied by a congruent gesture (e.g. [“grasp” + grasping gesture]). Conversely, repetition suppression was not observed when the same action word was accompanied by an incongruent gesture (e.g. [“grasp” + sprinkle]). We propose a simple model to explain these results: auditory and visual information converge onto premotor cortex where it is represented in a comparable format to determine (in)congruence between speech and gesture. This ability of the dorsal route to detect audiovisual semantic (in)congruence suggests that its function is not restricted to the sublexical level.
Task selection, previously thought to operate only under conscious, voluntary control, can be activated by unconsciously-perceived stimuli. In most cases, such activation is observed for unconscious stimuli that closely resemble other conscious, task-relevant stimuli and hence may simply reflect perceptual activation of consciously established stimulus-task associations. However, other studies have reported ‘direct’ unconscious-stimulus influences on task selection in the absence of any conscious, voluntary association between that stimulus and task (e.g., Zhou and Davis, 2012). In new experiments, described here, these latter influences on cued- and free-choice task selection appear robust and long-lived, yet, paradoxically, are suppressed to undetectable levels following momentary conscious prime-task pairing. Assessing, and rejecting, three intuitive explanations for such suppressive effects, we conclude that conscious prime-task pairing minimizes non-strategic influences of unconscious stimuli on task selection, insulating endogenous choice mechanisms from maladaptive external control.
Consistent resting brain activity patterns have been repeatedly demonstrated using measures derived from resting BOLD fMRI data. While those metrics are presumed to reflect underlying spontaneous brain activity (SBA), it is challenging to prove that association because resting BOLD fMRI metrics are purely model-free and scale-free variables. Cerebral blood flow (CBF) is typically closely coupled to brain metabolism and is used as a surrogate marker for quantifying regional brain function, including resting function. Assessing the correlations between resting BOLD fMRI measures and CBF correlation should provide a means of linking of those measures to the underlying SBA, and a means to quantify those scale-free measures. The purpose of this paper was to examine the CBF correlations of 3 widely used neuroimaging-based SBA measures, including seed-region based functional connectivity (FC), regional homogeneity (ReHo), and amplitude of low frequency fluctuation (ALFF). Test-retest data were acquired to check the stability of potential correlations across time. Reproducible posterior cingulate cortex (PCC) FC vs regional CBF correlations were found in much of the default mode network and visual cortex. Dorsal anterior cingulate cortex (ACC) FC vs CBF correlations were consistently found in bilateral prefrontal cortex. Both ReHo and ALFF were found to be reliably correlated with CBF in most of brain cortex. None of the assessed SBA measures was correlated with whole brain mean CBF. These findings suggest that resting BOLD fMRI-derived measures are coupled with regional CBF and are therefore linked to regional SBA.
Little is known about psychological risk factors in cerebrovascular disease. We examined the association between psychological distress and risk of death due to cerebrovascular disease.
We obtained data from 68 652 adult participants of the Health Survey for England (mean age 54.9 [standard deviation 13.9] yr, 45.0% male sex) with no known history of cardiovascular diseases at baseline. We used the 12-item General Health Questionnaire (GHQ-12) to assess the presence of psychological distress. We followed participants for eight years for cause-specific death using linkage to national registers.
There were 2367 deaths due to cardiovascular disease during follow-up. Relative to participants with no symptoms of psychological distress (GHQ-12 score 0) at baseline, people with psychological distress (GHQ-12 score ≥ 4, 14.7% of participants) had an increased risk of death from cerebrovascular disease (adjusted hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.32–2.08) and ischemic heart disease (adjusted HR 1.59, 95% CI 1.34–1.88). There was also evidence of a dose–response effect with increasing GHQ-12 score (p for trend < 0.001 in all analyses). Associations were only marginally attenuated after we adjusted for possible confounders, including socioeconomic status, smoking and use of antihypertensive medications.
Psychological distress was associated with increased risk of death due to cerebrovascular disease in a large population-representative cohort. These data suggest that the cardiovascular effects of psychological distress are not limited to coronary artery disease.
Age-related variations in resting state connectivity of the human brain were examined from young adulthood through middle age. A voxel-based network measure, degree, was used to assess age-related differences in tissue connectivity throughout the brain. Increases in connectivity with age were found in paralimbic cortical and subcortical regions. Decreases in connectivity were found in cortical regions, including visual areas and the default mode network. These findings differ from those of recent developmental studies examining earlier growth trajectories, and are consistent with known changes in cognitive function and emotional processing during mature aging. The results support and extend previous findings that relied on a priori definitions of regions of interest for their analyses. This approach of applying a voxel-based measure to examine the functional connectivity of individual tissue elements over time, without the need for a priori region of interest definitions, provides an important new tool in brain science.
Extensive research shows that inter-talker variability (i.e., changing the talker) affects recognition memory for speech signals. However, relatively little is known about the consequences of intra-talker variability (i.e. changes in speaking style within a talker) on the encoding of speech signals in memory. It is well established that speakers can modulate the characteristics of their own speech and produce a listener-oriented, intelligibility-enhancing speaking style in response to communication demands (e.g., when speaking to listeners with hearing impairment or non-native speakers of the language). Here we conducted two experiments to examine the role of speaking style variation in spoken language processing. First, we examined the extent to which clear speech provided benefits in challenging listening environments (i.e. speech-in-noise). Second, we compared recognition memory for sentences produced in conversational and clear speaking styles. In both experiments, semantically normal and anomalous sentences were included to investigate the role of higher-level linguistic information in the processing of speaking style variability. The results show that acoustic-phonetic modifications implemented in listener-oriented speech lead to improved speech recognition in challenging listening conditions and, crucially, to a substantial enhancement in recognition memory for sentences.
There is increasing evidence that amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) lie on a clinical, pathological and genetic continuum with patients of one disease exhibiting features of the other. Nevertheless, to date, the underlying grey matter and white matter changes across the ALS-FTD disease continuum have not been explored. In this study fifty-three participants with ALS (n = 10), ALS-FTD (n = 10) and behavioural variant FTD (bvFTD; n = 15) as well as controls (n = 18), underwent detailed clinical assessment plus structural imaging using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis of magnetic resonance brain imaging to examine grey and white matter differences and commonalities across the continuum. Importantly, patient groups were matched for age, education, gender and disease duration. VBM and DTI results showed that changes in the ALS group were confined mainly to the motor cortex and anterior cingulate as well as their underlying white matter tracts. ALS-FTD and bvFTD showed widespread grey matter and white matter changes involving frontal and temporal lobes. Extensive prefrontal cortex changes emerged as a marker for bvFTD compared to other subtypes, while ALS-FTD could be distinguished from ALS by additional temporal lobe grey and white matter changes. Finally, ALS could be mainly distinguished from the other two groups by corticospinal tract degeneration. The present study shows for the first time that FTD and ALS overlap in anterior cingulate, motor cortex and related white matter tract changes across the whole continuum. Nevertheless, frontal and temporal atrophy as well as corticospinal tract degeneration emerged as marker for subtype classification, which will inform future diagnosis and target disease management across the continuum.