Anterior Temporal Lobe Atrophy Research Articles

Anterior temporal lobe is necessary for efficient lateralised processing of spoken word identity

In the healthy human brain, the processing of language is strongly lateralised, usually to the left hemisphere, while the processing of complex non-linguistic sounds recruits brain regions bilaterally. Here we asked whether the anterior temporal lobes, strongly implicated in semantic processing, are critical to this special treatment of spoken words. Nine patients with semantic dementia (SD) and fourteen age-matched controls underwent magnetoencephalography and structural MRI. Voxel based morphometry demonstrated the stereotypical pattern of SD: severe grey matter loss restricted to the anterior temporal lobes, with the left side more affected. During magnetoencephalography, participants listened to word sets in which identity and meaning were ambiguous until word completion, for example PLAYED versus PLATE. Whereas left-hemispheric responses were similar across groups, patients demonstrated increased right hemisphere activity 174–294 msec after stimulus disambiguation. Source reconstructions confirmed recruitment of right-sided analogues of language regions in SD: atrophy of anterior temporal lobes was associated with increased activity in right temporal pole, middle temporal gyrus, inferior frontal gyrus and supramarginal gyrus. Overall, the results indicate that anterior temporal lobes are necessary for normal and efficient lateralised processing of word identity by the language network.

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.

Magnetic resonance imaging brain atrophy assessment in primary age-related tauopathy (PART)

Alzheimer disease (AD) is a neurodegenerative disorder characterized pathologically by the accumulation of amyloid-beta (Aβ) plaques and tau neurofibrillary tangles (NFTs). Recently, primary age-related tauopathy (PART) has been described as a new anatomopathological disorder where NFTs are the main feature in the absence of neuritic plaques. However, since PART has mainly been studied in post-mortem patient brains, not much is known about the clinical or neuroimaging characteristics of PART. Here, we studied the clinical brain imaging characteristics of PART focusing on neuroanatomical vulnerability by applying a previously validated multiregion visual atrophy scale. We analysed 26 cases with confirmed PART with paired clinical magnetic resonance imaging (MRI) acquisitions. In this selected cohort we found that upon correcting for the effect of age, there is increased atrophy in the medial temporal region with increasing Braak staging (r = 0.3937, p = 0.0466). Upon controlling for Braak staging effect, predominantly two regions, anterior temporal (r = 0.3638, p = 0.0677) and medial temporal (r = 0.3836, p = 0.053), show a trend for increased atrophy with increasing age. Moreover, anterior temporal lobe atrophy was associated with decreased semantic memory/language (r = − 0.5823, p = 0.0056; and r = − 0.6371, p = 0.0019, respectively), as was medial temporal lobe atrophy (r = − 0.4445, p = 0.0435). Overall, these findings support that PART is associated with medial temporal lobe atrophy and predominantly affects semantic memory/language. These findings highlight that other factors associated with aging and beyond NFTs could be involved in PART pathophysiology.

A Case of a Monolingual Spanish-Speaking Latina with Semantic Variant Primary Progressive Aphasia (svPPA)

Abstract Objective Often, individuals with lower educational attainment and limited proficiency in the English language get misdiagnosed and/or undertreated, which can impact their quality of life and other outcomes. The present case study intends to review and discuss the presentation of a monolingual, Spanish-speaking woman with Semantic Variant Primary Progressive Aphasia (svPPA), who was originally referred for a neuropsychological evaluation to determine the severity of her existing Alzheimer’s Disease (AD) diagnosis. Case Description Ms. X, is a 64-year-old, right-handed Hispanic woman with 6 years of education. Symptoms included forgetfulness, restlessness, and insomnia. Her family reported that she was repeating her ideas frequently during conversations and failing to recognize previously acquainted people, including her own relatives. A recent MRI of the brain showed anterior temporal lobe atrophy. Diagnostic Impressions and Outcomes Overall, she showed naming deficits (anomia), impaired verbal fluency, surface dyslexia, and significant problems with comprehension. Executive functioning, sentence repetition, working memory, and attention were generally intact. Qualitatively, her speech was apparently fluent and automatic, yet clearly empty in meaning. In Ms. X’s case, collateral reports of word-finding difficulties, tendency to repeat her thoughts incessantly, associative agnosia and prosopagnosia, and spared repetition and motor speech are strongly indicative of svPPA. Discussion svPPA primarily impacts language production and comprehension, and is characterized by severe anomia, word-finding difficulties, impaired single word comprehension, and in some cases, defective recognition of familiar faces. On testing, impairments can be observed in confrontation naming, with motor speech and repetition, working memory, episodic memory, visuospatial skills, and problem-solving skills relatively intact. Language symptoms are thought to stem from deficits of the semantic system.

Naming and conceptual understanding in frontotemporal dementia

Behavioural variant frontotemporal dementia (bvFTD) is characterised by behaviour change and impaired executive skills. There is growing evidence that naming difficulties may also be present but the basis for these is unclear. A primary semantic deficit has been proposed, although executive contributions to naming breakdown are also possible. The study aimed to improve understanding of the naming disorder in bvFTD through direct comparison with semantic dementia (SD), and examination of neural correlates. It aimed also to address current controversies about the role of the anterior temporal lobes in semantic memory. We studied 71 bvFTD and 32 SD patients. Naming data were elicited by two picture naming tests (one challenging and one less demanding) and word comprehension by word-picture matching. Structural magnetic resonance images were rated blind using a standardised visual rating scale. Around half of bvFTD patients showed impaired naming and 17% impaired word-picture matching. Deficits in bvFTD were less severe than in SD, but showed a similar pattern. There were strong inverse correlations between naming scores and atrophy in temporal structures, particularly temporal pole and fusiform gyrus. Word comprehension scores correlated more strongly with posterior than anterior temporal lobe atrophy in SD. Error analysis highlighted a significant relationship in both groups between associative-type responses and temporal pole atrophy. By contrast, ‘don't know’ responses, suggesting a loss of conceptual knowledge, correlated with more posterior temporal regions. There was some correlation in bvFTD between naming and executive test performance but not with frontal lobe atrophy. The findings support the view that naming problems can arise in bvFTD independently of patients' ‘frontal’ executive impairment and highlight clinical overlap between bvFTD and SD. We discuss the findings in relation to the hub and spoke model of semantic memory and argue against the notion of an anterior temporal lobe semantic hub.

Gray matter predictors of treatment outcomes in semantic variant primary progressive aphasia

Gray matter predictors of treatment outcomes in semantic variant primary progressive aphasia

Neural encoding of phonetic features relates to phonological processing in PPA

Neural encoding of phonetic features relates to phonological processing in PPA

Semantic dementia and the left and right temporal lobes

Semantic dementia, a circumscribed disorder of semantic knowledge, provides a unique model for understanding the neural basis for semantic representation. The study addressed areas of contention: the relative roles of the left and right temporal lobe, the contribution of anterior versus posterior temporal cortex and the status of the anterior temporal lobes as amodal hub. Naming and word comprehension was examined in 41 semantic dementia patients, 31 with left-predominant and 10 right-predominant atrophy. In keeping with expectation, naming and comprehension were significantly poorer in left-predominant patients. Structural magnetic resonance image analysis, using a visual rating scale, showed strong inverse correlations between naming scores and severity of both left anterior and posterior temporal lobe atrophy. By contrast, comprehension performance was more strongly correlated with left posterior temporal atrophy. Analysis of naming errors revealed a correlation between anterior temporal atrophy and associative/functional descriptive responses, implying availability of semantic information. By contrast, ‘don't know’ responses, indicative of loss of semantic knowledge, were linked to left posterior temporal lobe atrophy. Semantic errors, the hallmark of semantic dementia, were linked to right hemisphere atrophy, especially the right posterior temporal lobe. Matched visual-verbal tasks (famous face and name identification, Pyramids and Palm trees pictures and words, animal knowledge from 3-D models and animal names) administered to nine patients elicited variable correspondence between performance on nonverbal and verbal versions of the task. Marked performance dissociations were demonstrated in some patients: poorer understanding of names/words in left-predominant patients and of faces/pictures/models in right-predominant cases. The findings are compatible with the notion of the anterior temporal lobes as areas of convergence, but are less easily accommodated within the framework of amodal conceptual representation. The data, which reconcile some apparent contradictions in the literature, are discussed in the light of the nature and distribution of degenerative change in semantic dementia.

Semantic word category processing in semantic dementia and posterior cortical atrophy

There is general agreement that perisylvian language cortex plays a major role in lexical and semantic processing; but the contribution of additional, more widespread, brain areas in the processing of different semantic word categories remains controversial. We investigated word processing in two groups of patients whose neurodegenerative diseases preferentially affect specific parts of the brain, to determine whether their performance would vary as a function of semantic categories proposed to recruit those brain regions. Cohorts with (i) Semantic Dementia (SD), who have anterior temporal-lobe atrophy, and (ii) Posterior Cortical Atrophy (PCA), who have predominantly parieto-occipital atrophy, performed a lexical decision test on words from five different lexico-semantic categories: colour (e.g., yellow), form (oval), number (seven), spatial prepositions (under) and function words (also). Sets of pseudo-word foils matched the target words in length and bi-/tri-gram frequency. Word-frequency was matched between the two visual word categories (colour and form) and across the three other categories (number, prepositions, and function words). Age-matched healthy individuals served as controls. Although broad word processing deficits were apparent in both patient groups, the deficit was strongest for colour words in SD and for spatial prepositions in PCA. The patterns of performance on the lexical decision task demonstrate (a) general lexicosemantic processing deficits in both groups, though more prominent in SD than in PCA, and (b) differential involvement of anterior-temporal and posterior-parietal cortex in the processing of specific semantic categories of words.

When the Wedding March becomes sad: Semantic memory impairment for music in the semantic variant of primary progressive aphasia

ABSTRACTMusic can induce particular emotions and activate semantic knowledge. In the semantic variant of primary progressive aphasia (svPPA), semantic memory is impaired as a result of anterior temporal lobe (ATL) atrophy. Semantics is responsible for the encoding and retrieval of factual knowledge about music, including associative and emotional attributes. In the present study, we report the performance of two individuals with svPPA in three experiments. NG with bilateral ATL atrophy and ND with atrophy largely restricted to the left ATL. Experiment 1 assessed the recognition of musical excerpts and both patients were unimpaired. Experiment 2 studied the emotions conveyed by music and only NG showed impaired performance. Experiment 3 tested the association of semantic concepts to musical excerpts and both patients were impaired. These results suggest that the right ATL seems essential for the recognition of emotions conveyed by music and that the left ATL is involved in binding music to semantics. They are in line with the notion that the ATLs are devoted to the binding of different modality-specific properties and suggest that they are also differentially involved in the processing of factual and emotional knowledge associated with music.

Behavioural and neuroimaging changes after naming therapy for semantic variant primary progressive aphasia

The objectives of this study were to examine the effects of a successful naming intervention on naming performance and brain activity in individuals with the semantic variant of primary progressive aphasia (svPPA). Four participants with svPPA were scanned while performing phonologically- and semantically-based tasks before and after an intense, 20-h naming therapy that followed the principles of errorless learning whereby errors were eliminated from the learning process. Five healthy control participants were scanned at the outset of the study and did not receive treatment. The results showed that in svPPA participants, successful re-learning of forgotten vocabulary was accompanied by activation of a larger network in bilateral brain regions and that the level of activation in the left anterior lobe may be inversely correlated with severity of semantic impairment. Our findings have implications for treatment in svPPA patients and suggest that semantic cues can improve naming, in spite of significant semantic impairment. The results indicate that intensive language therapy can lead to behavioural gains and neuroplastic changes even in individuals with more advanced anterior temporal lobe atrophy.

Disorders of representation and control in semantic cognition: Effects of familiarity, typicality, and specificity

We present a case-series comparison of patients with cross-modal semantic impairments consequent on either (a) bilateral anterior temporal lobe atrophy in semantic dementia (SD) or (b) left-hemisphere fronto-parietal and/or posterior temporal stroke in semantic aphasia (SA). Both groups were assessed on a new test battery designed to measure how performance is influenced by concept familiarity, typicality and specificity. In line with previous findings, performance in SD was strongly modulated by all of these factors, with better performance for more familiar items (regardless of typicality), for more typical items (regardless of familiarity) and for tasks that did not require very specific classification, consistent with the gradual degradation of conceptual knowledge in SD. The SA group showed significant impairments on all tasks but their sensitivity to familiarity, typicality and specificity was more variable and governed by task-specific effects of these factors on controlled semantic processing. The results are discussed with reference to theories about the complementary roles of representation and manipulation of semantic knowledge.

Identification of environmental sounds and melodies in syndromes of anterior temporal lobe degeneration

Recognition of nonverbal sounds in semantic dementia and other syndromes of anterior temporal lobe degeneration may determine clinical symptoms and help to define phenotypic profiles. However, nonverbal auditory semantic function has not been widely studied in these syndromes. Here we investigated semantic processing in two key nonverbal auditory domains – environmental sounds and melodies – in patients with semantic dementia (SD group; n=9) and in patients with anterior temporal lobe atrophy presenting with behavioural decline (TL group; n=7, including four cases with MAPT mutations) in relation to healthy older controls (n=20). We assessed auditory semantic performance in each domain using novel, uniform within-modality neuropsychological procedures that determined sound identification based on semantic classification of sound pairs. Both the SD and TL groups showed comparable overall impairments of environmental sound and melody identification; individual patients generally showed superior identification of environmental sounds than melodies, however relative sparing of melody over environmental sound identification also occurred in both groups. Our findings suggest that nonverbal auditory semantic impairment is a common feature of neurodegenerative syndromes with anterior temporal lobe atrophy. However, the profile of auditory domain involvement varies substantially between individuals.

Semantic deficits in amyotrophic lateral sclerosis

Our objective was to investigate, and establish neuroanatomical correlates of, semantic deficits in amyotrophic lateral sclerosis (ALS) and amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD), compared to semantic dementia (SD) and controls. Semantic deficits were evaluated using a naming and semantic knowledge composite score, comprising verbal and non-verbal neuropsychological measures of single-word processing (confrontational naming, comprehension, and semantic association) from the Sydney Language Battery (SYDBAT) and Addenbrooke's Cognitive Examination – Revised (ACE-R). Voxel based morphometry (VBM) analysis was conducted using the region of interest approach. In total, 84 participants were recruited from a multidisciplinary research clinic in Sydney. Participants included 17 patients with ALS, 19 with ALS-FTD, 22 with SD and 26 age- and education-matched healthy controls. Significant semantic deficits were observed in ALS and ALS-FTD compared to controls. The severity of semantic deficits varied across the clinical phenotypes: ALS patients were less impaired than ALS-FTD patients, who in turn were not as impaired as SD patients. Anterior temporal lobe atrophy significantly correlated with semantic deficits. In conclusion, semantic impairment is a feature of ALS and ALS-FTD, and reflects the severity of temporal lobe pathology.

Preservation of lexical-semantic knowledge of adjectives in the semantic variant of primary progressive aphasia: Implications for theoretical models of semantic memory

Abstract Adjectives are lexical words used to modify nouns and refer to physical and concrete properties as well as abstract properties denoted by nouns. Although adjectives directly refer to semantic attributes, no study has explicitly examined the comprehension of adjectives in the semantic variant of primary progressive aphasia (svPPA). In this study, we explored the comprehension of adjectival meaning in four participants with svPPA using two experimental designs assessing the comprehension of adjectives per se and the comprehension of adjectives when associated with concrete nouns. We found evidence that participants: a) were unimpaired on tasks probing knowledge about adjectives referring to dimension and physical properties, to human propensity and value, and to color, but b) showed substantial difficulty when asked to associate the same adjectives with object nouns. These results raise important questions about the lexical-semantic representation of adjectives and, more generally, about the organization of words in the lexical-semantic system. The observed difficulties could be due to the impairment in binding different modality-specific properties and combining verbal conceptual knowledge, after anterior temporal lobe atrophy.

IDENTIFICATION OF ENVIRONMENTAL SOUNDS AND MELODIES IN SYNDROMES OF ANTERIOR TEMPORAL LOBE DEGENERATION

article i nfo Recognition of nonverbal sounds in semantic dementia and other syndromes of anterior temporal lobe degener- ation may determine clinical symptoms and help to define phenotypic profiles. However, nonverbal auditory semantic function has not been widely studied in these syndromes. Here we investigated semantic processing in two key nonverbal auditory domains - environmental sounds and melodies - in patients with semantic dementia (SD group; n = 9) and in patients with anterior temporal lobe atrophy presenting with behavioural decline (TL group; n = 7, including four cases with MAPT mutations) in relation to healthy older controls (n = 20). We assessed auditory semantic performance in each domain using novel, uniform within-modality neuropsychological procedures that determined sound identification based on semantic classification of sound pairs. Both the SD and TL groups showed comparable overall impairments of environmental sound and melody identification; individual patients generally showed superior identification of environmental sounds than melodies, however relative sparing of melody over environmental sound identification also occurred in both groups. Our findings suggest that nonverbal auditory semantic impairment is a common feature of neurodegen- erative syndromes with anterior temporal lobe atrophy. However, the profile of auditory domain involvement varies substantially between individuals. © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license

‘THE MIND IS ITS OWN PLACE’: AMELIORATION OF CLAUSTROPHOBIA IN A PATIENT WITH SEMANTIC DEMENTIA

Specific phobia is defined as marked, persistent and excessive or unreasonable fear when in the presence of, or when anticipating an encounter with, a specific object or situation.1 Here we...

Corticospinal tract degeneration associated with TDP-43 type C pathology and semantic dementia

Four subtypes of frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions have been described (types A-D). Of these four subtypes, motor neuron disease is more commonly associated with type B pathology, but has also been reported with type A pathology. We have noted, however, the unusual occurrence of cases of type C pathology having corticospinal tract degeneration. We aimed to assess the severity of corticospinal tract degeneration in a large cohort of cases with type C (n = 31). Pathological analysis included semi-quantitation of myelin loss of fibres of the corticospinal tract and associated macrophage burden, as well as axonal loss, at the level of the medullary pyramids. We also assessed for motor cortex degeneration and fibre loss of the medial lemniscus/olivocerebellar tract. All cases were subdivided into three groups based on the degree of corticospinal tract degeneration: (i) no corticospinal tract degeneration; (ii) equivocal corticospinal tract degeneration; and (iii) moderate to very severe corticospinal tract degeneration. Clinical, genetic, pathological and imaging comparisons were performed across groups. Eight cases had no corticospinal tract degeneration, and 14 cases had equivocal to mild corticospinal tract degeneration. Nine cases, however, had moderate to very severe corticospinal tract degeneration with myelin and axonal loss. In these nine cases, there was degeneration of the motor cortex without lower motor neuron degeneration or involvement of other brainstem tracts. These cases most commonly presented as semantic dementia, and they had longer disease duration (mean: 15.3 years) compared with the other two groups (10.8 and 9.9 years; P = 0.03). After adjusting for disease duration, severity of corticospinal tract degeneration remained significantly different across groups. Only one case, without corticospinal tract degeneration, was found to have a hexanucleotide repeat expansion in the C9ORF72 gene. All three groups were associated with anterior temporal lobe atrophy on MRI; however, the cases with moderate to severe corticospinal tract degeneration showed right-sided temporal lobe asymmetry and greater involvement of the right temporal lobe and superior motor cortices than the other groups. In contrast, the cases with no or equivocal corticospinal tract degeneration were more likely to show left-sided temporal lobe asymmetry. For comparison, the corticospinal tract was assessed in 86 type A and B cases, and only two cases showed evidence of corticospinal tract degeneration without lower motor neuron degeneration. These findings confirm that there exists a unique association between frontotemporal lobar degeneration with type C pathology and corticospinal tract degeneration, with this entity showing a predilection to involve the right temporal lobe.

Naming impairment in Alzheimer's disease is associated with left anterior temporal lobe atrophy

There is considerable debate about the neuroanatomic localization of semantic memory, the knowledge of culturally shared elements such as objects, concepts, and people. Two recent meta-analyses of functional imaging studies (fMRI and PET) sought to identify cortical regions involved in semantic processing. Binder and colleagues (Binder et al., 2009) identified several regions of interest, widely distributed throughout the frontal, parietal, and temporal cortices. In contrast, Lambon Ralph and colleagues (2010) focused on the anterior temporal lobe, and found that when the potential for signal loss is accounted for (due, for example, to distortion artifact or field of view restriction), significant regional activation is detected. We set out to determine whether the anterior temporal lobe plays a significant role in picture naming, a task which relies on semantic memory. We examined a relatively large sample of patients with early Alzheimer's disease (N=145), a multifocal disease process typically characterized in the early stages by problems with episodic memory and executive function. Hypothesis-driven analyses based on regions of interest derived from the meta-analyses as well as exploratory analyses across the entire cerebral cortex demonstrated a highly specific correlation between cortical thinning of the left anterior temporal lobe and impaired naming performance. These findings lend further support to theories that include a prominent role for the anterior temporal lobe in tasks that rely on semantic memory.

Asymmetric cortical surface area and morphology changes in mesial temporal lobe epilepsy with hippocampal sclerosis

To date, magnetic resonance imaging (MRI)-based studies of the cerebral cortex in mesial temporal lobe epilepsy (MTLE) have focused primarily on investigating cortical volume and thickness. However, volume is a composite of surface area and thickness, each reflecting distinct neurobiologic and genetic processes. The goal of this study was to investigate cerebral cortex (1) surface area, (2) surface geometric distortion, and (3) thickness in MTLE with hippocampal sclerosis (HS). Seventy patients with "sporadic" unilateral MTLE + HS and 40 healthy controls underwent T(1) -weighted MRI. Processing MR images using an automated cortical surface reconstruction method (FreeSurfer), we quantified cortical surface area, surface geometric distortion (metric distortion), and thickness at each vertex across the entire cortex. Differences between patients and controls were determined using generalized linear models. Separate linear regression models were employed to assess the relationship between cortical surface area and hippocampal volume as well as a series of important clinical features of the condition. We detected an asymmetric reduction in cortical surface area, predominantly in ipsilateral mesial and anterior temporal lobe subregions, of patients with MTLE + HS. Changes in surface geometric features were also evident and closely mirrored surface area patterns. In contrast, cortical thinning appeared dispersed across the cortex bilaterally. The regression models revealed that ipsilateral hippocampal volume was a significant predictor of temporal lobe surface area changes. Our findings indicate that contraction in surface area, rather than cortical thinning, explains ipsilateral mesial and anterior temporal lobe atrophy in patients with MTLE with HS. Furthermore, the alterations in surface geometry indicate folding abnormality involving the same regions. Cortical surface changes may represent sequelae of the disease or deviant cortical development.