Posterior Temporal Cortex Research Articles

The Effect of ECT On Brain Grey Matter, Insights From Longitudinal MRI

Despite the highly beneficial effects of ECT in the elderly, the close relationship between brain structure and LLD and the possible predictive value of structural changes on ECT response in LLD, no study has addressed the effects of ECT on gray matter volume (GMV) in the elderly so far. In this presentation we review recent studies elucidating neural effects of ECT in non-elderly cohorts and present a longitudinal structural neuroimaging study in a cohort of 28 elderly subjects to compare GMV before and after ECT. Given the different cortical and subcortical areas implicated in LLD and the absence of previous studies revealing specific regions of interest, we applied a whole brain approach (voxel-based morphometry (VMB)) to explore structural changes. We also investigated the correlation between structural changes and changes in mood, cognition and psychomotor function (given their clinical relevance in LLD). We observed significant right-hemispheric GMV increase in the caudate nucleus, medial temporal lobe (including hippocampus and amygdala), insula and posterior superior temporal cortex. Furthermore, a correlation was found between the increase of GMV in the caudate nucleus region and the change in psychomotor function scores indicating interesting and potentially specific clinical associations. Potential neurobiological mechanisms underlying these GMV increases will be discussed.

Functional MRI of music emotion processing in frontotemporal dementia.

Frontotemporal dementia is an important neurodegenerative disorder of younger life led by profound emotional and social dysfunction. Here we used fMRI to assess brain mechanisms of music emotion processing in a cohort of patients with frontotemporal dementia (n = 15) in relation to healthy age-matched individuals (n = 11). In a passive-listening paradigm, we manipulated levels of emotion processing in simple arpeggio chords (mode versus dissonance) and emotion modality (music versus human emotional vocalizations). A complex profile of disease-associated functional alterations was identified with separable signatures of musical mode, emotion level, and emotion modality within a common, distributed brain network, including posterior and anterior superior temporal and inferior frontal cortices and dorsal brainstem effector nuclei. Separable functional signatures were identified post-hoc in patients with and without abnormal craving for music (musicophilia): a model for specific abnormal emotional behaviors in frontotemporal dementia. Our findings indicate the potential of music to delineate neural mechanisms of altered emotion processing in dementias, with implications for future disease tracking and therapeutic strategies.

Conceptual control across modalities: graded specialisation for pictures and words in inferior frontal and posterior temporal cortex

Controlled semantic retrieval to words elicits co-activation of inferior frontal (IFG) and left posterior temporal cortex (pMTG), but research has not yet established (i) the distinct contributions of these regions or (ii) whether the same processes are recruited for non-verbal stimuli. Words have relatively flexible meanings – as a consequence, identifying the context that links two specific words is relatively demanding. In contrast, pictures are richer stimuli and their precise meaning is better specified by their visible features – however, not all of these features will be relevant to uncovering a given association, tapping selection/inhibition processes. To explore potential differences across modalities, we took a commonly-used manipulation of controlled retrieval demands, namely the identification of weak vs. strong associations, and compared word and picture versions. There were 4 key findings: (1) Regions of interest (ROIs) in posterior IFG (BA44) showed graded effects of modality (e.g., words>pictures in left BA44; pictures>words in right BA44). (2) An equivalent response was observed in left mid-IFG (BA45) across modalities, consistent with the multimodal semantic control deficits that typically follow LIFG lesions. (3) The anterior IFG (BA47) ROI showed a stronger response to verbal than pictorial associations, potentially reflecting a role for this region in establishing a meaningful context that can be used to direct semantic retrieval. (4) The left pMTG ROI also responded to difficulty across modalities yet showed a stronger response overall to verbal stimuli, helping to reconcile two distinct literatures that have implicated this site in semantic control and lexical-semantic access respectively. We propose that left anterior IFG and pMTG work together to maintain a meaningful context that shapes ongoing semantic processing, and that this process is more strongly taxed by word than picture associations.

New insights into the neural network mediating reading processes provided by cortico-subcortical electrical mapping.

To ascertain the neural network mediating reading using intraoperative electrostimulation. A cortical and axonal intraoperative electrical mapping of reading processes was achieved in seven patients who underwent awake surgery for a left occipitotemporal glioma. We performed resection cavity overlapping and superimposition with a diffusion tensor imaging-based white matter atlas. We assessed the relationship between the location of resection cavities and the occurrence of reading impairments of regular, irregular, and pseudowords. Intraoperative stimulation of the left posterior inferior temporal cortex (ITCp) elicited reading disturbances. Subcortical stimulation at the anterior portion of the visual word form area (VWFA) induced addressed phonology (irregular words reading) disturbances. Subcortical stimulation of the connection between VWFA and the posterior segment of the arcuate fascicle (AFp) induced both addressed and assembled phonology (irregular and pseudowords reading) disturbances. Postoperative assessment showed that resection of the posterior portion of the inferior longitudinal fascicle (ILFp), connecting the visual cortex to VWFA, induced long-term and global reading impairment. Resection of the terminations of left AFp in the ITCp-induced irregular and pseudowords reading disturbances with no impairment of regular words reading. Resection of the anterior portion of ILF did not induce reading impairment. Our data support an inner posterior-to-anterior hierarchical coding of letter strings in the VWFA and a crucial role of the left ILFp to provide visual inputs to the VWFA. Furthermore, we suggest that the AFp is involved in an interactive feedback system between visual and nonvisual information, recruited when reading irregular and pseudowords.

34. Structural connectivity of eloquent speech areas defined by direct cortical stimulation mapping

Background and aims The anatomical borders of eloquent speech areas, e.g. Broca's area, have been vaguely defined and exhibit high inter-subject variability (Amunts and Zilles, 2012), mainly due to inconsistent morphology of the inferior frontal gyrus (IFG) (Ebeling et al., 1989) and small-scale incongruity of functional segregation with respect to anatomical landmarks (Garrett et al., 2012; Quinones-Hinojosa et al., 2003). However, knowing the exact boundaries of the eloquent cortex became clinically important in preventing postoperative deficits after brain surgery (Garrett et al., 2012; Hollon et al., 2015). The awake electrical stimulation mapping (ESM) has become the preferred method to delineate the speech cortex, as the current non-invasive alternatives lack specificity and spatial resolution (Garrett et al., 2012; Hollon et al., 2015). Since the structural connectivity-based parcellation using diffusion tensor imaging (DTI) has been shown to closely relate to the cytoarchitectonics in the IFG (Klein et al., 2007), we tested whether the location of eloquent cortex could be better predicted by preoperative DTI rather than by its relation to gyrification. Methods Seventeen patients (8 males, median age 33, range 18–63) suffering from primary brain tumor underwent pre-operative 3T MRI scanning using a high resolution T1 MPRAGE and a single shell diffusion weighted imaging (DWI) sequence (60 directions, b =1000 s/mm 2 , resolution 2×2×2mm), and intraoperative direct cortical electrical stimulation with a bipolar Ojemann electrode during awake language mapping. After standard preprocessing, probabilistic fiber tracking (PROBTRACKX in FSL (Behrens et al., 2007)) was carried out using 5mm spheres as cortico-subcortical seeds placed at the intraoperatively defined positive stimulation sites. The resulting cortical projections were then overlaid onto the individual cortex surface (Freesurfer) and compared visually and using binary logical operations. Results A variety of stimulation-positive functional sites was detected, producing anomia, counting, speech and motor arrest. Anomia sites were found both in the pars triangularis and pars opercularis of the inferior frontal gyrus (also in individual patients). Even opercular anomia sites followed the connectivity pattern of triangular anomia sites and had stronger connections to the rostral parts of the mesial prefrontal cortex and pre-supplementary motor area (pre-SMA) than to the precentral gyrus and SMA proper, as opposed to opercular speech or counting arrest sites which also connected more strongly to more posterior parts of the brain, mostly posterior temporal cortex. Thus, even adjacent sites on the same gyrus that differed in function showed dissociable structural connectivity. Conclusions Our results suggest that structure–function relationships are more evident between function and structural connectivity than between function and gyrification. Acknowledgement This study was supported by the German Research Foundation, the European Union, and the German Academic Exchange Service (DAAD).

Shared neural processes support semantic control and action understanding

Executive–semantic control and action understanding appear to recruit overlapping brain regions but existing evidence from neuroimaging meta-analyses and neuropsychology lacks spatial precision; we therefore manipulated difficulty and feature type (visual vs. action) in a single fMRI study. Harder judgements recruited an executive–semantic network encompassing medial and inferior frontal regions (including LIFG) and posterior temporal cortex (including pMTG). These regions partially overlapped with brain areas involved in action but not visual judgements. In LIFG, the peak responses to action and difficulty were spatially identical across participants, while these responses were overlapping yet spatially distinct in posterior temporal cortex. We propose that the co-activation of LIFG and pMTG allows the flexible retrieval of semantic information, appropriate to the current context; this might be necessary both for semantic control and understanding actions. Feature selection in difficult trials also recruited ventral occipital–temporal areas, not implicated in action understanding.

Classifying adolescent attention-deficit/hyperactivity disorder (ADHD) based on functional and structural imaging

Attention-deficit/hyperactivity disorder (ADHD) is a common disabling psychiatric disorder associated with consistent deficits in error processing, inhibition and regionally decreased grey matter volumes. The diagnosis is based on clinical presentation, interviews and questionnaires, which are to some degree subjective and would benefit from verification through biomarkers. Here, pattern recognition of multiple discriminative functional and structural brain patterns was applied to classify adolescents with ADHD and controls. Functional activation features in a Flanker/NoGo task probing error processing and inhibition along with structural magnetic resonance imaging data served to predict group membership using support vector machines (SVMs). The SVM pattern recognition algorithm correctly classified 77.78% of the subjects with a sensitivity and specificity of 77.78% based on error processing. Predictive regions for controls were mainly detected in core areas for error processing and attention such as the medial and dorsolateral frontal areas reflecting deficient processing in ADHD (Hart et al., in Hum Brain Mapp 35:3083-3094, 2014), and overlapped with decreased activations in patients in conventional group comparisons. Regions more predictive for ADHD patients were identified in the posterior cingulate, temporal and occipital cortex. Interestingly despite pronounced univariate group differences in inhibition-related activation and grey matter volumes the corresponding classifiers failed or only yielded a poor discrimination. The present study corroborates the potential of task-related brain activation for classification shown in previous studies. It remains to be clarified whether error processing, which performed best here, also contributes to the discrimination of useful dimensions and subtypes, different psychiatric disorders, and prediction of treatment success across studies and sites.

The influence of handedness on hemispheric representation of tools: A survey

An important debate exists in contemporary cognitive neuroscience about the innate or experience-dependent origin of the brain representation of conceptual categories. The ‘domains of knowledge’ hypothesis maintains that innate factors subsume the categorical organization at the brain level of animals, plant life and artefacts. On the other hand, the ‘sensory-motor model of conceptual knowledge’ and the embodied cognition theory attribute this categorical organization to experience-dependent factors. I tried to clarify this issue by surveying the influence that handedness could have on the lateralization of tools representation in the inferior fronto-parietal and posterior middle temporal cortices of the left hemisphere. The underlying assumption was that, if this lateralization results from innate mechanisms, then handedness should not influence this hemispheric asymmetry. If, on the other hand, this lateralization is due to the motor and somatosensory experiences made with the right dominant hand during the manipulation of tools and other artefacts, then this asymmetry should be inverted or strongly attenuated in left-handers. Results of the review strongly suggest that manual experience acquired during tool manipulation can influence the hemispheric representation of tools and other artefacts. They also suggest, however, that handedness-related embodiment is not fixed, but influenced by personal motor experiences (such as those made by left-handers who have been forced to use their right hand) and by social visual experiences (such as the fact that, living in a right-handed world, left-handers see more people in their environment who use the right rather than the left hand) during tool manipulation.

Cortical structural abnormalities in very preterm children at 7 years of age

We analyzed long-lasting alterations in brain morphometry associated with preterm birth using volumetric and surface-based analyses applied to children at age 7years. Comparison of 24 children born very preterm (VPT) to 24 healthy term-born children revealed reductions in total cortical gray matter volume, white matter volume, cortical surface area and gyrification index. Regional cortical shape abnormalities in VPT children included the following: shallower anterior superior temporal sulci, smaller relative surface area in the inferior sensori-motor cortex and posterior superior temporal cortex, larger relative surface area and a cingulate sulcus that was shorter or more interrupted in medial frontoparietal cortex. These findings indicate a complex pattern of regional vulnerabilities in brain development that may contribute to the diverse and long-lasting neurobehavioral consequences that can occur after very premature birth.

Functional neuroanatomy of auditory scene analysis in Alzheimer's disease.

Auditory scene analysis is a demanding computational process that is performed automatically and efficiently by the healthy brain but vulnerable to the neurodegenerative pathology of Alzheimer's disease. Here we assessed the functional neuroanatomy of auditory scene analysis in Alzheimer's disease using the well-known ‘cocktail party effect’ as a model paradigm whereby stored templates for auditory objects (e.g., hearing one's spoken name) are used to segregate auditory ‘foreground’ and ‘background’. Patients with typical amnestic Alzheimer's disease (n = 13) and age-matched healthy individuals (n = 17) underwent functional 3T-MRI using a sparse acquisition protocol with passive listening to auditory stimulus conditions comprising the participant's own name interleaved with or superimposed on multi-talker babble, and spectrally rotated (unrecognisable) analogues of these conditions. Name identification (conditions containing the participant's own name contrasted with spectrally rotated analogues) produced extensive bilateral activation involving superior temporal cortex in both the AD and healthy control groups, with no significant differences between groups. Auditory object segregation (conditions with interleaved name sounds contrasted with superimposed name sounds) produced activation of right posterior superior temporal cortex in both groups, again with no differences between groups. However, the cocktail party effect (interaction of own name identification with auditory object segregation processing) produced activation of right supramarginal gyrus in the AD group that was significantly enhanced compared with the healthy control group. The findings delineate an altered functional neuroanatomical profile of auditory scene analysis in Alzheimer's disease that may constitute a novel computational signature of this neurodegenerative pathology.

Chapter 10 - White-matter pathways for speech and language processing

The language-relevant brain regions, Brodmann's area in the inferior frontal cortex and Wernicke's area in the superior temporal cortex, are connected via long-range fiber bundles, which are located dorsally and ventrally to the sylvian fissure. These dorsal and ventral pathways consist of a number of partly parallel-running fiber tracts, which can be differentiated by their termination regions and by the particular language functions of these termination regions. Dorsally, there are two major fiber tracts connecting the posterior temporal cortex with the frontal cortex: one terminating in the premotor cortex that subserves sensory-to-motor mapping and one terminating in posterior Broca's area, the pars opercularis, that supports the processing of complex syntactic structures. Ventrally, two language-related fiber tracts are discussed: one connects the inferior frontal cortex, i.e., the pars triangularis and orbitalis, with Wernicke's area and supports semantic processes and another one connects the most ventral portions of the inferior frontal cortex, including the frontal operculum, with the anterior temporal cortex. This latter ventral tract is suggested to subserve elementary combinatorial processes in language. Together these fiber tracts guarantee the transmission of information between different brain regions within the neural language network.

Visuospatial complexity modulates reading in the brain

Neurocognitive processing of orthographic visuospatial complexity was examined through fMRI-based overt naming (n=16) of phonologically transparent, high and low frequency Hindi/Devanagari words that were visually simple (पालक, चातक) or complex (▪, चकली). Participants’ overt behavior was modestly influenced by visuospatial complexity (accuracy: main effect p=.01, complexity×frequency interaction p<.07), while neuroimaging data revealed a robust effect of complexity (main effect FWE p<10−4, complexity×frequency interaction FWE p<7×10−8). Interaction-based RoIs showed higher BOLD response in the VWFA to complex and left posterior temporal cortex to simple words, with greater right lingual de-activation to complex than simple words. Subtractions confirmed additional recruitment of VWFA, right frontal, inferior orbitofrontal, mid-temporal pole and left cerebellum by visuospatially complex over simple words. Finally, low frequency words activated bilateral occipital and putamen areas, left IPL, SPL, IFG and VWFA, suggesting that effortful phonological processing in alphasyllabic Hindi/Devanagari requires neural resources specialized for both visuospatially simple and complex orthographies.

Increased Visual Stimulation Systematically Decreases Activity in Lateral Intermediate Cortex.

Previous studies have attributed multiple diverse roles to the posterior superior temporal cortex (STC), both visually driven and cognitive, including part of the default mode network (DMN). Here, we demonstrate a unifying property across this multimodal region. Specifically, the lateral intermediate (LIM) portion of STC showed an unexpected feature: a progressively decreasing fMRI response to increases in visual stimulus size (or number). Such responses are reversed in sign, relative to well-known responses in classic occipital temporal visual cortex. In LIM, this “reversed” size function was present across multiple object categories and retinotopic eccentricities. Moreover, we found a significant interaction between the LIM size function and the distribution of subjects' attention. These findings suggest that LIM serves as a part of the DMN. Further analysis of functional connectivity, plus a meta-analysis of previous fMRI results, suggests that LIM is a heterogeneous area including different subdivisions. Surprisingly, analogous fMRI tests in macaque monkeys did not reveal a clear homolog of LIM. This interspecies discrepancy supports the idea that self-referential thinking and theory of mind are more prominent in humans, compared with monkeys.

Acoustic cue selection and discrimination under degradation: Differential contributions of the inferior parietal and posterior temporal cortices

Auditory categorization is a vital skill for perceiving the acoustic environment. Categorization depends on the discriminability of the sensory input as well as on the ability of the listener to adaptively make use of the relevant features of the sound. Previous studies on categorization have focused either on speech sounds when studying discriminability or on visual stimuli when assessing optimal cue utilization. Here, by contrast, we examined neural sensitivity to stimulus discriminability and optimal cue utilization when categorizing novel, non-speech auditory stimuli not affected by long-term familiarity. In a functional magnetic resonance imaging (fMRI) experiment, listeners categorized sounds from two category distributions, differing along two acoustic dimensions: spectral shape and duration. By introducing spectral degradation after the first half of the experiment, we manipulated both stimulus discriminability and the relative informativeness of acoustic cues. Degradation caused an overall decrease in discriminability based on spectral shape, and therefore enhanced the informativeness of duration. A relative increase in duration-cue utilization was accompanied by increased activity in left parietal cortex. Further, discriminability modulated right planum temporale activity to a higher degree when stimuli were spectrally degraded than when they were not. These findings provide support for separable contributions of parietal and posterior temporal areas to perceptual categorization. The parietal cortex seems to support the selective utilization of informative stimulus cues, while the posterior superior temporal cortex as a primarily auditory brain area supports discriminability particularly under acoustic degradation.

Neural pathways for visual speech perception.

This paper examines the questions, what levels of speech can be perceived visually, and how is visual speech represented by the brain? Review of the literature leads to the conclusions that every level of psycholinguistic speech structure (i.e., phonetic features, phonemes, syllables, words, and prosody) can be perceived visually, although individuals differ in their abilities to do so; and that there are visual modality-specific representations of speech qua speech in higher-level vision brain areas. That is, the visual system represents the modal patterns of visual speech. The suggestion that the auditory speech pathway receives and represents visual speech is examined in light of neuroimaging evidence on the auditory speech pathways. We outline the generally agreed-upon organization of the visual ventral and dorsal pathways and examine several types of visual processing that might be related to speech through those pathways, specifically, face and body, orthography, and sign language processing. In this context, we examine the visual speech processing literature, which reveals widespread diverse patterns of activity in posterior temporal cortices in response to visual speech stimuli. We outline a model of the visual and auditory speech pathways and make several suggestions: (1) The visual perception of speech relies on visual pathway representations of speech qua speech. (2) A proposed site of these representations, the temporal visual speech area (TVSA) has been demonstrated in posterior temporal cortex, ventral and posterior to multisensory posterior superior temporal sulcus (pSTS). (3) Given that visual speech has dynamic and configural features, its representations in feedforward visual pathways are expected to integrate these features, possibly in TVSA.

Functional Changes in the Language Network in Response to Increased Amyloid β Deposition in Cognitively Intact Older Adults.

Word finding symptoms are frequent early in the course of Alzheimer's disease and relate principally to functional changes in left posterior temporal cortex. In cognitively intact older adults, we examined whether amyloid load affects the network for language and associative-semantic processing. Fifty-six community-recruited subjects (52-74 years), stratified for apolipoprotein E and brain-derived neurotrophic factor genotype, received a neurolinguistic assessment, (18)F-flutemetamol positron emission tomography, and a functional MRI of the associative-semantic system. The primary measure of amyloid load was the cerebral-to-cerebellar gray matter standardized uptake value ratio in a composite cortical volume of interest (SUVR(comp)). The primary outcome analysis consisted of a whole-brain voxelwise linear regression between SUVR(comp) and fMRI response during associative-semantic versus visuoperceptual processing. Higher activity in one region, the posterior left middle temporal gyrus, correlated positively with increased amyloid load. The correlation remained significant when only the word conditions were contrasted but not for pictures. According to a stepwise linear regression analysis, offline naming reaction times correlated positively with SUVR(comp). A binary classification into amyloid-positive and amyloid-negative cases confirmed our findings. The left posterior temporal activity increase may reflect higher demands for semantic control in the presence of a higher amyloid burden.

Uncovering the spatio-temporal dynamics of value-based decision-making in the human brain: a combined fMRI-EEG study.

While there is a growing body of functional magnetic resonance imaging (fMRI) evidence implicating a corpus of brain regions in value-based decision-making in humans, the limited temporal resolution of fMRI cannot address the relative temporal precedence of different brain regions in decision-making. To address this question, we adopted a computational model-based approach to electroencephalography (EEG) data acquired during a simple binary choice task. fMRI data were also acquired from the same participants for source localization. Post-decision value signals emerged 200 ms post-stimulus in a predominantly posterior source in the vicinity of the intraparietal sulcus and posterior temporal lobe cortex, alongside a weaker anterior locus. The signal then shifted to a predominantly anterior locus 850 ms following the trial onset, localized to the ventromedial prefrontal cortex and lateral prefrontal cortex. Comparison signals between unchosen and chosen options emerged late in the trial at 1050 ms in dorsomedial prefrontal cortex, suggesting that such comparison signals may not be directly associated with the decision itself but rather may play a role in post-decision action selection. Taken together, these results provide us new insights into the temporal dynamics of decision-making in the brain, suggesting that for a simple binary choice task, decisions may be encoded predominantly in posterior areas such as intraparietal sulcus, before shifting anteriorly.

Preserved mid-fusiform activation for visual words in a patient with a visual word recognition impairment

Previous functional imaging studies have highlighted the role of left ventral temporal cortex in processing written word forms. We explored activation and anatomical connectivity of this region in HE, a professional writer with alexia as a result of stroke affecting primarily white matter in the left inferior temporal lobe. We used a one-back visual recognition task and functional Magnetic Resonance Imaging to elicit automatic activation to various orthographic and non-orthographic stimuli. Surprisingly, HE showed cortical activation in the left mid-fusiform area during the presentation of words and word-like stimuli, suggesting that this region׳s role in processing visual words is intact despite his severely impaired reading. Diffusion Tensor Imaging data further suggest that HE shows an anatomical disconnection between the ventral temporal cortex and posterior middle temporal cortex. Together, these findings suggest that activation of word-specific regions of mid-fusiform gyrus is not sufficient to yield the conscious experience of reading in the absence of activity in downstream regions of the classical reading network.

When "ultrarapid" word-related motor activity is not faster than "early".

When "ultrarapid" word-related motor activity is not faster than "early".

Abnormal development of sensory-motor, visual temporal and parahippocampal cortex in children with learning disabilities and borderline intellectual functioning.

Borderline intellectual functioning (BIF) is a condition characterized by an intelligence quotient (IQ) between 70 and 85. BIF children present with cognitive, motor, social, and adaptive limitations that result in learning disabilities and are more likely to develop psychiatric disorders later in life. The aim of this study was to investigate brain morphometry and its relation to IQ level in BIF children. Thirteen children with BIF and 14 age- and sex-matched typically developing (TD) children were enrolled. All children underwent a full IQ assessment (WISC-III scale) and a magnetic resonance (MR) examination including conventional sequences to assess brain structural abnormalities and high resolution 3D images for voxel-based morphometry analysis. To investigate to what extent the group influenced gray matter (GM) volumes, both univariate and multivariate generalized linear model analysis of variance were used, and the varimax factor analysis was used to explore variable correlations and clusters among subjects. Results showed that BIF children, compared to controls have increased regional GM volume in bilateral sensorimotor and right posterior temporal cortices and decreased GM volume in the right parahippocampal gyrus. GM volumes were highly correlated with IQ indices. The present work is a case study of a group of BIF children showing that BIF is associated with abnormal cortical development in brain areas that have a pivotal role in motor, learning, and behavioral processes. Our findings, although allowing for little generalization to the general population, contribute to the very limited knowledge in this field. Future longitudinal MR studies will be useful in verifying whether cortical features can be modified over time even in association with rehabilitative intervention.