Author name cluster

Julius Fridriksson

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21 papers

1 author row

YNIMG Journal 2026 Journal Article

Regional brain atrophy mediates age effects on words recognition in noise in adults

Samin Ashjaei
Julius Fridriksson
Leonardo Bonilha
Roger Newman-Norlund
Sigfus Kristinsson
Jean Neils-Strunjas
Sarah Newman-Norlund
Ida Rangus

Aging in adults is associated with a decline in speech-in-noise (SiN) recognition, yet the neural mechanisms driving this decline remain insufficiently characterized. Most neural evidence on age-related SiN performance has relied on correlational approaches that describe how SiN ability is related to age, but it is not yet clear how changes in specific brain structures mediate this relationship. Moreover, it remains unclear how such mediation manifests when hearing sensitivity is clinically normal. The present study applied a brain-wide, region-level mediation framework to identify the neural pathways through which regional brain atrophy mediates age effects on SiN performance. We studied data from 208 adults (aged 20-80 years; M = 49.5, SD = 19.6) who participated in the Aging Brain Cohort (ABC) Study at the University of South Carolina. Participants completed pure-tone audiometry (PTA) test, the Words-in-Noise (WIN) test, and underwent high-resolution structural MRI. Regional gray- and white-matter volumes were derived using the Johns Hopkins University atlas, and mediation was assessed using the graphical Brain Association Tool (gBAT) to systematically examine how reduced brain volume mediates age-WIN recognition link. A secondary analysis examined mediation effects in a subgroup of 150 participants with clinically normal hearing sensitivity. Behavioral results showed that each additional decade of life was associated with approximately 1.3 dB SNR increase in WIN thresholds. Whole-brain mediation analyses showed that age-related atrophy in regions supporting selective attention, error monitoring, working memory, motor control, and multimodal cue integration mediated age-associated declines in SiN recognition. These neural mediation effects persisted, though with reduced magnitude, in the subgroup with clinically normal hearing sensitivity. The results identify brain structural mechanisms underlying SiN difficulties and emphasize that age-related changes in brain structure impair SiN performance even when audibility remains intact.

YNICL Journal 2025 Journal Article

Hypoperfusion regions linked to National Institutes of Health Stroke Scale scores in acute stroke

Hana Kim
Alex Teghipco
Chris Rorden
Julius Fridriksson
Mathew Chaves
Argye E. Hillis

BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) is widely used to assess stroke severity. While prior studies have identified subcortical regions where infarcts correlate with NIHSS scores, stroke symptoms can also arise from hypoperfusion, not just infarcts. Understanding the potential for neurological recovery post-reperfusion is essential for guiding treatment decisions. The goal of this study was to identify brain regions where hypoperfusion correlates with NIHSS scores, using computed tomography perfusion (CTP) scans in cases of acute ischemic stroke. METHODS: In this prospective observational study, we analyzed CTP scans and NIHSS scores from 89 patients in the acute phase. We employed a unique support vector regression approach to overcome limitations of traditional mass univariate analyses. Additionally, we used stability selection to identify the most consistent features across subsets, reducing overfitting and ensuring robust predictive models. We verified the consistency of results through nested cross-validation. RESULTS: Both cortical and subcortical areas, including white matter tracts, showed associations with NIHSS scores. These regions aligned with functions such as language, spatial attention, sensory, and motor skills, all assessed by the NIHSS. CONCLUSIONS: Our findings reveal that hypoperfusion in specific brain regions, including previously underreported cortical areas, contributes to NIHSS scores in acute stroke. Moreover, this study introduces a novel brain mapping approach using CTP imaging and stability selection, offering a more comprehensive view of acute stroke impairments and the potential for recovery before structural reorganization occurs.

YNICL Journal 2025 Journal Article

Mapping the path to degeneration: How lesion location predicts post-stroke cerebellar atrophy

Makayla Gibson
Roger Newman-Norlund
Janina Wilmskoetter
Sigfus Kristinsson
Leonardo Bonilha
Julius Fridriksson
Chris Rorden

INTRODUCTION: Stroke can lead to neurological changes beyond the initial lesion site, including post-stroke crossed-cerebellar degeneration. While traditional methods typically rely on total lesion volume to assess remote effects, the spatial distribution of lesions may more accurately predict cerebellar atrophy and associated functional deficits. This study investigated whether anatomically specific cortical lesions contribute to cerebellar gray matter volume loss, expanding on the hypothesis that cerebellar atrophy may reflect more than global brain injury severity, and instead result from targeted disruption of cortico-cerebellar pathways. METHODS: Data from 142 chronic left hemisphere stroke participants (57 females, 85 males; M = 61 years) were analyzed using voxel-based lesion-symptom mapping (VLSM) and region of interest (ROI) analyses. High-resolution structural MRI scans were processed to quantify cerebellar gray matter volume (GMV) across 28 spatially distinct regions, with lesions manually delineated and mapped. RESULTS: Significant associations were found between lesion load in specific white matter tracts and cerebellar GMV atrophy. Lesions in the posterior limb of the internal capsule, retrolenticular part of the internal capsule, fornix/stria terminalis and superior corona radiata were strongly linked to GMV reductions in right cerebellar lobules and vermis. Notably, cortical lesions primarily impacted the right cerebellar regions, supporting the concept of post-stroke crossed cerebellar diaschisis. In a complementary analysis, voxel-based lesion-symptom mapping using Apraxia of Speech (AOS) severity scores revealed overlapping lesion predictors with those driving cerebellar degeneration, particularly within the superior corona radiata and retrolenticular part of the internal capsule. This overlap suggests that damage to these tracts may contribute jointly to speech-motor impairment and remote cerebellar atrophy. CONCLUSION: The spatial distribution of cortical lesions, rather than total lesion volume, plays a crucial role in predicting cerebellar degeneration. These findings suggest the importance of considering lesion location in stroke rehabilitation, and provide further insights into the functional connections between the cerebrum and cerebellum.

YNIMG Journal 2025 Journal Article

White matter integrity of hearing and cognitive impairments in healthy aging

Samaneh Nemati
Meisam Arjmandi
Jean Neils-Strunjas
Roger D. Newman-Norlund
Sarah E. Newman-Norlund
Laura Droege
Leonardo Bonilha
Julius Fridriksson

Age-Related Hearing Loss (ARHL), or presbycusis, affects two-thirds of U.S. adults over 70 and is linked to cognitive decline and an increased risk of dementia. This study examines associations between white matter integrity and hearing and cognitive function in healthy aging using diffusion tensor imaging (DTI). We recruited 126 participants (92 female) aged 20-79 years (Mean=51.34,SD=20.54) from the Aging Brain Cohort Study at the University of South Carolina (ABC@UofSC). Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA), and hearing was evaluated through pure-tone thresholds (PTT) and words-in-noise (WIN) thresholds. White matter integrity was measured with fractional anisotropy (FA) and mean diffusivity (MD), and analyses examined relationships between these DTI metrics and hearing and cognitive scores using the region-of-interest regression analysis. Results showed significant associations between lower FA and higher MD values and poorer hearing and cognitive performance, particularly in the anterior and superior corona radiata, corpus callosum, and superior longitudinal fasciculus. Additionally, ANOVA comparisons between older adults with and without hearing impairments revealed significant MD differences in several regions, indicating specific microstructural changes linked to auditory impairment. This study contributes to the understanding of the neural bases of hearing and cognitive impairments, underscoring the potential of DTI as a complementary tool to gray matter-based studies in exploring reliable imaging evidence of hearing and cognitive impairments in healthy aging across adulthood.

YNICL Journal 2024 Journal Article

Discourse- and lesion-based aphasia quotient estimation using machine learning

Nicholas Riccardi
Satvik Nelakuditi
Dirk B. den Ouden
Chris Rorden
Julius Fridriksson
Rutvik H. Desai

Discourse is a fundamentally important aspect of communication, and discourse production provides a wealth of information about linguistic ability. Aphasia commonly affects, in multiple ways, the ability to produce discourse. Comprehensive aphasia assessments such as the Western Aphasia Battery-Revised (WAB-R) are time- and resource-intensive. We examined whether discourse measures can be used to estimate WAB-R Aphasia Quotient (AQ), and whether this can serve as an ecologically valid, less resource-intensive measure. We used features extracted from discourse tasks using three AphasiaBank prompts involving expositional (picture description), story narrative, and procedural discourse. These features were used to train a machine learning model to predict the WAB-R AQ. We also compared and supplemented the model with lesion location information from structural neuroimaging. We found that discourse-based models could estimate AQ well, and that they outperformed models based on lesion features. Addition of lesion features to the discourse features did not improve the performance of the discourse model substantially. Inspection of the most informative discourse features revealed that different prompt types taxed different aspects of language. These findings suggest that discourse can be used to estimate aphasia severity, and provide insight into the linguistic content elicited by different types of discourse prompts.

YNICL Journal 2024 Journal Article

Progressive lesion necrosis is related to increasing aphasia severity in chronic stroke

Lisa Johnson
Roger Newman-Norlund
Alex Teghipco
Chris Rorden
Leonardo Bonilha
Julius Fridriksson

BACKGROUND: Volumetric investigations of cortical damage resulting from stroke indicate that lesion size and shape continue to change even in the chronic stage of recovery. However, the potential clinical relevance of continued lesion growth has yet to be examined. In the present study, we investigated the prevalence of lesion expansion and the relationship between expansion and changes in aphasia severity in a large sample of individuals in the chronic stage of aphasia recovery. METHODS: Retrospective structural MRI scans from 104 S survivors with at least 2 observations (k = 301 observations; mean time between scans = 31 months) were included. Lesion demarcation was performed using an automated lesion segmentation software and lesion volumes at each timepoint were subsequently calculated. A linear mixed effects model was conducted to investigate the effect of days between scan on lesion expansion. Finally, we investigated the association between lesion expansion and changes on the Western Aphasia Battery (WAB) in a group of participants assessed and scanned at 2 timepoints (N = 54) using a GLM. RESULTS: Most participants (81 %) showed evidence of lesion expansion. The mixed effects model revealed lesion volumes significantly increase, on average, by 0.02 cc each day (7.3 cc per year) following a scan (p < 0.0001). Change on language performance was significantly associated with change in lesion volume (p = 0.025) and age at stroke (p = 0.031). The results suggest that with every 10 cc increase in lesion size, language performance decreases by 0.9 points, and for every 10-year increase in age at stroke, language performance decreases by 1.9 points. CONCLUSIONS: The present study confirms and extends prior reports that lesion expansion occurs well into the chronic stage of stroke. For the first time, we present evidence that expansion is predictive of longitudinal changes in language performance in individuals with aphasia. Future research should focus on the potential mechanisms that may lead to necrosis in areas surrounding the chronic stroke lesion.

YNICL Journal 2023 Journal Article

Brain health imaging markers, post-stroke aphasia and Cognition: A scoping review

Jade Hannan
Janina Wilmskoetter
Julius Fridriksson
Argye E. Hillis
Leonardo Bonilha
Natalie Busby

For the past decade, brain health has been an emerging line of scientific inquiry assessing the impact of age-related neurostructural changes on cognitive decline and recovery from brain injury. Typically, compromised brain health is attributed to the presence of small vessel disease (SVD) and brain tissue atrophy, which are represented by various neuroimaging features. However, to date, the relationship between brain health markers and chronic aphasia severity remains unclear. Thus, the goal of this scoping review was to assess the current body of evidence regarding the relationship between SVD-related brain health biomarkers and post-stroke aphasia and cognition. In all, 187 articles were identified from 3 databases, of which 16 articles met the criteria for inclusion. Among these studies, 11 focused on cognition rather than aphasia, while 2 investigated both. Of the 10 studies that used white matter hyperintensities (WMHs) as an indicator of SVD severity, 8 studies (80%) demonstrated a relationship between WMH load and worse cognition in stroke patients. Interestingly, among the studies that specifically investigated aphasia, all 5 studies (100%) demonstrated a relationship between SVD and worse language performance. They also indicated that factors other than brain health (e.g., lesion, age, time post onset) played an important role in determining aphasia severity at a single timepoint. These findings suggest that brain health is likely a crucial factor in the context of aphasia recovery, possibly indicating the necessity of cognitive reserve thresholds for the multimodal cognitive demands associated with language recovery. While SVD and structural brain health are not commonly considered as predictors of aphasia severity, more comprehensive models incorporating brain health have the potential to improve prognosis of post-stroke cognitive and language deficits. Given the variability in the existing literature, a uniform grading system for overall SVD would be beneficial for future research on the mechanisms related to brain networks and neuroplasticity, and their translational impact.

YNIMG Journal 2022 Journal Article

Functional differentiation in the language network revealed by lesion-symptom mapping

William Matchin
Alexandra Basilakos
Dirk-Bart den Ouden
Brielle C. Stark
Gregory Hickok
Julius Fridriksson

Theories of language organization in the brain commonly posit that different regions underlie distinct linguistic mechanisms. However, such theories have been criticized on the grounds that many neuroimaging studies of language processing find similar effects across regions. Moreover, condition by region interaction effects, which provide the strongest evidence of functional differentiation between regions, have rarely been offered in support of these theories. Here we address this by using lesion-symptom mapping in three large, partially-overlapping groups of aphasia patients with left hemisphere brain damage due to stroke (N = 121, N = 92, N = 218). We identified multiple measure by region interaction effects, associating damage to the posterior middle temporal gyrus with syntactic comprehension deficits, damage to posterior inferior frontal gyrus with expressive agrammatism, and damage to inferior angular gyrus with semantic category word fluency deficits. Our results are inconsistent with recent hypotheses that regions of the language network are undifferentiated with respect to high-level linguistic processing.

YNIMG Journal 2022 Journal Article

Neural correlates of impaired vocal feedback control in post-stroke aphasia

Roozbeh Behroozmand
Leonardo Bonilha
Chris Rorden
Gregory Hickok
Julius Fridriksson

We used left-hemisphere stroke as a model to examine how damage to sensorimotor brain networks impairs vocal auditory feedback processing and control. Individuals with post-stroke aphasia and matched neurotypical control subjects vocalized speech vowel sounds and listened to the playback of their self-produced vocalizations under normal (NAF) and pitch-shifted altered auditory feedback (AAF) while their brain activity was recorded using electroencephalography (EEG) signals. Event-related potentials (ERPs) were utilized as a neural index to probe the effect of vocal production on auditory feedback processing with high temporal resolution, while lesion data in the stroke group was used to determine how brain abnormality accounted for the impairment of such mechanisms. Results revealed that ERP activity was aberrantly modulated during vocalization vs. listening in aphasia, and this effect was accompanied by the reduced magnitude of compensatory vocal responses to pitch-shift alterations in the auditory feedback compared with control subjects. Lesion-mapping revealed that the aberrant pattern of ERP modulation in response to NAF was accounted for by damage to sensorimotor networks within the left-hemisphere inferior frontal, precentral, inferior parietal, and superior temporal cortices. For responses to AAF, neural deficits were predicted by damage to a distinguishable network within the inferior frontal and parietal cortices. These findings define the left-hemisphere sensorimotor networks implicated in auditory feedback processing, error detection, and vocal motor control. Our results provide translational synergy to inform the theoretical models of sensorimotor integration while having clinical applications for diagnosis and treatment of communication disabilities in individuals with stroke and other neurological conditions.

YNICL Journal 2019 Journal Article

Neuroanatomical structures supporting lexical diversity, sophistication, and phonological word features during discourse

Janina Wilmskoetter
Julius Fridriksson
Ezequiel Gleichgerrcht
Brielle C. Stark
John Delgaizo
Gregory Hickok
Kenneth I. Vaden
Argye E. Hillis

Deficits in lexical retrieval are commonly observed in individuals with post-stroke aphasia. Successful lexical retrieval is related to lexical diversity, lexical sophistication, and phonological word properties; however, the crucial brain regions supporting these different features are not fully understood. We performed MRI-based lesion symptom mapping in 58 individuals with a chronic left hemisphere stroke to assess how regional damage relates to spoken discourse-extracted measures of lexical diversity, lexical sophistication, and phonological word properties. For discourse transcription and word feature analysis, we used the Computerized Language Analysis (CLAN) program, Stanford Core Natural Language Processing, Irvine Phonotactic Online Dictionary, Lexical Complexity Analyzer, and Gramulator. Lesions involving the left posterior insula and supramarginal gyri and inferior fronto-occipital fasciculus were significant predictors of utterances with, on average, lower lexical diversity. Low lexical sophistication was associated with damage to the left pole of the superior temporal gyrus. Production of words with lower phonological complexity (fewer phonemes, higher phonological similarity) was associated with damage to the left supramarginal gyrus. Our findings indicate that discourse-extracted features of lexical retrieval depend on the integrity of specific brain regions involving insular and peri-Sylvian areas. The identified regions provide insight into potentially underlying mechanisms of lexically diverse, sophisticated and phonologically complex words produced during discourse.

YNICL Journal 2018 Journal Article

Removal of artifacts from resting-state fMRI data in stroke

Grigori Yourganov
Julius Fridriksson
Brielle Stark
Christopher Rorden

We examined the effect of lesion on the resting-state functional connectivity in chronic post-stroke patients. We found many instances of strong correlations in BOLD signal measured at different locations within the lesion, making it hard to distinguish from the connectivity between intact and strongly connected regions. Regression of the mean cerebro-spinal fluid signal did not alleviate this problem. The connectomes computed by exclusion of lesioned voxels were not good predictors of the behavioral measures. We came up with a novel method that utilizes Independent Component Analysis (as implemented in FSL MELODIC) to identify the sources of variance in the resting-state fMRI data that are driven by the lesion, and to remove this variance. The resulting functional connectomes show better correlations with the behavioral measures of speech and language, and improve the out-of-sample prediction accuracy of multivariate analysis. We therefore advocate this preprocessing method for studies of post-stroke functional connectivity, particularly in samples with large lesions.

YNIMG Journal 2018 Journal Article

Sensorimotor impairment of speech auditory feedback processing in aphasia

Roozbeh Behroozmand
Lorelei Phillip
Karim Johari
Leonardo Bonilha
Chris Rorden
Gregory Hickok
Julius Fridriksson

We investigated the brain network involved in speech sensorimotor processing by studying patients with post-stroke aphasia using an altered auditory feedback (AAF) paradigm. We combined lesion-symptom-mapping analysis and behavioral testing to examine the pervasiveness of speech sensorimotor deficits and their relationship with cortical damage. Sixteen participants with aphasia and sixteen neurologically intact individuals completed a speech task under AAF. The task involved producing speech vowel sounds under the real-time pitch-shifted auditory feedback alteration. This task provided an objective measure for each individual's ability to compensate for mismatch (error) in speech auditory feedback. Results indicated that compensatory speech responses to AAF were significantly diminished in participants with aphasia compared with control. We observed that within the aphasic group, subjects with lower scores on the speech repetition task exhibited greater degree of diminished responses. Lesion-symptom-mapping analysis revealed that the onset phase (50–150 ms) of diminished AAF responses were predicted by damage to auditory cortical regions within the superior and middle temporal gyrus, whereas the rising phase (150–250 ms) and the peak (250–350 ms) of diminished AAF responses were predicted with damage to the inferior frontal gyrus and supramarginal gyrus areas, respectively. These findings suggest that damage to the auditory, motor, and auditory-motor integration networks are associated with impaired sensorimotor function for speech error processing. We suggest that a sensorimotor integration network, as revealed by brain regions related to temporal specific components of AAF responses, is related to speech processing and specific aspects of speech impairment, notably repetition deficits, in individuals with aphasia.

YNICL Journal 2017 Journal Article

Connectome-based lesion-symptom mapping (CLSM): A novel approach to map neurological function

Ezequiel Gleichgerrcht
Julius Fridriksson
Chris Rorden
Leonardo Bonilha

Lesion-symptom mapping is a key tool in understanding the relationship between structure and function in neuroscience as it can provide objective evidence about which regions are crucial for a given process. Initial limitations with this approach were largely overcome by voxel-based lesion-symptom mapping (VLSM), a method introduced in the early 2000s, which allows for a whole-brain approach to study the association between damaged areas and behavioral impairment by applying an independent statistical test at every voxel. By doing so, this technique eliminated the need to predefine regions of interest or classify patients into groups based on arbitrary cutoff scores. VLSM has nonetheless its own limitations; chiefly, a bias towards recognizing cortical necrosis/gliosis but with poor sensitivity for detecting injury along long white matter tracts, thus ignoring cortical disconnection, which can per se lead to behavioral impairment. Here, we propose a complementary method that, instead, establishes a statistical relationship between the strength of connections between all brain regions of the brain (as defined by a standard brain atlas) and the array of behavioral performance seen in patients with brain injury: connectome-based lesion-symptom mapping (CLSM). Whole-brain CLSM therefore has the potential to identify key connections for behavior independently of a priori assumptions with applicability across a broad spectrum of neurological and psychiatric diseases. We propose that this approach can further our understanding of brain-structure relationships and is worth exploring in clinical and theoretical contexts.

YNIMG Journal 2016 Journal Article

Perception drives production across sensory modalities: A network for sensorimotor integration of visual speech

Jonathan H. Venezia
Paul Fillmore
William Matchin
A. Lisette Isenberg
Gregory Hickok
Julius Fridriksson

Sensory information is critical for movement control, both for defining the targets of actions and providing feedback during planning or ongoing movements. This holds for speech motor control as well, where both auditory and somatosensory information have been shown to play a key role. Recent clinical research demonstrates that individuals with severe speech production deficits can show a dramatic improvement in fluency during online mimicking of an audiovisual speech signal suggesting the existence of a visuomotor pathway for speech motor control. Here we used fMRI in healthy individuals to identify this new visuomotor circuit for speech production. Participants were asked to perceive and covertly rehearse nonsense syllable sequences presented auditorily, visually, or audiovisually. The motor act of rehearsal, which is prima facie the same whether or not it is cued with a visible talker, produced different patterns of sensorimotor activation when cued by visual or audiovisual speech (relative to auditory speech). In particular, a network of brain regions including the left posterior middle temporal gyrus and several frontoparietal sensorimotor areas activated more strongly during rehearsal cued by a visible talker versus rehearsal cued by auditory speech alone. Some of these brain regions responded exclusively to rehearsal cued by visual or audiovisual speech. This result has significant implications for models of speech motor control, for the treatment of speech output disorders, and for models of the role of speech gesture imitation in development.

YNICL Journal 2016 Journal Article

Separate neural systems support representations for actions and objects during narrative speech in post-stroke aphasia

Ezequiel Gleichgerrcht
Julius Fridriksson
Chris Rorden
Travis Nesland
Rutvik Desai
Leonardo Bonilha

BACKGROUND: Representations of objects and actions in everyday speech are usually materialized as nouns and verbs, two grammatical classes that constitute the core elements of language. Given their very distinct roles in singling out objects (nouns) or referring to transformative actions (verbs), they likely rely on distinct brain circuits. METHOD: We tested this hypothesis by conducting network-based lesion-symptom mapping in 38 patients with chronic stroke to the left hemisphere. We reconstructed the individual brain connectomes from probabilistic tractography applied to magnetic resonance imaging and obtained measures of production of words referring to objects and actions from narrative discourse elicited by picture naming tasks. RESULTS: Words for actions were associated with a frontal network strongly engaging structures involved in motor control and programming. Words for objects, instead, were related to a posterior network spreading across the occipital, posterior inferior temporal, and parietal regions, likely related with visual processing and imagery, object recognition, and spatial attention/scanning. Thus, each of these networks engaged brain areas typically involved in cognitive and sensorimotor experiences equivalent to the function served by each grammatical class (e.g. motor areas for verbs, perception areas for nouns). CONCLUSIONS: The finding that the two major grammatical classes in human speech rely on two dissociable networks has both important theoretical implications for the neurobiology of language and clinical implications for the assessment and potential rehabilitation and treatment of patients with chronic aphasia due to stroke.

YNIMG Journal 2013 Journal Article

Targeted transcranial direct current stimulation for rehabilitation after stroke

Jacek P. Dmochowski
Abhishek Datta
Yu Huang
Jessica D. Richardson
Marom Bikson
Julius Fridriksson
Lucas C. Parra

Transcranial direct current stimulation (tDCS) is being investigated as an adjunctive technique to behavioral rehabilitation treatment after stroke. The conventional “dosage”, consisting of a large (25cm2) anode over the target with the cathode over the contralateral hemisphere, has been previously shown to yield broadly distributed electric fields whose intensities at the target region are less than maximal. Here, we report the results of a systematic targeting procedure with small “high-definition” electrodes that was used in preparation for a pilot study on 8 stroke patients with chronic aphasia. We employ functional and anatomical magnetic resonance imagery (fMRI/MRI) to define a target and optimize (with respect to the electric field magnitude at the target) the electrode configuration, respectively, and demonstrate that electric field strengths in targeted cortex can be substantially increased (63%) over the conventional approach. The optimal montage exhibits significant variation across subjects as well as when perturbing the target location within a subject. However, for each displacement of the target co-ordinates, the algorithm is able to determine a montage which delivers a consistent amount of current to that location. These results demonstrate that MRI-based models of current flow yield maximal stimulation of target structures, and as such, may aid in reliably assessing the efficacy of tDCS in neuro-rehabilitation.

YNIMG Journal 2012 Journal Article

Age-specific CT and MRI templates for spatial normalization

Christopher Rorden
Leonardo Bonilha
Julius Fridriksson
Benjamin Bender
Hans-Otto Karnath

Spatial normalization reshapes an individual's brain to match the shape and size of a template image. This is a crucial step required for group-level statistical analyses. The most popular standard templates are derived from MRI scans of young adults. We introduce specialized templates that allow normalization algorithms to be applied to stroke-aged populations. First, we developed a CT template: while this is the dominant modality for many clinical situations, there are no modern CT templates and popular algorithms fail to successfully normalize CT scans. Importantly, our template was based on healthy individuals with ages similar to what is commonly seen in stroke (mean 65years old). This template allows studies where only CT scans are available. Second, we derived a MRI template that approximately matches the shape of our CT template as well as processing steps that aid the normalization of scans from older individuals (including lesion masking and the ability to generate high quality cortical renderings despite brain injury). The benefit of this strategy is that the resulting templates can be used in studies where mixed modalities are present. We have integrated these templates and processing algorithms into a simple SPM toolbox (http: //www. mricro. com/clinical-toolbox/spm8-scripts).

YNIMG Journal 2012 Journal Article

Left hemisphere plasticity and aphasia recovery

Julius Fridriksson
Jessica D. Richardson
Paul Fillmore
Bo Cai

A recent study by our group revealed a strong relationship between functional brain changes in the left hemisphere and anomia treatment outcome in chronic stroke patients (N=26) with aphasia (Fridriksson, 2010). The current research represents a continuation of this work in which we have refined our methods and added data from four more patients (for a total sample size of 30) to assess where in the left hemisphere treatment-related brain changes occur. Unlike Fridriksson (2010) which only focused on changes in correct naming as a marker of treatment outcome, the current study examined the relationship between changes in left hemisphere activity and changes in correct naming, semantic paraphasias, and phonemic paraphasias following treatment. We also expanded on the work by Fridriksson by examining whether neurophysiological measures taken at baseline (defined henceforth as the time-point before the start of anomia treatment) predict treatment outcome. Our analyses revealed that changes in activation in perilesional areas predicted treatment-related increases in correct naming in individuals with chronic aphasia. This relationship was most easily observed in the left frontal lobe. A decrease in the number of semantic and phonemic paraphasias was predicted by an activation change in the temporal lobe involving cortical areas that were shown to be active during picture naming in 14 normal subjects. In contrast, a far less certain relationship was found between baseline neurophysiological measures and anomia treatment outcome. Our findings suggest that improved naming associated with behavioral anomia treatment in aphasia is associated with modulation of the left frontal lobe whereas a reduction in naming errors is mediated by left posterior regions that classically are thought to be involved in language processing.

YNIMG Journal 2009 Journal Article

Neural recruitment for the production of native and novel speech sounds

Dana Moser
Julius Fridriksson
Leonardo Bonilha
Eric W. Healy
Gordon Baylis
Julie M. Baker
Chris Rorden

Two primary areas of damage have been implicated in apraxia of speech (AOS) based on the time post-stroke: (1) the left inferior frontal gyrus (IFG) in acute patients, and (2) the left anterior insula (aIns) in chronic patients. While AOS is widely characterized as a disorder in motor speech planning, little is known about the specific contributions of each of these regions in speech. The purpose of this study was to investigate cortical activation during speech production with a specific focus on the aIns and the IFG in normal adults. While undergoing sparse fMRI, 30 normal adults completed a 30-minute speech-repetition task consisting of three-syllable nonwords that contained either (a) English (native) syllables or (b) non-English (novel) syllables. When the novel syllable productions were compared to the native syllable productions, greater neural activation was observed in the aIns and IFG, particularly during the first 10 min of the task when novelty was the greatest. Although activation in the aIns remained high throughout the task for novel productions, greater activation was clearly demonstrated when the initial 10 min was compared to the final 10 min of the task. These results suggest increased activity within an extensive neural network, including the aIns and IFG, when the motor speech system is taxed, such as during the production of novel speech. We speculate that the amount of left aIns recruitment during speech production may be related to the internal construction of the motor speech unit such that the degree of novelty/automaticity would result in more or less demands respectively. The role of the IFG as a storehouse and integrative processor for previously acquired routines is also discussed.

YNIMG Journal 2008 Journal Article

Motor speech perception modulates the cortical language areas

Julius Fridriksson
Joel Moss
Ben Davis
Gordon C. Baylis
Leonardo Bonilha
Chris Rorden

Traditionally, the left frontal and parietal lobes have been associated with language production while regions in the temporal lobe are seen as crucial for language comprehension. However, recent evidence suggests that the classical language areas constitute an integrated network where each area plays a crucial role both in speech production and perception. We used functional MRI to examine whether observing speech motor movements (without auditory speech) relative to non-speech motor movements preferentially activates the cortical speech areas. Furthermore, we tested whether the activation in these regions was modulated by task difficulty. This dissociates between areas that are actively involved with speech perception from regions that show an obligatory activation in response to speech movements (e. g. areas that automatically activate in preparation for a motoric response). Specifically, we hypothesized that regions involved with decoding oral speech would show increasing activation with increasing difficulty. We found that speech movements preferentially activate the frontal and temporal language areas. In contrast, non-speech movements preferentially activate the parietal region. Degraded speech stimuli increased both frontal and parietal lobe activity but did not differentially excite the temporal region. These findings suggest that the frontal language area plays a role in visual speech perception and highlight the differential roles of the classical speech and language areas in processing others' motor speech movements.

YNIMG Journal 2006 Journal Article

Neural recruitment associated with anomia treatment in aphasia

Julius Fridriksson
Leigh Morrow-Odom
Dana Moser
Astrid Fridriksson
Gordon Baylis

The purpose of this study was to investigate changes in the spatial distribution of cortical activity associated with anomia treatment in three persons with aphasia. Participants underwent three fMRI sessions before and after a period of intensive language treatment focused on object naming. The results revealed bilateral hemispheric recruitment associated with improved ability to name items targeted in treatment. This is the first study to employ multiple pre- and post-treatment fMRI sessions in the study of treatment-induced recovery from aphasia and has implications for future studies of brain plasticity in stroke.