Lesion‐symptom mapping has become a cornerstone of neuroscience research seeking to localize cognitive function in the brain by examining the sequelae of brain lesions. Recently, multivariate ...lesion‐symptom mapping methods have emerged, such as support vector regression, which simultaneously consider many voxels at once when determining whether damaged regions contribute to behavioral deficits (Zhang, Kimberg, Coslett, Schwartz, & Wang, ). Such multivariate approaches are capable of identifying complex dependences that traditional mass‐univariate approach cannot. Here, we provide a new toolbox for support vector regression lesion‐symptom mapping (SVR‐LSM) that provides a graphical interface and enhances the flexibility and rigor of analyses that can be conducted using this method. Specifically, the toolbox provides cluster‐level family‐wise error correction via permutation testing, the capacity to incorporate arbitrary nuisance models for behavioral data and lesion data and makes available a range of lesion volume correction methods including a new approach that regresses lesion volume out of each voxel in the lesion maps. We demonstrate these new tools in a cohort of chronic left‐hemisphere stroke survivors and examine the difference between results achieved with various lesion volume control methods. A strong bias was found toward brain wide lesion‐deficit associations in both SVR‐LSM and traditional mass‐univariate voxel‐based lesion symptom mapping when lesion volume was not adequately controlled. This bias was corrected using three different regression approaches; among these, regressing lesion volume out of both the behavioral score and the lesion maps provided the greatest sensitivity in analyses.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Purpose: Understanding the brain basis of language and cognitive outcomes is a major goal of aphasia research. Prior studies have not often considered the many ways that brain features can relate to ...behavioral outcomes or the mechanisms underlying these relationships. The purpose of this review article is to provide a new framework for understanding the ways that brain features may relate to language and cognitive outcomes from stroke. Method: Brain-behavior relationships that may be important for aphasia outcomes are organized into a taxonomy, including features of the lesion and features of brain tissue spared by the lesion. Features of spared brain tissue are categorized into those that change after stroke and those that do not. Features that change are further subdivided, and multiple mechanisms of brain change after stroke are discussed. Results: Features of the stroke, including size, location, and white matter damage, relate to many behavioral outcomes and likely account for most of the variance in outcomes. Features of the spared brain tissue that are unchanged by stroke, such as prior ischemic disease in the white matter, contribute to outcomes. Many different neurobiological and behavioral mechanisms may drive changes in the brain after stroke in association with behavioral recovery. Changes primarily driven by neurobiology are likely to occur in brain regions with a systematic relationship to the stroke distribution. Changes primarily driven by behavior are likely to occur in brain networks related to the behavior driving the change. Conclusions: Organizing the various hypothesized brain-behavior relationships according to this framework and considering the mechanisms that drive these relationships may help investigators develop specific experimental designs and more complete statistical models to explain language and cognitive abilities after stroke. Eight main recommendations for future research are provided.
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DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Ten simple rules for neuroimaging meta-analysis Müller, Veronika I.; Cieslik, Edna C.; Laird, Angela R. ...
Neuroscience & biobehavioral reviews/Neuroscience and biobehavioral reviews,
01/2018, Volume:
84
Journal Article
Peer reviewed
Open access
•Meta-analyses require a consistent approach but specific guidelines are lacking.•Best-practice recommendations for conducting neuroimaging meta-analyses are proposed.•We set standards regarding ...which information should be reported for meta-analyses.•The guidelines should improve transparency and replicability of meta-analytic results.
Neuroimaging has evolved into a widely used method to investigate the functional neuroanatomy, brain-behaviour relationships, and pathophysiology of brain disorders, yielding a literature of more than 30,000 papers. With such an explosion of data, it is increasingly difficult to sift through the literature and distinguish spurious from replicable findings. Furthermore, due to the large number of studies, it is challenging to keep track of the wealth of findings. A variety of meta-analytical methods (coordinate-based and image-based) have been developed to help summarise and integrate the vast amount of data arising from neuroimaging studies. However, the field lacks specific guidelines for the conduct of such meta-analyses. Based on our combined experience, we propose best-practice recommendations that researchers from multiple disciplines may find helpful. In addition, we provide specific guidelines and a checklist that will hopefully improve the transparency, traceability, replicability and reporting of meta-analytical results of neuroimaging data.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Aphasia is a common consequence of left hemisphere stroke and causes a disabling loss of language and communication ability. Current treatments for aphasia are inadequate, leaving a majority of ...aphasia sufferers with ongoing communication difficulties for the rest of their lives. In the past decade, two forms of noninvasive brain stimulation, repetitive transcranial magnetic stimulation and transcranial direct current stimulation, have emerged as promising new treatments for aphasia. The most common brain stimulation protocols attempt to inhibit the intact right hemisphere based on the hypothesis that maladaptive activity in the right hemisphere limits language recovery in the left. There is now sufficient evidence to demonstrate that this approach, at least for repetitive transcranial magnetic stimulation, improves specific language abilities in aphasia. However, the biological mechanisms that produce these behavioral improvements remain poorly understood. Taken in the context of the larger neurobiological literature on aphasia recovery, the role of the right hemisphere in aphasia recovery remains unclear. Additional research is needed to understand biological mechanisms of recovery, in order to optimize brain stimulation treatments for aphasia. This article summarizes the current evidence on noninvasive brain stimulation methods for aphasia and the neuroscientific considerations surrounding treatments using right hemisphere inhibition. Suggestions are provided for further investigation and for clinicians whose patients ask about brain stimulation treatments for aphasia.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Sequence learning underlies numerous motor, cognitive, and social skills. Previous models and empirical investigations of sequence learning in humans and non-human animals have implicated ...cortico-basal ganglia-cerebellar circuitry as well as other structures. To systematically examine the functional neuroanatomy of sequence learning in humans, we conducted a series of neuroanatomical meta-analyses. We focused on the serial reaction time (SRT) task. This task, which is the most widely used paradigm for probing sequence learning in humans, allows for the rigorous control of visual, motor, and other factors. Controlling for these factors (in sequence-random block contrasts), sequence learning yielded consistent activation only in the basal ganglia, across the striatum (anterior/mid caudate nucleus and putamen) and the globus pallidus. In contrast, when visual, motor, and other factors were not controlled for (in a global analysis with all sequence-baseline contrasts, not just sequence-random contrasts), premotor cortical and cerebellar activation were additionally observed. The study provides solid evidence that, at least as tested with the visuo-motor SRT task, sequence learning in humans relies on the basal ganglia, whereas cerebellar and premotor regions appear to contribute to aspects of the task not related to sequence learning itself. The findings have both basic research and translational implications.
•Using ALE, we synthesized the functional neuroanatomical data on sequence learning.•We focused on the widely used serial reaction time (SRT) task paradigm.•Sequence learning (sequence > random contrast) showed only basal ganglia activation.•This was found in the anterior/mid caudate and putamen, and in the globus pallidus.•Cerebellar/premotor activation was linked to other (visual/motor) SRT task factors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
It has been proposed that the cerebellum acquires internal models of mental processes that enable prediction, allowing for the optimization of behavior. In language, semantic prediction speeds speech ...production and comprehension. Right cerebellar lobules VI and VII (including Crus I/II) are engaged during a variety of language processes and are functionally connected with cerebral cortical language networks. Further, right posterolateral cerebellar neuromodulation modifies behavior during predictive language processing. These data are consistent with a role for the cerebellum in semantic processing and semantic prediction. We combined transcranial direct current stimulation (tDCS) and fMRI to assess the behavioral and neural consequences of cerebellar tDCS during a sentence completion task. Task-based and resting-state fMRI data were acquired in healthy human adults (
= 32; μ = 23.1 years) both before and after 20 min of 1.5 mA anodal (
= 18) or sham (
= 14) tDCS applied to the right posterolateral cerebellum. In the sentence completion task, the first four words of the sentence modulated the predictability of the final target word. In some sentences, the preceding context strongly predicted the target word, whereas other sentences were nonpredictive. Completion of predictive sentences increased activation in right Crus I/II of the cerebellum. Relative to sham tDCS, anodal tDCS increased activation in right Crus I/II during semantic prediction and enhanced resting-state functional connectivity between hubs of the reading/language networks. These results are consistent with a role for the right posterolateral cerebellum beyond motor aspects of language, and suggest that cerebellar internal models of linguistic stimuli support semantic prediction.
Cerebellar involvement in language tasks and language networks is now well established, yet the specific cerebellar contribution to language processing remains unclear. It is thought that the cerebellum acquires internal models of mental processes that enable prediction, allowing for the optimization of behavior. Here we combined neuroimaging and neuromodulation to provide evidence that the cerebellum is specifically involved in semantic prediction during sentence processing. We found that activation within right Crus I/II was enhanced when semantic predictions were made, and we show that modulation of this region with transcranial direct current stimulation alters both activation patterns and functional connectivity within whole-brain language networks. For the first time, these data show that cerebellar neuromodulation impacts activation patterns specifically during predictive language processing.
Language learning as an adult, though often difficult, is quite common. Nevertheless, the neural substrates of this process remain unclear, even though identifying them should clarify how language is ...learned and could lead to improved success at this endeavor. We addressed this gap by conducting multiple neuroanatomical meta-analyses to synthesize the functional neuroimaging literature of language learning. We focused on learning lexical and grammatical knowledge, two building blocks of language. Lexical and grammatical learning yielded overlapping activation in frontal (e.g., BA 44/45) and posterior parietal regions. Only lexical learning showed ventral occipito-temporal (ventral stream) activation, while only grammatical learning showed basal ganglia (anterior caudate/putamen) activation. To further elucidate the neurocognition of grammar learning, we also tested specific predictions of the declarative/procedural model of language. Consistent with the model, grammar learning predicted to rely especially on declarative memory (e.g., with explicit training) showed hippocampal involvement, while grammar learning predicted to rely particularly on procedural memory (e.g., with implicit training) showed anterior caudate/putamen involvement. Finally, given the prevalence of research on artificial grammars, we performed separate analyses of artificial grammar and non-artificial grammar (e.g., miniature language) paradigms. These yielded overlapping activation, especially in BA 44, underscoring the validity of artificial grammars as models for grammar learning in natural languages. In sum, the study elucidates the empirical and theoretical landscape of language learning and has applied implications.
•Using ALE, we synthesized the functional neuroanatomical data on language learning.•Lexicon and grammar showed frontal (IFG & nearby) and posterior parietal activation.•Only lexicon activated the ventral steam; only grammar activated the basal ganglia.•Grammar activated either MTL or basal ganglia, depending on context and stimuli.•Overlap in BA 44 was found for artificial grammar and more natural grammar learning.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Highlights • This article reports on the safety of transcranial Direct Current Stimulation (tDCS), based on published Serious Adverse Effects in human trials and irreversible brain damage in animal ...models • Doses of tDCS sessions are defined and categorized by the electrode montage (skin contact area/size and position of all electrodes), stimulation intensity and duration • To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 mA, ≤7.2 C) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1,000 subjects with repeated sessions
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The lesion method has been important for understanding brain-behavior relationships in humans, but has previously used maps based on structural damage. Lesion measurement based on structural damage ...may label partly damaged but functional tissue as abnormal, and moreover, ignores distant dysfunction in structurally intact tissue caused by deafferentation, diaschisis, and other processes. A reliable method to map functional integrity of tissue throughout the brain would provide a valuable new approach to measuring lesions. Here, we use machine learning on four dimensional resting state fMRI data obtained from left-hemisphere stroke survivors in the chronic period of recovery and control subjects to generate graded maps of functional anomaly throughout the brain in individual patients. These functional anomaly maps identify areas of obvious structural lesions and are stable across multiple measurements taken months and even years apart. Moreover, the maps identify functionally anomalous regions in structurally intact tissue, providing a direct measure of remote effects of lesions on the function of distant brain structures. Multivariate lesion-behavior mapping using functional anomaly maps replicates classic behavioral localization, identifying inferior frontal regions related to speech fluency, lateral temporal regions related to auditory comprehension, parietal regions related to phonology, and the hand area of motor cortex and descending corticospinal pathways for hand motor function. Further, this approach identifies relationships between tissue function and behavior distant from the structural lesions, including right premotor dysfunction related to ipsilateral hand movement, and right cerebellar regions known to contribute to speech fluency. Brain-wide maps of the functional effects of focal lesions could have wide implications for lesion-behavior association studies and studies of recovery after brain injury.
•A new method, “functional anomaly mapping,” is developed to estimate whole-brain, voxelwise maps of abnormal spontaneous BOLD fluctuations for individual patients with stroke from resting fMRI•Functional anomaly mapping signal is validated to index functional integrity of spared tissue as well as to detect areas of frank structural lesion•Test-retest reliability of functional anomaly mapping is established to be good-to-excellent•An application to lesion-behavioral mapping is illustrated for functional anomaly mapping
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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