Cognitive brain activity before and after surgery in meningioma patients.

Neuropsychological studies have demonstrated that meningioma patients frequently exhibit cognitive deficits before surgery and show only limited improvement after surgery. Combining neuropsychological with functional imaging measurements can shed more light on the impact of surgery on cognitive brain function. We aimed to evaluate whether surgery affects cognitive brain activity in such a manner that it may mask possible changes in cognitive functioning measured by neuropsychological tests. Twenty-three meningioma patients participated in a fMRI measurement using a verbal working memory task as well as three neuropsychological tests focused on working memory, just before and 3 months after surgery. A region of interest based fMRI analysis was used to examine cognitive brain activity at these timepoints within the central executive network and default mode network. Neuropsychological assessment showed impaired cognitive functioning before as well as 3 months after surgery. Neuropsychological test scores, in-scanner task performance as well as brain activity within the central executive and default mode network were not significantly different between both timepoints. Our results indicate that surgery does not significantly affect cognitive brain activity in meningioma patients the first few months after surgery. Therefore, the lack of cognitive improvement after surgery is not likely the result of compensatory processes in the brain. Cognitive deficits that are already present before surgery appear to be persistent after surgery and a considerable recovery period. Our study shows potential leads that comprehensive cognitive evaluation can be of added value so that cognitive functioning may become a more prominent factor in clinical decision making.

The digital motor output: a conceptual framework for a meaningful clinical performance metric for a motor neuroprosthesis.

In recent years, the majority of the population has become increasingly reliant on continuous and independent control of smart devices to conduct activities of daily living. Upper extremity movement is typically required to generate the motor outputs that control these interfaces, such as rapidly and accurately navigating and clicking a mouse, or activating a touch screen. For people living with tetraplegia, these abilities are lost, significantly compromising their ability to interact with their environment. Implantable brain computer interfaces (BCIs) hold promise for restoring lost neurologic function, including motor neuroprostheses (MNPs). An implantable MNP can directly infer motor intent by detecting brain signals and transmitting the motor signal out of the brain to generate a motor output and subsequently control computer actions. This physiological function is typically performed by the motor neurons in the human body. To evaluate the use of these implanted technologies, there is a need for an objective measurement of the effectiveness of MNPs in restoring motor outputs. Here, we propose the concept of digital motor outputs (DMOs) to address this: a motor output decoded directly from a neural recording during an attempted limb or orofacial movement is transformed into a command that controls an electronic device. Digital motor outputs are diverse and can be categorized as discrete or continuous representations of motor control, and the clinical utility of the control of a single, discrete DMO has been reported in multiple studies. This sets the stage for the DMO to emerge as a quantitative measure of MNP performance.

Online speech synthesis using a chronically implanted brain-computer interface in an individual with ALS.

Recent studies have shown that speech can be reconstructed and synthesized using only brain activity recorded with intracranial electrodes, but until now this has only been done using retrospective analyses of recordings from able-bodied patients temporarily implanted with electrodes for epilepsy surgery. Here, we report online synthesis of intelligible words using a chronically implanted brain-computer interface (BCI) in a clinical trial participant (ClinicalTrials.gov, NCT03567213) with dysarthria due to amyotrophic lateral sclerosis (ALS). We demonstrate a reliable BCI that synthesizes commands freely chosen and spoken by the user from a vocabulary of 6 keywords originally designed to allow intuitive selection of items on a communication board. Our results show for the first time that a speech-impaired individual with ALS can use a chronically implanted BCI to reliably produce synthesized words that are intelligible to human listeners while preserving the participants voice profile.

A functional MRI study of presurgical cognitive deficits in glioma patients.

BACKGROUND: The main goal of this functional MRI (fMRI) study was to examine whether cognitive deficits in glioma patients prior to treatment are associated with abnormal brain activity in either the central executive network (CEN) or default mode network (DMN). METHODS: Forty-six glioma patients, and 23 group-matched healthy controls (HCs) participated in this fMRI experiment, performing an N-back task. Additionally, cognitive profiles of patients were evaluated outside the scanner. A region of interest-based analysis was used to compare brain activity in CEN and DMN between groups. Post hoc analyses were performed to evaluate differences between low-grade glioma (LGG) and high-grade glioma (HGG) patients. RESULTS: In-scanner performance was lower in glioma patients compared to HCs. Neuropsychological testing indicated cognitive impairment in LGG as well as HGG patients. fMRI results revealed normal CEN activation in glioma patients, whereas patients showed reduced DMN deactivation compared to HCs. Brain activity levels did not differ between LGG and HGG patients. CONCLUSIONS: Our study suggests that cognitive deficits in glioma patients prior to treatment are associated with reduced responsiveness of the DMN, but not with abnormal CEN activation. These results suggest that cognitive deficits in glioma patients reflect a reduced capacity to achieve a brain state necessary for normal cognitive performance, rather than abnormal functioning of executive brain regions. Solely focusing on increases in brain activity may well be insufficient if we want to understand the underlying brain mechanism of cognitive impairments in patients, as our results indicate the importance of assessing deactivation.

Automatic identification of atypical clinical fMRI results.

PURPOSE: Functional MRI is not routinely used for neurosurgical planning despite potential important advantages, due to difficulty of determining quality. We introduce a novel method for objective evaluation of fMRI scan quality, based on activation maps. A template matching analysis (TMA) is presented and tested on data from two clinical fMRI protocols, performed by healthy controls in seven clinical centers. Preliminary clinical utility is tested with data from low-grade glioma patients. METHODS: Data were collected from 42 healthy subjects from seven centers, with standardized finger tapping (FT) and verb generation (VG) tasks. Copies of these "typical" data were deliberately analyzed incorrectly to assess feasibility of identifying them as "atypical." Analyses of the VG task administered to 32 tumor patients assessed sensitivity of the TMA method to anatomical abnormalities. RESULTS: TMA identified all atypical activity maps for both tasks, at the cost of incorrectly classifying 3.6 (VG)-6.5% (FT) of typical maps as atypical. For patients, the average TMA was significantly higher than atypical healthy scans, despite localized anatomical abnormalities caused by a tumor. CONCLUSION: This study supports feasibility of TMA for objective identification of atypical activation patterns for motor and verb generation fMRI protocols. TMA can facilitate the use and evaluation of clinical fMRI in hospital settings that have limited access to fMRI experts. In a clinical setting, this method could be applied to automatically flag fMRI scans showing atypical activation patterns for further investigation to determine whether atypicality is caused by poor scan data quality or abnormal functional topography.

Removal of epileptically compromised tissue in the frontal cortex restores oculomotor selection in the antisaccade task.

The frontal cortex is heavily involved in oculomotor selection. Here, we investigated the neural correlates of eye movement selection during an antisaccade task in a young epileptic patient in whom the seizure focus included the frontal cortex and affected its function. Before resection surgery, the patient had difficulty in performing correct antisaccades towards the visual field contralateral to the seizure focus. Because the FEF is the only area in the human frontal cortex that is known to have a lateralized oculomotor function in the antisaccade task, this behavioural imbalance between the two visual fields suggests a disruption of FEF functioning by the nearby seizure focus. Electrocorticographic recordings at the seizure focus indeed showed that the seizure focus interfered with correct antisaccade performance. These results were in line with fMRI recordings revealing less task-related frontal activity for the hemisphere of the seizure focus, possibly reflecting diminished top-down engagement of the oculomotor system. Two months after removal of the compromised tissue, the seizures had disappeared, and antisaccade performance was the same for both visual hemifields. We conclude that a seizure focus in the frontal cortex can induce a dysfunction in the selection of eye movements, which is resolved after removal of interfering tissue.

GridLoc: An automatic and unsupervised localization method for high-density ECoG grids.

Precise localization of electrodes is essential in the field of high-density (HD) electrocorticography (ECoG) brain signal analysis in order to accurately interpret the recorded activity in relation to functional anatomy. Current localization methods for subchronically implanted HD electrode grids involve post-operative imaging. However, for situations where post-operative imaging is not available, such as during acute measurements in awake surgery, electrode localization is complicated. Intra-operative photographs may be informative, but not for electrode grids positioned partially or fully under the skull. Here we present an automatic and unsupervised method to localize HD electrode grids that does not require post-operative imaging. The localization method, named GridLoc, is based on the hypothesis that the anatomical and vascular brain structures under the ECoG electrodes have an effect on the amplitude of the recorded ECoG signal. More specifically, we hypothesize that the spatial match between resting-state high-frequency band power (45-120 Hz) patterns over the grid and the anatomical features of the brain under the electrodes, such as the presence of sulci and larger blood vessels, can be used for adequate HD grid localization. We validate this hypothesis and compare the GridLoc results with electrode locations determined with post-operative imaging and/or photographs in 8 patients implanted with HD-ECoG grids. Locations agreed with an average difference of 1.94 ±â€¯0.11 mm, which is comparable to differences reported earlier between post-operative imaging and photograph methods. The results suggest that resting-state high-frequency band activity can be used for accurate localization of HD grid electrodes on a pre-operative MRI scan and that GridLoc provides a convenient alternative to methods that rely on post-operative imaging or intra-operative photographs.

Inter-hemispheric language functional reorganization in low-grade glioma patients after tumour surgery.

Despite many claims of functional reorganization following tumour surgery, empirical studies that investigate changes in functional activation patterns are rare. This study investigates whether functional recovery following surgical treatment in patients with a low-grade glioma in the left hemisphere is linked to inter-hemispheric reorganization. Based on literature, we hypothesized that reorganization would induce changes in the spatial pattern of activation specifically in tumour homologue brain areas in the healthy right hemisphere. An experimental group (EG) of 14 patients with a glioma in the left hemisphere near language related brain areas, and a control group of 6 patients with a glioma in the right, non-language dominant hemisphere were scanned before and after resection. In addition, an age and gender matched second control group of 18 healthy volunteers was scanned twice. A verb generation task was used to map language related areas and a novel technique was used for data analysis. Contrary to our hypothesis, we found that functional recovery following surgery of low-grade gliomas cannot be linked to functional reorganization in language homologue brain areas in the healthy, right hemisphere. Although elevated changes in the activation pattern were found in patients after surgery, these were largest in brain areas in proximity to the surgical resection, and were very similar to the spatial pattern of the brain shift following surgery. This suggests that the apparent perilesional functional reorganization is mostly caused by the brain shift as a consequence of surgery. Perilesional functional reorganization can however not be excluded. The study suggests that language recovery after transient post-surgical language deficits involves recovery of functioning of the presurgical language system.

Can fMRI safely replace the Wada test for preoperative assessment of language lateralisation? A meta-analysis and systematic review.

Recent studies have shown that fMRI (functional magnetic resonance imaging) may be of value for pre-surgical assessment of language lateralisation. The aim of this study was to systematically review and analyse the available literature. A systematic electronic search for studies comparing fMRI with Wada testing was conducted in the PubMed database between March 2009 and November 2011. Studies involving unilateral Wada testing, study population consisting exclusively of children younger than 12 years of age or involving five patients or fewer were excluded. 22 studies (504 patients) were included. A random effects meta-analysis was conducted to obtain pooled estimates of the positive and negative predictive values of the fMRI using the Wada test as the reference standard. The impact of several study features on the performance of fMRI was assessed. The results showed that 81% of patients were correctly classified as having left or right language dominance or mixed language representation. Techniques were discordant in 19% of patients. fMRI and Wada test agreed in 94% for typical language lateralisation and in 51% for atypical language lateralisation. Language production or language comprehension tasks and different regions of interest did not yield statistically significant different results. It can be concluded that fMRI is reliable when there is strong left-lateralised language. The Wada test is warranted when fMRI fails to show clear left-lateralisation.

Tentative evidence for striatal hyperactivity in adolescent cannabis-using boys: a cross-sectional multicenter fMRI study.

Adolescents' risk-taking behavior has been linked to a maturational imbalance between reward ("go") and inhibitory-control ("stop")-related brain circuitry. This may drive adolescent drug-taking, such as cannabis use. In this study, we assessed the non-acute effects of adolescent cannabis use on reward-related brain function. We performed a two-site (United States and Netherlands; pooled data) functional magnetic resonance imaging (fMRI) study with a cross-sectional design. Twenty-one abstinent but frequent cannabis-using boys were compared with 24 non-using peers on reward-related brain function, using a monetary incentive delay task with fMRI. Focus was on anticipatory and response stages of reward and brain areas critically involved in reward processing like the striatum. Performance in users was normal. Region-of-interest analysis indicated striatal hyperactivity during anticipatory stages of reward in users. Intriguingly, this effect was most pronounced during non-rewarding events. Striatal hyperactivity in adolescent cannabis users may signify an overly sensitive motivational brain circuitry. Frequent cannabis use during adolescence may induce diminished ability to disengage the motivational circuit when no reward can be obtained. This could strengthen the search for reinforcements like drugs of abuse, even when facing the negative (non-rewarding) consequences.

Real-time decoding of brain responses to visuospatial attention using 7T fMRI.

Brain-Computer interface technologies mean to create new communication channels between our mind and our environment, independent of the motor system, by detecting and classifying self regulation of local brain activity. BCIs can provide patients with severe paralysis a means to communicate and to live more independent lives. There has been a growing interest in using invasive recordings for BCI to improve the signal quality. This also potentially gives access to new control strategies previously inaccessible by non-invasive methods. However, before surgery, the best implantation site needs to be determined. The blood-oxygen-level dependent signal changes measured with fMRI have been shown to agree well spatially with those found with invasive electrodes, and are the best option for pre-surgical localization. We show, using real-time fMRI at 7T, that eye movement-independent visuospatial attention can be used as a reliable control strategy for BCIs. At this field strength even subtle signal changes can be detected in single trials thanks to the high contrast-to-noise ratio. A group of healthy subjects were instructed to move their attention between three (two peripheral and one central) spatial target regions while keeping their gaze fixated at the center. The activated regions were first located and thereafter the subjects were given real-time feedback based on the activity in these regions. All subjects managed to regulate local brain areas without training, which suggests that visuospatial attention is a promising new target for intracranial BCI. ECoG data recorded from one epilepsy patient showed that local changes in gamma-power can be used to separate the three classes.

Cortical reorganisation in a preterm born child with unilateral watershed infarction.

In this case report we describe the presence of a unilateral watershed infarction in a preterm born infant. Structural imaging in the neonatal period and in adolescence confirmed a typical lesion pattern compatible with watershed infarction in term born infants. Though the resulting parasagittal cleft transected the primary motor cortex, motor function of the affected hand was relatively spared. Functional MRI and transcranial magnetic stimulation revealed an important role for the unaffected hemisphere in motor control of the affected hand, showing once again that early cortical reorganization may lead to a near normal hand function.

Lateralization of motor innervation in children with intractable focal epilepsy--a TMS and fMRI study.

PURPOSE: To correlate hand function with lateralization of motor innervation, as studied with transcranial magnetic stimulation (TMS) and functional magnetic imaging (fMRI), in children with intractable epilepsy and lesions in the vicinity of the motor cortex. METHODS: In 34 children hand motor function was examined and motor evoked potentials (MEPs) were recorded after TMS of both hemispheres, establishing lateralization of corticospinal innervation. When feasible, patients underwent fMRI using a manual motor task. RESULTS: Good function of the contralesional hand was associated with early lesions (p=0.02). Lateralization of motor innervation to the contralesional hand correlated with quality of motor function (p=0.001); 83% of children with poor hand function had ipsi- or bilateral innervation, whereas all children with good hand function had pure contralateral control. Mirror movements during movement of the unaffected hand predicted ipsilateral contribution to motor innervation (p=0.006). Fourteen children who had no TMS responses were younger than those with elicitable MEPs (p<0.001). TMS led to a temporary increase of seizure frequency in four children. fMRI results were concordant with TMS. CONCLUSIONS: Poor function of the contralesional hand is strongly associated with ipsilateral motor innervation. Reorganization in the lesioned hemisphere mainly occurs in early developmental lesions and seems efficient in maintaining good hand function. Clinical examination of hand function has predictive value for the pattern of motor innervation prior to epilepsy surgery, which in older children can further be established by TMS and fMRI.

Cannabis use and memory brain function in adolescent boys: a cross-sectional multicenter functional magnetic resonance imaging study.

OBJECTIVE: Early-onset cannabis use has been associated with later use/abuse, mental health problems (psychosis, depression), and abnormal development of cognition and brain function. During adolescence, ongoing neurodevelopmental maturation and experience shape the neural circuitry underlying complex cognitive functions such as memory and executive control. Prefrontal and temporal regions are critically involved in these functions. Maturational processes leave these brain areas prone to the potentially harmful effects of cannabis use. METHOD: We performed a two-site (United States and The Netherlands; pooled data) functional magnetic resonance imaging (MRI) study with a cross-sectional design, investigating the effects of adolescent cannabis use on working memory (WM) and associative memory (AM) brain function in 21 abstinent but frequent cannabis-using boys (13-19) years of age and compared them with 24 nonusing peers. Brain activity during WM was assessed before and after rule-based learning (automatization). AM was assessed using a pictorial hippocampal-dependent memory task. RESULTS: Cannabis users performed normally on both memory tasks. During WM assessment, cannabis users showed excessive activity in prefrontal regions when a task was novel, whereas automatization of the task reduced activity to the same level in users and controls. No effect of cannabis use on AM-related brain function was found. CONCLUSIONS: In adolescent cannabis users, the WM system was overactive during a novel task, suggesting functional compensation. Inefficient WM recruitment was not related to a failure in automatization but became evident when processing continuously changing information. The results seem to confirm the vulnerability of still developing frontal lobe functioning for early-onset cannabis use.

The role of functional magnetic resonance imaging in brain surgery.

New functional neuroimaging techniques are changing our understanding of the human brain, and there is now convincing evidence to move away from the classic and clinical static concepts of functional topography. In a modern neurocognitive view, functions are thought to be represented in dynamic large-scale networks. The authors review the current (limited) role of functional MR imaging in brain surgery and the possibilities of new functional MR imaging techniques for research and neurosurgical practice. A critique of current clinical gold standard techniques (electrocortical stimulation and the Wada test) is given.

Chronic effects of cannabis use on the human reward system: an fMRI study.

Cannabis is one of the most used drugs of abuse. It affects the brain reward system in animals, and has proven rewarding and addictive potential in humans. We used functional MRI to measure brain activity during reward anticipation in a monetary reward task. Long-term cannabis users were compared to healthy controls. An additional control group consisting of nicotine users was included. Cannabis users showed attenuated brain activity during reward anticipation in the nucleus accumbens compared to non-smoking controls, but not compared to smoking controls. Cannabis users showed decreased reward anticipation activity in the caudate nucleus, compared to both non-smoking and smoking controls. These data suggest that nicotine may be responsible for attenuated reward anticipation activity in the accumbens, but that differences in the caudate are associated with the use of cannabis. Our findings imply that chronic cannabis use as well as nicotine, may cause an altered brain response to rewarding stimuli.

A practical procedure for real-time functional mapping of eloquent cortex using electrocorticographic signals in humans.

Functional mapping of eloquent cortex is often necessary prior to invasive brain surgery, but current techniques that derive this mapping have important limitations. In this article, we demonstrate the first comprehensive evaluation of a rapid, robust, and practical mapping system that uses passive recordings of electrocorticographic signals. This mapping procedure is based on the BCI2000 and SIGFRIED technologies that we have been developing over the past several years. In our study, we evaluated 10 patients with epilepsy from four different institutions and compared the results of our procedure with the results derived using electrical cortical stimulation (ECS) mapping. The results show that our procedure derives a functional motor cortical map in only a few minutes. They also show a substantial concurrence with the results derived using ECS mapping. Specifically, compared with ECS maps, a next-neighbor evaluation showed no false negatives, and only 0.46 and 1.10% false positives for hand and tongue maps, respectively. In summary, we demonstrate the first comprehensive evaluation of a practical and robust mapping procedure that could become a new tool for planning of invasive brain surgeries.

Assessment of cognitive brain function in ecstasy users and contributions of other drugs of abuse: results from an FMRI study.

Heavy ecstasy use has been associated with neurocognitive deficits in various behavioral and brain imaging studies. However, this association is not conclusive owing to the unavoidable confounding factor of polysubstance use. The present study, as part of the Netherlands XTC Toxicity study, investigated specific effects of ecstasy on working memory, attention, and associative memory, using functional magnetic resonance imaging (fMRI). A large sample (n=71) was carefully composed based on variation in the amount and type of drugs that were used. The sample included 33 heavy ecstasy users (mean 322 pills lifetime). Neurocognitive brain function in three domains: working memory, attention, and associative memory, was assessed with performance measures and fMRI. Independent effects of the use of ecstasy, amphetamine, cocaine, cannabis, alcohol, tobacco, and of gender and IQ were assessed and separated by means of multiple regression analyses. Use of ecstasy had no effect on working memory and attention, but drug use was associated with reduced associative memory performance. Multiple regression analysis showed that associative memory performance was affected by amphetamine much more than by ecstasy. Both drugs affected associative memory-related brain activity, but the effects were consistently in opposite directions, suggesting that different mechanisms are at play. This could be related to the different neurotransmitter systems these drugs predominantly act upon, that is, serotonin (ecstasy) vs dopamine (amphetamine) systems.

Working memory deficits after resection of the dorsolateral prefrontal cortex predicted by functional magnetic resonance imaging and electrocortical stimulation mapping. Case report.

Electrocortical stimulation mapping (ESM) is the clinical standard for localizing critical sensorimotor and language functions, but other functions can be assessed with this technique as well. The authors describe an 8-year-old girl with a left frontal desmoplastic gangliocytoma and medically intractable epilepsy who underwent a chronic invasive recording using electrode grids. Prior to electrode implantation, functional magnetic resonance (fMR) imaging was performed using a research protocol that included a working memory task. The ESM procedure interfered with working memory at a dorsolateral prefrontal site as predicted by fMR imaging, but because this site was part of the epileptogenic region, it was included in the resection. Since the operation the patient has been seizure free and her overall cognitive performance has improved. Yet she shows a selective impairment in working memory tasks that has persisted for over two years, indicating that the area identified using fMR imaging and ESM was critically involved in working memory. Her performance did improve, however, suggesting that compensatory mechanisms took place. This case reveals an important and perhaps critical function of the dorsolateral prefrontal cortex. Work continues to assess the specific cognitive functions subserved by the region identified with fMR imaging and ESM.

Involuntary language switching in two bilingual patients during the Wada test and intraoperative electrocortical stimulation.

We present two bilingual patients without language disorders in whom involuntary language switching was induced. The first patient switched from Dutch to English during a left-sided amobarbital (Wada) test. Functional magnetic resonance imaging yielded a predominantly left-sided language distribution similar for both languages. The second patient switched from French to Chinese during intraoperative electrocortical stimulation of the left inferior frontal gyrus. We conclude that the observed language switching in both cases was not likely the result of a selective inhibition of one language, but the result of a temporary disruption of brain areas that are involved in language switching. These data complement the few lesion studies on (involuntary or unintentional) language switching, and add to the functional neuroimaging studies of switching, monitoring, and controlling the language in use.