Bornali Kundu

Strengthened Effective Connectivity Underlies Transfer of Working Memory Training to Tests of Short-Term Memory and Attention

Although long considered a natively endowed and fixed trait, working memory (WM) ability has recently been shown to improve with intensive training. What remains controversial and poorly understood, however, are the neural bases of these training effects and the extent to which WM training gains transfer to other cognitive tasks. Here we present evidence from human electrophysiology (EEG) and simultaneous transcranial magnetic stimulation and EEG that the transfer of WM training to other cognitive tasks is supported by changes in task-related effective connectivity in frontoparietal and parieto-occipital networks that are engaged by both the trained and transfer tasks. One consequence of this effect is greater efficiency of stimulus processing, as evidenced by changes in EEG indices of individual differences in short-term memory capacity and in visual search performance. Transfer to search-related activity provides evidence that something more fundamental than task-specific strategy or stimulus-specific representations has been learned. Furthermore, these patterns of training and transfer highlight the role of common neural systems in determining individual differences in aspects of visuospatial cognition.

The Unusual Response of Serotonergic Neurons after CNS Injury: Lack of Axonal Dieback and Enhanced Sprouting within the Inhibitory Environment of the Glial Scar

Serotonergic neurons possess an enhanced ability to regenerate or sprout after many types of injury. To understand the mechanisms that underlie their unusual properties, we used a combinatorial approach comparing the behavior of serotonergic and cortical axon tips over time in the same injury environment in vivo and to growth-promoting or growth-inhibitory substrates in vitro. After a thermocoagulatory lesion in the rat frontoparietal cortex, callosal axons become dystrophic and die back. Serotonergic axons, however, persist within the lesion edge. At the third week post-injury, 5-HT+ axons sprout robustly. The lesion environment contains both growth-inhibitory chondroitin sulfate proteoglycans (CSPGs) and growth-promoting laminin. Transgenic mouse serotonergic neurons specifically labeled by enhanced yellow fluorescent protein under control of the Pet-1 promoter/enhancer or cortical neurons were cultured on low amounts of laminin with or without relatively high concentrations of the CSPG aggrecan. Serotonergic neurons extended considerably longer neurites than did cortical neurons on low laminin and exhibited a remarkably more active growth cone on low laminin plus aggrecan during time-lapse imaging than did cortical neurons. Chondroitinase ABC treatment of laminin/CSPG substrates resulted in significantly longer serotonergic but not cortical neurite lengths. This increased ability of serotonergic neurons to robustly grow on high amounts of CSPG may be partially due to significantly higher amounts of growth-associated protein-43 and/or β1 integrin than cortical neurons. Blocking β1 integrin decreased serotonergic and cortical outgrowth on laminin. Determining the mechanism by which serotonergic fibers persist and sprout after lesion could lead to therapeutic strategies for both stroke and spinal cord injury.

Task-dependent changes in cortical excitability and effective connectivity: a combined TMS-EEG study

The brains electrical response to transcranial magnetic stimulation (TMS) is known to be influenced by exogenous factors such as the frequency and intensity of stimulation and the orientation and positioning of the stimulating coil. Less understood, however, is the influence of endogenous neural factors, such as global brain state, on the TMS-evoked response (TMS-ER). In the present study, we explored how changes in behavioral state affect the TMS-ER by perturbing the superior parietal lobule (SPL) with single pulses of TMS and measuring consequent differences in the frequency, strength, and spatial spread of TMS-evoked currents during the delay period of a spatial short-term memory task and during a period of passive fixation. Results revealed that task performance increased the overall strength of electrical currents induced by TMS, increased the spatial spread of TMS-evoked activity to distal brain regions, and increased the ability of TMS to reset the phase of ongoing broadband cortical oscillations. By contrast, task performance had little effect on the dominant frequency of the TMS-ER, both locally and at distal brain areas. These findings contribute to a growing body of work using combined TMS and neuroimaging methods to explore task-dependent changes in the functional organization of cortical networks implicated in task performance.

Impact of Brain Tumor Location on Morbidity and Mortality: A Retrospective Functional MR Imaging Study

These investigators assessed the relationship between the distance of tumor border to eloquent brain regions (motor and language) identified by fMRI and pre- and postoperative morbidity and mortality. Factors that affected patient motor and language presentation and outcomes were close proximity of tumor to functional areas and advanced age. Right-handedness affected only language deficits. Variables that influenced survival included tumor grade, location, and proximity to language and motor areas. These findings indicate that tumors may affect language and motor function differently, depending on tumor lesion to activation distance. Overall, the data support the use of fMRI as a tool to evaluate patient prognosis and are directly applicable to preoperative neurosurgical planning. BACKGROUND AND PURPOSE: fMRI is increasingly used in neurosurgery to preoperatively identify areas of eloquent cortex. Our study evaluated the efficacy of clinical fMRI by analyzing the relationship between the distance from the tumor border to the area of functional activation (LAD) and patient pre- and postoperative morbidity and mortality. MATERIALS AND METHODS: The study included patients with diagnosis of primary or metastatic brain tumor who underwent preoperative fMRI-based motor mapping (n=74) and/or language mapping (n=77). The impact of LAD and other variables collected from patient records was analyzed with respect to functional deficits in terms of morbidity (paresis and aphasia) and mortality. RESULTS: Significant relationships were found between motor and language LAD and the existence of either pre- or postoperative motor (P < .001) and language deficits (P=.009). Increasing age was associated with motor and language deficits (P=.02 and P=.04 respectively). Right-handedness was related to language deficits (P=.05). Survival analysis revealed that pre- and postoperative deficits, grade, tumor location, and LAD predicted mortality. Motor deficits increased linearly as the distance from the tumor to the primary sensorimotor cortex decreased. Language deficits increased exponentially as the distance from the tumor to the language areas decreased below 1 cm. Postoperative mortality analysis showed an interaction effect between motor or language LAD and mortality predictors (grade and tumor location, respectively). CONCLUSIONS: These findings indicate that tumors may affect language and motor function differently depending on tumor LAD. Overall, the data support the use of fMRI as a tool to evaluate patient prognosis and are directly applicable to neurosurgical planning.

Association of functional magnetic resonance imaging indices with postoperative language outcomes in patients with primary brain tumors

OBJECT Functional MRI (fMRI) has the potential to be a useful presurgical planning tool to treat patients with primary brain tumor. In this study the authors retrospectively explored relationships between language-related postoperative outcomes in such patients and multiple factors, including measures estimated from task fMRI maps (proximity of lesion to functional activation area, or lesion-to-activation distance [LAD], and activation-based language lateralization, or lateralization index [LI]) used in the clinical setting for presurgical planning, as well as other factors such as patient age, patient sex, tumor grade, and tumor volume. METHODS Patient information was drawn from a database of patients with brain tumors who had undergone preoperative fMRI-based language mapping of the Broca and Wernicke areas. Patients had performed a battery of tasks, including word-generation tasks and a text-versus-symbols reading task, as part of a clinical fMRI protocol. Individually thresholded task fMRI activation maps had been provided for use in the clinical setting. These clinical imaging maps were used to retrospectively estimate LAD and LI for the Broca and Wernicke areas. RESULTS There was a relationship between postoperative language deficits and the proximity between tumor and Broca area activation (the LAD estimate), where shorter LADs were related to the presence of postoperative aphasia. Stratification by tumor location further showed that for posterior tumors within the temporal and parietal lobes, more bilaterally oriented Broca area activation (LI estimate close to 0) and a shorter Wernicke area LAD were associated with increased postoperative aphasia. Furthermore, decreasing LAD was related to decreasing LI for both Broca and Wernicke areas. Preoperative deficits were related to increasing patient age and a shorter Wernicke area LAD. CONCLUSIONS Overall, LAD and LI, as determined using fMRI in the context of these paradigms, may be useful indicators of postsurgical outcomes. Whereas tumor location may influence postoperative deficits, the results indicated that tumor proximity to an activation area might also interact with how the language network is affected as a whole by the lesion. Although the derivation of LI must be further validated in individual patients by using spatially specific statistical methods, the current results indicated that fMRI is a useful tool for predicting postoperative outcomes in patients with a single brain tumor.

Usage of fMRI for pre-surgical planning in brain tumor and vascular lesion patients: Task and statistical threshold effects on language lateralization

Background and purpose Functional magnetic resonance imaging (fMRI) is a non-invasive pre-surgical tool used to assess localization and lateralization of language function in brain tumor and vascular lesion patients in order to guide neurosurgeons as they devise a surgical approach to treat these lesions. We investigated the effect of varying the statistical thresholds as well as the type of language tasks on functional activation patterns and language lateralization. We hypothesized that language lateralization indices (LIs) would be threshold- and task-dependent. Materials and methods Imaging data were collected from brain tumor patients (n = 67, average age 48 years) and vascular lesion patients (n = 25, average age 43 years) who received pre-operative fMRI scanning. Both patient groups performed expressive (antonym and/or letter-word generation) and receptive (tumor patients performed text-reading; vascular lesion patients performed text-listening) language tasks. A control group (n = 25, average age 45 years) performed the letter-word generation task. Results Brain tumor patients showed left-lateralization during the antonym-word generation and text-reading tasks at high threshold values and bilateral activation during the letter-word generation task, irrespective of the threshold values. Vascular lesion patients showed left-lateralization during the antonym and letter-word generation, and text-listening tasks at high threshold values. Conclusion Our results suggest that the type of task and the applied statistical threshold influence LI and that the threshold effects on LI may be task-specific. Thus identifying critical functional regions and computing LIs should be conducted on an individual subject basis, using a continuum of threshold values with different tasks to provide the most accurate information for surgical planning to minimize post-operative language deficits.

The relationship between carotid artery plaque stability and white matter ischemic injury

Higher local carotid artery strain has previously been shown to be a characteristic of unstable carotid plaques. These plaques may be characterized by microvascular changes that predispose to intraplaque hemorrhage, increasing the likelihood of embolization. Little is known however, about how these strain indices correspond with imaging markers of brain health and metrics of brain structure. White matter hyperintensities (WMHs), which are bright regions seen on T2-weighted brain MRI imaging, are postulated to result from cumulative ischemic vascular injury. Consequently, we hypothesized that plaques that are more prone to microvascular changes and embolization, represented by higher strain indices on ultrasound, would be associated with an increased amount of WMH lesion volume. This relationship would suggest not only emboli as a cause for the brain degenerative changes, but more importantly, a common microvascular etiology for large and small vessel contributions to this process. Subjects scheduled to undergo a carotid endarterectomy were recruited from a neurosurgery clinic. Prior to surgery, participating subjects underwent both ultrasound strain imaging and brain MRI scans as part of a larger clinical study on vascular health and cognition. A linear regression found that maximum absolute strain and peak to peak strain in the surgical side carotid artery were predictive of WMH burden. Furthermore, the occurrence of microembolic signals monitored using transcranial Doppler (TCD) ultrasound examinations also correlated with increasing lesion burden. It is becoming increasingly recognized that cognitive decline is often multifactorial in nature. One contributing extra-brain factor may be changes in the microvasculature that produce unstable carotid artery plaques. In this study, we have shown that higher strain indices in carotid artery plaques are significantly associated with an increased WMH burden, a marker of vascular mediated brain damage.

The role of secondary motor and language cortices in morbidity and mortality: a retrospective functional MRI study of surgical planning for patients with intracranial tumors

OBJECT Functional MRI (fMRI) is commonly used by neurosurgeons preoperatively to identify brain regions associated with essential behaviors, such as language and motor abilities. In this study the authors investigated the relationship between patient morbidity and mortality and the distance from the tumor border area to functional activations in secondary motor and language cortices. METHODS Patients with primary or metastatic brain tumors who underwent preoperative fMRI motor and language mapping were selected from a large database of patients with tumors. The lesion-to-activation distance (LAD) was measured in each patient relative to the supplementary motor area (SMA) for motor tasks and the presupplementary motor area (pSMA) for language tasks. The association between LAD and the incidence of deficits was investigated using the Fisher exact tests of significance. The impact of other variables, including age, handedness, sex, and tumor grade, was also investigated. In a subset of patients, logistic regression was performed to identify the likelihood of deficits based on the LAD to primary and secondary regions. Finally, Mantel-Cox log-rank tests were performed to determine whether survival time was significantly related to the LAD to secondary motor and language areas. RESULTS A significant association was observed between the LAD to the SMA and the incidence of motor deficits, with the percentage of patients with deficits dropping for those in the LAD > 2 cm group. The relationship between the LAD to the pSMA and the incidence of language deficits was not significant. Logistic regression demonstrated that the LAD to primary sensorimotor cortex does affect the incidence of motor deficits, but that the LAD to SMA does not. Finally, the authors observed no relationship between the LAD to secondary regions and patient mortality rates. CONCLUSIONS These results demonstrate that the LAD to SMA structures does affect morbidity, although not to the extent of LAD to primary structures. In addition, motor deficits are significantly associated with LAD to secondary structures, but language deficits are not. This should be considered by neurosurgeons for patient consultation and preoperative planning.

Context-specific differences in fronto-parieto-occipital effective connectivity during short-term memory maintenance

Although visual short-term memory (VSTM) performance has been hypothesized to rely on two distinct mechanisms, capacity and filtering, the two have not been dissociated using network-level causality measures. Here, we hypothesized that behavioral tasks challenging capacity or distraction filtering would both engage a common network of areas, namely dorsolateral prefrontal cortex (dlPFC), superior parietal lobule (SPL), and occipital cortex, but would do so according to dissociable patterns of effective connectivity. We tested this by estimating directed connectivity between areas using conditional Granger causality (cGC). Consistent with our prediction, the results indicated that increasing mnemonic load (capacity) increased the top-down drive from dlPFC to SPL, and cGC in the alpha (8-14Hz) frequency range was a predominant component of this effect. The presence of distraction during encoding (filtering), in contrast, was associated with increased top-down drive from dlPFC to occipital cortices directly and from SPL to occipital cortices directly, in both cases in the beta (15-25Hz) range. Thus, although a common anatomical network may serve VSTM in different contexts, it does so via specific functions that are carried out within distinct, dynamically configured frequency channels.

Intrinsic Hand Muscle Activation for Grasp and Horizontal Transport

During object manipulation, the hand and arm muscles produce internal forces on the object (grasping forces) and forces that result in external translation or rotation of the object in space (transport forces). The present study tested whether the intrinsic hand muscles are actively involved in transport as well as grasping. Intrinsic hand muscle activity increased with increasing demands for grasp stability, but also showed the timing and directional tuning patterns appropriate for actively transmitting external forces to the object, during the translational acceleration and deceleration of object transport