Nuria Paul

Reorganization of functional connectivity as a correlate of cognitive recovery in acquired brain injury

Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on functional connectivity patterns. Networks were calculated from resting-state magnetoencephalographic recordings from 15 brain injured patients and 14 healthy controls by means of wavelet coherence in standard frequency bands. We compared the parameters defining the network, such as number and strength of interactions as well as their topology, in controls and patients for two conditions: following a traumatic brain injury and after a rehabilitation treatment. A loss of delta- and theta-based connectivity and conversely an increase in alpha- and beta-band-based connectivity were found. Furthermore, connectivity parameters approached controls in all frequency bands, especially in slow-wave bands. A correlation between network reorganization and cognitive recovery was found: the reduction of delta-band-based connections and the increment of those based on alpha band correlated with Verbal Fluency scores, as well as Perceptual Organization and Working Memory Indexes, respectively. Additionally, changes in connectivity values based on theta and beta bands correlated with the Patient Competency Rating Scale. The current study provides new evidence of the neurophysiological mechanisms underlying neuronal plasticity processes after brain injury, and suggests that these changes are related with observed changes at the behavioural level.

Principles of recovery from traumatic brain injury: Reorganization of functional networks

Recovery after brain injury is an excellent platform to study the mechanism underlying brain plasticity, the reorganization of networks. Do complex network measures capture the physiological and cognitive alterations that occurred after a traumatic brain injury and its recovery? Patients as well as control subjects underwent resting-state MEG recording following injury and after neurorehabilitation. Next, network measures such as network strength, path length, efficiency, clustering and energetic cost were calculated. We show that these parameters restore, in many cases, to control ones after recovery, specifically in delta and alpha bands, and we design a model that gives some hints about how the functional networks modify their weights in the recovery process. Positive correlations between complex network measures and some of the general index of the WAIS-III test were found: changes in delta-based path-length and those in Performance IQ score, and alpha-based normalized global efficiency and Perceptual Organization Index. These results indicate that: 1) the principle of recovery depends on the spectral band, 2) the structure of the functional networks evolves in parallel to brain recovery with correlations with neuropsychological scales, and 3) energetic cost reveals an optimal principle of recovery.

Functional Neuroimaging Studies of Cognitive Recovery After Acquired Brain Damage in Adults

The first two decades of cognitive neuroimaging research have provided a constant increase of the knowledge about the neural organization of cognitive processes. Many cognitive functions (e.g.working memory) can now be associated with particular neural structures, and ongoing research promises to clarify this picture further, providing a new mapping between cognitive and neural function. The main goal of this paper is to outline conceptual issues that are particularly important in the context of imaging changes in neural function through recovery process. This review focuses primarily on studies made in stroke and traumatic brain injury patients, but most of the issues raised here are also relevant to studies using other acquired brain damages. Finally, we summarize aset of methodological issues related to functional neuroimaging that are relevant for the study ofneural plasticity and recovery after rehabilitation.

Modulation of brain magnetic activity by different verbal learning strategies

In this study we examined spatiotemporal profiles of brain activity in the context of tasks designed to engage different verbal learning strategies (serial order, phonological, and semantic). The profile of activation associated with the serial-order strategy, which resulted in poor recall performance, featured early activation of the inferior frontal, sensorimotor, and insular region in the left hemisphere, between 200 and 400 ms after stimulus onset. Subsequently, activation was more prominent in dorsolateral prefrontal cortices bilaterally. In contrast, activation profiles associated with the phonological strategy featured predominantly activation of the superior temporal gyrus in the left hemisphere between 500 and 600 ms. Predominant activation of the left middle temporal gyrus, between 500 and 700 ms, was the key feature of the activation profile observed when the semantic elaboration strategy was utilized. These results suggest that different brain circuits are engaged to support learning of new verbal information as a function of the level and type of initial processing applied to the stimuli.

Increased biomagnetic activity in healthy elderly with subjective memory complaints

OBJECTIVE Subjective memory complaints (SMCs) are frequently reported by elderly people with or without objective cognitive impairment (OMI) as assessed by neuropsychological tests. We investigate whether SMCs are associated with altered brain biomagnetic patterns even in the absence of OMI. METHODS We report spatio-temporal patterns of brain magnetic activity recorded with magnetoencephalography during a memory task in 51 elderly participants divided into the following groups: patients with mild cognitive impairment (MCI) with SMC and OMI, individuals with SMC but not OMI, and healthy controls without neither SMC nor OMI. Exclusion criteria for all three groups included a diagnosis of depression or any other psychiatric condition. RESULTS No statistically significant differences were found between MCI patients and participants with SMC. However, the SMC showed higher activation, between 200 and 900 ms after stimulus onset, than the control group in posterior ventral regions and in the dorsal pathway. MCI patients showed higher activation than the control group in the posterior part of the ventral pathway. CONCLUSIONS These findings suggest that similar physiological mechanisms may underlie SMC and MCI, which could be two stages in a cognitive continuum. SIGNIFICANCE MEG provide different neurophysiological profiles between SMC and control subjects.

Alteration and Reorganization of Functional Networks: A New Perspective in Brain Injury Study

Plasticity is the mechanism underlying the brain’s potential capability to compensate injury. Recently several studies have shown how functional connections among the brain areas are severely altered by brain injury and plasticity leading to a reorganization of the networks. This new approach studies the impact of brain injury by means of alteration of functional interactions. The concept of functional connectivity refers to the statistical interdependencies between physiological time series simultaneously recorded in various areas of the brain and it could be an essential tool for brain functional studies, being its deviation from healthy reference an indicator for damage. In this article, we review studies investigating functional connectivity changes after brain injury and subsequent recovery, providing an accessible introduction to common mathematical methods to infer functional connectivity, exploring their capabilities, future perspectives, and clinical uses in brain injury studies.

Early dysfunction of functional connectivity in healthy elderly with subjective memory complaints

It is still an open question whether subjective memory complaints (SMC) can actually be considered to be clinically relevant predictors for the development of an objective memory impairment and even dementia. There is growing evidence that suggests that SMC are associated with an increased risk of dementia and with the presence of biological correlates of early Alzheimers disease. In this paper, in order to shed some light on this issue, we try to discern whether subjects with SMC showed a different profile of functional connectivity compared with subjects with mild cognitive impairment (MCI) and healthy elderly subjects. In the present study, we compare the degree of synchronization of brain signals recorded with magnetoencephalography between three groups of subjects (56 in total): 19 with MCI, 12 with SMC and 25 healthy controls during a memory task. Synchronization likelihood, an index based on the theory of nonlinear dynamical systems, was used to measure functional connectivity. Briefly, results show that subjects with SMC have a very similar pattern of connectivity to control group, but on average, they present a lower synchronization value. These results could indicate that SMC are representing an initial stage with a hypo-synchronization (in comparison with the control group) where the brain system is still not compensating for the failing memory networks, but behaving as controls when compared with the MCI subjects.

Brain activity patterns in stable and progressive mild cognitive impairment during working memory as evidenced by magnetoencephalography.

It has been reported that mild cognitive impairment (MCI) patients, when compared with controls, show increased activity in different brain regions within the ventral pathway during memory tasks. A key question is whether this profile of increased activity could be useful to predict which patients will develop dementia. Herein, we present profiles of brain magnetic activity during a memory task recorded with magnetoencephalography from MCI patients (N = 10), Alzheimers disease (AD) patients (N = 10), and healthy volunteers (N = 17). After 2½ years of follow-up, five of the MCI patients developed AD. Patients who progressed to AD (PMCI) showed higher activity than those who remained stable (SMCI), AD patients and controls. This increased activity in PMCI patients involves regions within the ventral and dorsal pathways. In contrast, SMCI patients showed higher activation than controls only along the ventral pathway. This increase in both the ventral and dorsal pathways in PMCI patients may reflect a compensatory mechanism for the loss in efficiency in memory networks, which would be absent in AD patients as they showed lower activity levels than the rest of the groups.

Prefrontal brain magnetic activity: Effects of memory task demands

Changes in spatiotemporal profiles of brain magnetic activity were investigated in healthy volunteers as a function of varying demands for phonological storage of spoken pseudowords. Greater activity for the phonological memory task was restricted to the dorsolateral prefrontal cortex (DLPFC) in the left hemisphere. During performance of the memory task, activity was initially found in the left superior temporal gyrus (between 100 and 200 ms), followed by activity in the ventrolateral prefrontal, motor, and premotor cortices (between 200 and 300 ms). Activity in DLPFCs was first observed consistently across participants later, between 300 and 400 ms. The data are consistent with the purported role of posterior temporal cortices in phonological analysis and in the online storage of phonological information, the contribution of ventrolateral and motor processing areas in establishment and short-term maintenance of articulatory representations through rehearsal, and the role of DLPFCs in the executive control of the maintenance operation.

Influence of memory strategies on memory test performance: a study in healthy and pathological aging.

ABSTRACT The ability to generate memory strategies is a key factor in the performance of episodic memory tasks. Whether the ability to generate memory strategies exerts an influence in the performance of memory tests in the elderly population is still a matter of debate. Here we present results from an experimental memory task (Test of Memory Strategies, TMS), comprised of five lists of words starting from an incidental learning task, and four more lists which progressively gain in their external organization of the material, reducing the necessity of mobilizing complex memory strategies. TMS has been applied to four groups of elderly patients (amnestic Mild Cognitive Impairment – aMCI, multidomain (mMCI), and Vascular Cognitive Impairment – VCI and Depression) and a healthy aging group. In conditions with low organization of the material, the mMCI and VCI groups (both showing a greater executive function impairment) have shown lower performance. However, as the material was progressively organized, they improved their performance. The aMCI group showed similar performance to the control group at the lower level of external organization but did not improve performance in conditions with a high level of external organization. The mMCI and VCI groups showed lower performance on all TMS conditions compared with controls. Discriminant analysis revealed 90% sensitivity and specificity to differentiate between groups based on TMS conditions. These results indicate how executive functions influence performance on memory tasks in elderly subjects with different neuropsychological profiles.