Self-referential processes and resting-state connectivity in breast cancer patients before and 1 year after chemotherapy.

Modifications in the processing of information relevant to oneself have been reported in breast cancer (BC) patients. Here, we characterize the longitudinal changes to self-representations in BC patients and how they are related to intrinsic functional brain connectivity. We tested 16 BC patients before (T1) and 1 year after the end of chemotherapy (T2) along with 24 healthy control participants (HC) at similar time points. Participants underwent resting-state fMRI and completed the Questionnaire of Self-Representation (QSR), which evaluates self-assertion and self-esteem. Resting-state functional connectivity (RSFC) was calculated for regions implicated in self-referential processes (dorsomedial prefrontal cortex [dmPFC], posterior cingulate cortex [PCC], and dorsal anterior cingulate cortex [dACC]) and correlated with QSR scores. QSR scores were on average larger in patients compared with HC and did not vary over time. RSFC between the dACC and regions supporting body awareness (precentral/postcentral and supramarginal gyri, superior parietal lobule) decreased more between T1 and T2 in BC patients than in HC. BC patients had lower RSFC than HC between the dmPFC and the PCC, and regions supporting mental imagery (precuneus, lingual gyrus), at each time point, and a greater decrease from T1 and T2. QSR scores negatively correlated with RSFC. Patients described themselves as having greater self-awareness and positive self-image, reflecting a fighting spirit. In parallel, patients presented a decrease in cortical activity related to body awareness and mental imagery of self-representations over time that may be related to the positive self-image patients have and could reflect a temporary adaptive strategy.

Severe Traumatic Brain Injury Patients without Focal Lesion but with Behavioral Disorders: Shrinkage of Gray Matter Nuclei and Thalamus Revealed in a Pilot Voxel-Based MRI Study.

After a traumatic brain injury (TBI), behavioral disorders can occur without major focal brain lesion, and in these situations, their pathophysiology remains unclear. The aim of this study is to examine whether TBI patients with behavioral disorders but without any focal damage, as observed from an initial clinical CT scan, present subtle volumetric alterations that could be measured voxel-by-voxel in the whole brain with MRI. Eight male adults with severe TBI who had behavioral sequela but not major focal cerebral lesion and 17 age-matched controls underwent a volumetric T1-weighted 1.5T MRI. A two step analysis was performed. First, gray matter (GM) and white matter (WM) volumes were compared between groups using voxel-based morphometry. Second, we examined brain regions systematically damaged using the sum of the individual binary maps obtained from z-maps thresholded at -1.75 for significant GM and WM atrophy. TBI patients had lower GM volume than controls (p < 0.001, uncorrected) in the right parahippocampal gyrus; left and right superior, middle, and inferior temporal gyri; left superior frontal gyrus; right middle frontal gyrus; thalami; mammillary bodies; caudate nuclei; insulae; cerebellar cortex; and vermis. WM volume was lower (p < 0.001, uncorrected) in the TBI group than in controls in the periventricular area and around the basal nuclei. We found shrinkage in the dorsomedial thalami in each of the TBI patients, and in the posterior part of the right putamen and caudate nuclei in seven TBI patients. Shrinkage in the dorsomedial thalami and in the posterior part of the right putamen and caudate nuclei may be a common effect of the disseminated microscopic lesions, and be associated with behavioral issues in severe TBI patients without major focal lesions.

Reduced age-associated brain changes in expert meditators: a multimodal neuroimaging pilot study.

Aging is associated with progressive cerebral volume and glucose metabolism decreases. Conditions such as stress and sleep difficulties exacerbate these changes and are risk factors for Alzheimer's disease. Meditation practice, aiming towards stress reduction and emotion regulation, can downregulate these adverse factors. In this pilot study, we explored the possibility that lifelong meditation practice might reduce age-related brain changes by comparing structural MRI and FDG-PET data in 6 elderly expert meditators versus 67 elderly controls. We found increased gray matter volume and/or FDG metabolism in elderly expert meditators compared to controls in the bilateral ventromedial prefrontal and anterior cingulate cortex, insula, temporo-parietal junction, and posterior cingulate cortex /precuneus. Most of these regions were also those exhibiting the strongest effects of age when assessed in a cohort of 186 controls aged 20 to 87 years. Moreover, complementary analyses showed that these changes were still observed when adjusting for lifestyle factors or using a smaller group of controls matched for education. Pending replication in a larger cohort of elderly expert meditators and longitudinal studies, these findings suggest that meditation practice could reduce age-associated structural and functional brain changes.

Episodic future thinking in semantic dementia: a cognitive and FMRI study.

Semantic dementia (SD) is characterized by gradual loss of semantic memory. While episodic autobiographical memory seems relatively preserved, behavioral studies suggest that episodic future thinking is impaired. We used fMRI to measure brain activity in four SD patients (JPL, EP, LL, EG) while they envisioned future events and remembered personal past events. Twelve healthy elders served as controls. Episodic quality, emotion, mental imagery and level of consciousness (via remember/know judgements) were checked at debriefing. We analyzed the future compared to the past for each patient. All patients presented lateral temporal atrophy, but varied in terms of frontal and anterior hippocampal atrophy. Patient JPL presented atrophy in bilateral superior medial frontal gyri and left anterior hippocampus and was unable to engage in episodic future thinking, despite hyperactivations in frontal and occipital regions. Patient EP presented no atrophy in the anterior hippocampus, but atrophy in bilateral superior medial frontal gyrus and had difficulties to engage in episodic future thinking. Patient LL presented atrophy in left anterior hippocampus, but hyperactivated its right counterpart for future compared to past thinking, permitting her to project efficiently in the future in an episodic way. Patient EG presented no atrophy in the superior medial frontal gyri or anterior hippocampi and was able to engage in episodic future thinking. Altogether, patients' future projections differed depending on the severity and localization of their atrophy. The functional integrity of bilateral superior medial frontal gyri and anterior hippocampus appear crucial for episodic future thinking: atrophy of both structures strongly impairs future projection, while integrity of these structures or hyperactivation of residual tissue normalizes episodic future projection.

Autobiographical memory in semantic dementia: new insights from two patients using fMRI.

Episodic autobiographical memory (EAM) consists of personal events embedded within a specific spatiotemporal context. Patients with semantic dementia (SD) generally show preserved recent EAMs, but a controversy remains concerning their ability to retrieve remote ones. Only one fMRI study examined remote autobiographical memory in SD through a longitudinal case study (Maguire, Kumaran, Hassabis, & Kopelman, 2010). Here, we propose a cross-sectional study to test the hippocampo-neocortical up-regulation hypothesis, through a multimodal approach (gray matter volume, activation, connectivity analyses), directly comparing recent and remote autobiographical memory retrieval and collecting data to asses phenomelogical re-experiencing. EAM retrieval recruits a distributed network of brain regions, notably the hippocampus which is shown to be atrophied in SD, although some studies report no hippocampal atrophy in SD. Using fMRI, we examined recent and remote EAM retrieval in two SD patients with different profiles of hippocampal atrophy, compared to 12 healthy elders (HE). JPL presented severe bilateral hippocampal atrophy, while EP showed sparing of both hippocampi. Behaviourally, JPL was impaired at retrieving EAMs from both life periods and showed poorer use of visual mental imagery than HE, while EP retrieved memories which were as episodic as those of HE for both periods and relied on greater use of visual mental imagery than HE. Neuroimaging results showed that, for JPL, hyperactivations of the residual hippocampal tissue and of frontal, lateral temporal, occipital and parietal cortices did not efficiently compensate his autobiographical memory deficit. EP however presented hyperactivations in similar neocortical regions which appeared to be more efficient in compensating for atrophy elsewhere, since EP's EAM retrieval was preserved. Functional connectivity analyses focusing on the hippocampus showed how the residual hippocampal activity was connected to other brain areas. For JPL, recent autobiographical retrieval was associated with connectivity between the posterior hippocampus and middle occipital gyrus, while for EP, connectivity was detected between the anterior hippocampus and numerous regions (medial temporal, occipital, temporal, frontal, parietal) for both recent and remote periods. These findings suggest that intensification of hippocampal atrophy in SD strongly affects both recent and remote autobiographical recollection. Up-regulation of neocortical regions and functional hippocampal-neocortical connectivity within the autobiographical network may be insufficient to compensate the lifelong episodic memory deficit for patients with extensive hippocampal atrophy.

Is neocortical-hippocampal connectivity a better predictor of subsequent recollection than local increases in hippocampal activity? New insights on the role of priming.

During memory encoding, increased hippocampal activity-thought to reflect the binding of different types of information into unique episodes-has been shown to correlate with subsequent recollection of those episodes. Repetition priming-thought to induce more efficient perceptual processing of stimuli-is normally associated with decreased neocortical activity and is often assumed to reduce encoding into episodic memory. Here, we used fMRI to compare activity to primed and unprimed auditory words in the presence of distracting sounds as a function of whether participants subsequently recollected the word-sound associations or only had a feeling of familiarity with the word in a subsequent surprise recognition task. At the behavioral level, priming increased the incidence of subsequent recollection. At the neuronal level, priming reduced activity in the superior temporal gyrus (STG) but also reversed the traditional increase in encoding-related hippocampal activity associated with subsequent recollection relative to subsequent familiarity. To explain this interaction pattern, further analyses using dynamic causal modeling showed an increase in connectivity from left STG to left hippocampus specific to words that were later recollected. These findings show that successful episodic encoding is not determined solely by local hippocampal activity and emphasize instead the importance of increased functional neocortical-hippocampal coupling. Such coupling might be a better predictor of subsequent recollection than the direction of local hippocampal changes per se. We propose that one consequence of priming is to "free up" attentional resources from processing an item in a noisy context, thereby allowing greater attention to encoding of that context.

Autobiographical memory, the sense of recollection and executive functions after severe traumatic brain injury.

Residual disorders of autobiographical memory long after trauma resulting from head injury are rarely assessed, even though they may affect social adjustment and the resumption of daily life. We conducted a thorough study of autobiographical memory in severe traumatic brain injury (TBI) patients, examined at least one year post-trauma. Twenty-five patients were submitted to a novel and controlled autobiographical procedure specially designed to measure episodic memories (i.e., unique, specific in time and space, and detailed) from their entire life span with two kinds of self-remembering experience. The ability to mentally travel back through time and re-experience the source of acquisition, i.e. autonoetic consciousness, was assessed via the "Remember/Know" paradigm and a checking procedure of sense of remembering. Self-perspective in visual imagery, which is also critically involved in episodic recollection, was assessed by the "Field/Observer perspective" paradigm. In addition, the patients underwent a battery of standardized neuropsychological tests to assess episodic and semantic memory, orientation and executive functions. The results showed that the patients, compared with healthy controls, were significantly impaired in recalling episodic autobiographical memories. This impairment was not related to the life period tested or the patients' ages nor the intellectual impairment. Deficits involved disturbances in sense of remembering, visual imagery self-perspective and recollection of spatiotemporal details. Stepwise-regression analyses carried out in the TBI patients revealed a significant relationship between an abnormal sense of remembering and executive dysfunction covering both anterograde and retrograde components. The novel assessment used in this study provides the first detailed evidence of a more fine-grained deficit of autobiographical memory in TBI patients. Indeed, the results suggest that these patients, long after trauma, present autonoetic consciousness and self-perspective disorders, which include sense of identity (the self) as a continuous entity across time, probably related to frontal dysfunction.

The dynamic network subserving the three phases of cognitive procedural learning.

Cognitive procedural learning is characterized by three phases (cognitive, associative, and autonomous), each involving distinct processes. We performed a behavioral study and a positron emission tomography (PET) activation study using the Tower of Toronto task. The aim of the behavioral study was to determine cognitive predictors for the length of each of the three learning phases, in order to preselect subjects for the PET study. The objective of the second study was to describe the cerebral substrates subtending these three phases. Contrasted with a reference (motor) task, the cognitive phase activated the prefrontal cortex, cerebellum, and parietal regions, all of which became less active as learning progressed. The associative phase was characterized by the activation of the occipital regions, right thalamus, and caudate nucleus. During the autonomous phase, new regions were involved, including the left thalamus and an anterior part of the cerebellum. These results, by employing a direct comparison between phases, provide the first evidence of the involvement and the time course of activation of different regions in each learning phase, in accordance with current models of cognitive procedural learning. The involvement of a frontoparietal network suggests the use of strategies in problem solving during the cognitive phase. The involvement of the occipital regions during the associative and autonomous phase suggests the intervention of mental imagery. Lastly, the activation of the cerebellum during the autonomous phase is consistent with the fact that performance in this phase is determined by psychomotor abilities.

Re-experiencing old memories via hippocampus: a PET study of autobiographical memory.

The time-scale of medial temporal lobe (MTL) involvement in storage and retrieval of episodic memory is keenly debated. To test competitive theories of long-term memory consolidation, the present work aimed at characterizing which cerebral regions are involved during retrieval of recent and remote strictly episodic autobiographical memory. Using positron emission tomography (PET), we examined mental retrieval of recent (0-1 year) and remote (5-10 years) autobiographical memories, controlling for the nature of the autobiographical memories (i.e., specificity, state of consciousness, vividness of mental visual imagery, emotion) retrieved during scanning by behavioral measures assessed at debriefing for each event recalled. Cognitive results showed that specificity and emotion did not change with time interval although both autonoetic consciousness and mental image quality were significantly higher for recent memories, suggesting an underlying shift in the phenomenal experience of remembering with the passage of time. The SPM analysis revealed common activations during the recollection of recent and remote memories that involved a widespread but mainly left-sided cerebral network, consistent with previous studies. Subtraction analysis demonstrated that the retrieval of recent (relative to remote) autobiographical memories principally activated the left dorsolateral prefrontal cortex whereas the retrieval of remote (relative to recent) autobiographical memories activated the inferior parietal cortex bilaterally. ROIs analysis revealed more hippocampal activity for remote memories than for recent ones and a preferentially right-sided involvement of the hippocampal responses whatever the remoteness of autobiographical memories. New insights based on higher hippocampal response to the remoteness of episodic autobiographical memories challenge the standard model and are less discrepant with the multiple trace theory.