Dissociated pathways for successful memory retrieval from the human parietal cortex: anatomical and functional connectivity analyses.

Imaging of Eating Disorders: Multiple Techniques to Demonstrate the Dynamic Brain

There is substantial overlap between the brain regions supporting episodic memory and the default network. However, in humans, the impact of bilateral medial temporal lobe (MTL) damage on a large-scale neural network such as the default mode network is unknown. To examine this issue, resting fMRI was performed with amnesic patients and control participants. Seed-based functional connectivity analyses revealed robust default network connectivity in amnesia in cortical default network regions such as medial prefrontal cortex, posterior medial cortex, and lateral parietal cortex, as well as evidence of connectivity to residual MTL tissue. Relative to control participants, decreased posterior cingulate cortex connectivity to MTL and increased connectivity to cortical default network regions including lateral parietal and medial prefrontal cortex were observed in amnesic patients. In contrast, somatomotor network connectivity was intact in amnesic patients, indicating that bilateral MTL lesions may selectively impact the default network. Changes in default network connectivity in amnesia were largely restricted to the MTL subsystem, providing preliminary support from MTL amnesic patients that the default network can be fractionated into functionally and structurally distinct components. To our knowledge, this is the first examination of the default network in amnesia.

Visual attention can be primarily allocated to either where an object is in space (with little emphasis on the structure of the object itself) or to the structure of the object (with little emphasis on where in space the object is located). Using PET measures of regional cerebral blood flow (rCBF) to index neural activity, we investigated the shared and specific functional anatomy underlying both of these types of visual attention in a controlled non-cueing non-blocked paradigm that involved identical stimuli across the conditions of interest. The interaction of eye movements with these attentional systems was studied by introducing fixation or free vision as an additional factor. Relative to the control condition, object-based and space-based attention showed significant activations of the left and right medial superior parietal cortex and the left lateral inferior parietal cortex, the left prefrontal cortex and the cerebellar vermis. Significant differential activations were observed during object-based attention in the left striate and prestriate cortex. Space-based attention activated the right prefrontal cortex and the right inferior temporal-occipital cortex. Differential neural activity due to free vision or fixation was observed in occipital areas only. Significant interactions of free vision/fixation on activations due to object-based and space-based attention were observed in the right medial superior parietal cortex and left lateral inferior parietal cortex, respectively. The study provides direct evidence for the importance of the parietal cortex in the control of object-based and space-based visual attention. The results show that object-based and space-based attention share common neural mechanisms in the parietal lobes, in addition to task specific mechanisms in early visual processing areas of temporal and occipital cortices.

Only one large series using statistical parametric mapping (SPM) reports on FDG-PET in sporadic (Heidenhain and non-Heidenhain variant) Creutzfeldt-Jakob disease (sCJD), describing hypometabolism in bilateral parietal, frontal, and occipital cortices. Our aim was to study FDG-PET in non-Heidenhain probable sCJD patients in order to assess the most pertinent FDG-PET pattern, and to compare FDG-PET and MRI data. We used both SPM and NeuroGam(®) software analysis, compared with healthy controls, to describe the FDG-PET abnormalities. Individual FDG-PET and MRI-DWI data were compared. SPM group analysis showed lateralized hypometabolism in the medial parietal cortex, the lateral and medial frontal (sparing Brodmann's area 4 and 6 and the anterior cingulate cortex), and lateral parietal cortex, in the absence of basal ganglia or cerebellar hypometabolism. The most severe hypometabolism was seen in Brodmann's area 31, and to a lesser degree area 23 (both areas correspond to the posterior cingulate cortex) and the precuneus. On individual analysis using NeuroGam(®) software, additional variable temporal cortex and frequent basal ganglia (with caudate nucleus as the most frequently involved structure) hypometabolism was seen, in the absence of cerebellar hypometabolism. The cerebral lobe cortex was more frequently and more severely hypometabolic than basal ganglia structures. Concordance between FDG-PET and MRI abnormalities was most often present for both the cerebral lobe cortex and the basal ganglia. In the case of discordance, FDG-PET was more sensitive than MRI for the cortex, whereas MRI was more sensitive than FDG-PET for the basal ganglia. When pathological, both cortical lobe cortex and basal ganglia involvement were slightly more often lateralized on FDG-PET than on MRI. Despite the presence of overlapping features with other diseases presenting with rapidly progressive dementia, the FDG-PET pattern we found in our non-Heidenhain sCJD patients may help in the differential diagnosis of rapidly progressive dementia.

Decades of research have highlighted the importance of lateral parietal cortex (LPC) across a myriad of cognitive domains. Yet, the underlying function of LPC remains unclear. Two domains that have emphasized LPC involvement are semantic memory and episodic memory retrieval. From each domain, sophisticated functional models have been proposed, as well as the more domain-general assumption that LPC is engaged by any form of internally directed cognition (episodic/semantic retrieval being examples). Here we used a combination of functional magnetic resonance imaging, functional connectivity, and diffusion tensor imaging white-matter connectivity to show that (i) ventral LPC (angular gyrus [AG]) was positively engaged during episodic retrieval but disengaged during semantic memory retrieval and (ii) activity negatively varied with task difficulty in the semantic task whereas episodic activation was independent of difficulty. In contrast, dorsal LPC (intraparietal sulcus) showed domain general activation that was positively correlated with task difficulty. Finally, (iii) a dorsal–ventral and anterior–posterior gradient of functional and structural connectivity was found across the AG (e.g. mid-AG connected with episodic retrieval). We propose a unifying model in which LPC as a whole might share a common underlying neurocomputation (multimodal buffering) with variations in the emergent cognitive functions across subregions arising from differences in the underlying connectivity.

Metamemory refers to knowledge and monitoring of one's own memory. Metamemory monitoring can be done prospectively with respect to subsequent memory retrieval or retrospectively with respect to previous memory retrieval. In this study, we used fMRI to compare neural activity during prospective feeling-of-knowing and retrospective confidence tasks in order to examine common and distinct mechanisms supporting multiple forms of metamemory monitoring. Both metamemory tasks, compared to non-metamemory tasks, were associated with greater activity in medial prefrontal, medial parietal, and lateral parietal regions, which have previously been implicated in internally directed cognition. Furthermore, compared to non-metamemory tasks, metamemory tasks were associated with less activity in occipital regions, and in lateral inferior frontal and dorsal medial prefrontal regions, which have previously shown involvement in visual processing and stimulus-oriented attention, respectively. Thus, neural activity related to metamemory is characterized by both a shift toward internally directed cognition and away from externally directed cognition. Several regions demonstrated differences in neural activity between feeling-of-knowing and confidence tasks, including fusiform, medial temporal lobe, and medial parietal regions; furthermore, these regions also showed interaction effects between task and the subjective metamemory rating, suggesting that they are sensitive to the information monitored in each particular task. These findings demonstrate both common and distinct neural mechanisms supporting metamemory processes and also serve to elucidate the functional roles of previously characterized brain networks.

BackgroundAlzheimer’s disease (AD)‐related pathology (i.e., amyloid‐β and neurofibrillary tangles) disrupts functional networks that support higher‐order cognitive functions. Yet, it is not well known how the brain’s functional architecture is differentially associated with in vivo pathology in preclinical AD, which is critical for predicting disease risk and progression. We intersected functional connectivity and PET images to examine how in vivo amyloid‐β and tau pathologies are associated with weighted‐degree centrality patterns, known to be important for understanding network organization and information transmission hubs, in cognitively‐unimpaired individuals with autosomal‐dominant AD due to the Presenilin‐1 (PSEN‐1) E280A mutation.Method21 cognitively‐unimpaired PSEN1 E280A carriers and 31 non‐carriers underwent resting‐state fMRI, 11C Pittsburgh compound B‐PET and 18F Flortaucipir‐PET. We used graph‐based network analyses to examine weighted‐degree centrality, the sum of weights from edges connecting to a node. A general linear model was used to compare connectivity maps between groups, and partial correlations were used to examine the relationship between individual‐subject maps with whole‐brain amyloid‐β and tau PET. A significance threshold of p<0.05 was used. Analyses were covaried for age and corrected for multiple comparisons.ResultCompared to non‐carriers, mutation carriers exhibited reduced weighted‐degree in the medial occipitoparietal and posterior cingulate cortices. Greater amyloid‐β was associated with reduced weighted‐degree in the lateral temporal lobe and fusiform gyrus, and greater weighted‐degree in the lateral and medial prefrontal cortices. In turn, greater tau burden was associated with greater weighted‐degree in the lateral and medial temporal regions, anterior and posterior cingulate cortices, lateral parietal cortex and precuneus, and decreased weighted‐degree in dorsomedial prefrontal cortex.ConclusionOur findings show that cognitively‐unimpaired individuals who are genetically‐determined to develop AD dementia in their forties have abnormal patterns of functional connectivity that resemble spatial patterns of amyloid‐β and tau propagation. Regions that had weaker connections with nearby and distant regions showed greater amyloid‐β burden, while regions that were highly functionally connected exhibited greater tau burden, which has been suggested to increase the probability of tau seeding and propagation. These findings contribute to our understanding of how functional connectivity patterns can help predict risk and monitor AD progression from preclinical to clinical stages.

Impaired functional default mode network in patients with mild neurological Wilson’s disease

N-acetylaspartate (NAA) in the medial temporal lobe (MTL) and parietal lobe gray matter (GM) is diminished in Alzheimer disease (AD). Because NAA is considered a marker of neuronal integrity, reduced medial temporal and parietal lobe NAA could be an early indication of dementia-related pathology in elderly individuals. 1) To determine whether cognitively impaired but nondemented (CIND) elderly individuals exhibit a similar pattern of reduced medial temporal and parietal lobe NAA as AD patients. 2) To compare regional NAA patterns, hippocampal and neocortical gray matter (GM) volumes in CIND patients who remained cognitively stable and those who became demented over 3.6 years of follow-up. 3) To examine the relationship between memory performance, medial temporal lobe NAA, and hippocampal volume. Seventeen CIND, 24 AD, and 24 cognitively normal subjects were studied using MRSI and MRI. Relative to controls, CIND patients had reduced MTL NAA (19 to 21%, p = 0.005), hippocampal (11 to 14%, p < or = 0.04), and neocortical GM (5%, p = 0.05) volumes. CIND patients who later became demented had less MTL NAA (26%, p = 0.01), hippocampal (17 to 23%, p < or = 0.05), and neocortical GM (13%, p = 0.02) volumes than controls, but there were no significant differences between stable CIND patients and controls. MTL NAA in combination with hippocampal volume improved discrimination of CIND and controls over hippocampal volume alone. In AD and CIND patients, decreased MTL NAA correlated significantly with impaired memory performance. Reduced medial temporal lobe N-acetylaspartate, together with reduced hippocampal and neocortical gray matter volumes, may be early indications of dementia-related pathology in subjects at high risk for developing dementia.

This article investigates the functional connectivity patterns of the nucleus accumbens (NAcc) in 18 healthy participants using a resting state functional connectivity (rsFC) protocol. Also, a meta-analytic connectivity modeling (MACM) was used to characterize patterns of functional coactivations involving NAcc: The results of a structure-based meta-analyses of 57 fMRI and PET studies were submitted to activation likelihood estimation analysis to estimate consistent activation patterns across the different imaging studies. The results of the combined rsFC and MACM analyses show that spontaneous activity in NAcc predicts activity in regions implicated in reward circuitries, including orbitomedial prefrontal cortex, globus pallidus, thalamus, midbrain, amygdala, and insula. This confirms the key role of NAcc in the mesocorticolimbic system, which integrates inputs from limbic and cortical regions. We also detected activity in brain regions having few or no direct anatomical connections with NAcc, such as sensorimotor cortex, cerebellum, medial and posterior parietal cortex, and medial/inferior temporal cortex, supporting the view that not all functional connections can be explained by anatomical connections but can also result from connections mediated by third areas. Our rsFC findings are in line with the results of the structure-based meta-analysis: MACM maps are superimposable with NAcc rsFC results, and the reward paradigm class is the one that most frequently generates activation in NAcc. Our results overlap considerably with recently proposed schemata of the main neuron systems in the limbic forebrain and in the anterior part of the limbic midbrain in rodents and nonhuman primates.

Review of: Watrous AJ, Tandon N, Conner CR, Pieters T, Ekstrom AD. Frequency-specific network connectivity increases underlie accurate spatiotemporal memory retrieval. Nat Neurosci 2013 doi:10.1038/nn.3315. Humans depend on a memory system to rapidly and veraciously store the massive stream of incoming information documenting their experiences, and faithfully represent and recall that information for future use. Devastating dysfunction in the system is observed in schizophrenia and Alzheimer’s disease. While the medial temporal lobe (MTL), prefrontal cortex (PFC), and parietal lobe have been implicated in an episodic memory retrieval network, the processes underlying successful retrieval remain undetermined, particularly regarding simultaneous recall of different classes of information represented by shared neuronal ensembles. Leading hypotheses propose that retrieval may be defined by changes in connectivity and activity of one region in the network, connections throughout the network, or phase-synchronized activity at specific frequencies. In a recent study, Watrous et al. tested these theories with simultaneous electrocortigraphical (ECoG) recordings from these regions during episodic memory retrieval. Six patients with medically intractable epilepsy underwent invasive monitoring, and the derived data were used for this study. Electrodes were localized to subregions of the MTL, PFC, and parietal cortex. Patients performed a spatiotemporal memory-dependent task with a virtual taxi game, in which they drove passengers to five irregularly spaced stores in a specific sequential order. Once patients reached criteria levels of accuracy or training time, retrieval of spatial and temporal information was tested separately. Phase synchronization was utilized as a measure of functional connectivity to test the different hypotheses. Pairwise phase consistency (PPC) index, which is based on phase angle difference between signals from different electrodes, was used to quantify the phase synchronization across electrode pairs. Two subregions, termed nodes within the network, were considered functionally connected when the PPC between them differed significantly depending on the condition (correct vs. incorrect responses, spatial vs. temporal memory retrieval). The node degree, a node’s total number of connections, also marked the magnitude of connectivity. Nodes with the highest node degree were defined as hubs. With the greatest connectivity, a hub is thought to play a central role in mediating interactions across the network for retrieval. The percent connectivity was also calculated as the number of connections a node has in a given condition out of the total possible connections. The authors found that functional connectivity, derived by measuring phase-synchronized low-frequency oscillations, was augmented both globally and in the parahippocampal gyrus (PHG) with successful retrieval of spatiotemporal memory. PPC of delta-theta frequency (1-10 Hz) range was greater for correct responses than incorrect. While percent connectivity increased throughout the network with successful retrieval, a disproportionately greater increase in the PHG node was also observed. PHG was designated a hub in the retrieval network. According to these findings, both network-wide and regional, but not frequency-specific, increases in functional connectivity occur for retrieval of spatiotemporal information. Comparing spatial versus temporal memory retrieval uncovered spectral, temporal, and regional segregation of functional connectivity within the retrieval network. For retrieval of spatial information, PPC and percent connectivity were increased between PHG, superior frontal gyrus (SFG), and middle frontal gyrus (MFG), and precuneus areas, at 1-4 Hz, and early in memory retrieval. Temporal memory retrieval was characterized by greater PPC and percent connectivity between PHG, SFG, MFG, and the inferior parietal lobule, at 7-10 Hz, and later in memory retrieval. The PHG was a hub in both conditions, making the same number of overall connections with other nodes, and with differential clustering of connectivity (Figure 1).Figure 1: Frequency-specific synchronization occurs among several components of the human memory system during context retrieval. (G-J) Correct spatial and temporal retrieval networks (within the context of the virtual taxi game task) in the 1–4-Hz and 7–10-Hz bands.This work has notable implications for neuroscience and neurosurgery. The role of mesial temporal lobe structures (particularly the hippocampus) in memory recall remains controversial, particularly after memory consolidation. The hippocampus’s role in memory encoding is well established. Theories of consolidation typically argue that retrieval of consolidated information is independent of the hippocampus, while the Multiple Trace Theory (MTT) proposes that memory recall is hippocampus-dependent. The identification of the PHG, which is intimately connected with the hippocampus, as a hub, lends indirect support for MTT. Since the PHG includes connections from entorhinal, parahippocampal, and perirhinal cortices, but not the hippocampus proper, the evidence does not directly indicate specific action of the hippocampus but rather the MTL in general. Additionally, processes supporting functional connectivity and recall of distinct types of information were elucidated by the authors. This discovery could lead to clinical interventions targeting specific types of cognitive processes including memory retrieval. As neurosurgery continues to expand toward treating cognitive disorders, a network-level understanding of mechanisms and components of memory systems will prove invaluable.

Imaging of amyloid β in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism

Connectomics Sheds New Light on Alzheimer’s Disease

P2-63. Functional connectivity from the dorso-lateral and medial parts of the parietal lobe: a cortico-cortical evoked potential study

Stuttering is based on a maldevelopment of speech-relevant brain regions and is associated later in life with left perisylvian grey and white matter anomalies and right-hemispheric functional compensation attempt. We hypothesized that in adult stutterers left-hemispheric structural anomalies alter the functional connectivity of the speech production network which prompts stutterers to use right-hemispheric strategies to reduce symptoms. To study anatomical and functional connectivity during overt reading, we performed a structural (DTI) and functional (EPI) study on 13 male adult stutterers and 13 male matched fluent control subjects. Anatomical connectivity was assessed by comparing values of fractional anisotropy using TBSS for FSL and functional connectivity was studied by comparing psychophysiological interactions for overt>covert reading in SPM. Anatomical connectivity changes were restricted to the left hemisphere: We confirmed (Sommer et al., Lancet 2002) an FA reduction below the somatomotor representation of articulation and found pathologically enhanced FA values in fibre tracts below the left inferior frontal gyrus, anterior insula and in the anterior segment of the arcuate fasciculus. The increases and decreases of anatomical connectivity were accompanied by similar changes in functional connectivity of the corresponding brain regions: Functional connectivity during overt>covert reading was reduced between the articulatory motor cortex and the superior temporal gyrus while it was enhanced between the inferior frontal and the supramarginal gyrus compared to fluent controls. We interpret the concordant alterations in functional connectivity in adult stutterers as a consequence of pathological anatomical connectivity on the basis of a left perisylvian maldevelopment in early childhood. Thus, linking comparative analyses of anatomical and functional connectivity helps understanding how structural pathology translates into dysfunction.