Disconnection of alpha oscillations within default mode network associated with memory dysfunction in amnestic MCI.

OBJECTIVE: Episodic memory dysfunction and alterations of functional connectivity (FC) in default mode network (DMN) were found in patients with amnestic mild cognitive impairment (aMCI). However, previous studies were limited in probing certain oscillations within the DMN. This study employed measures of resting-state FC across various oscillations within the DMN to comprehensively examine the FC and its association with episodic memory performance in aMCI. METHODS: Twenty-six healthy controls (HC) and 30 patients with aMCI were recruited to perform resting-state magnetoencephalographic recordings. We compared the spectral powers and peak frequency values in each frequency band and FC within the DMN between these two groups. The associations of FC values with memory performance were also examined. RESULTS: No significant between-group differences in spectral powers and peak frequency values were observed in the regional nodes. Patients with aMCI exhibited diminished alpha-band FC as compared to HC. Furthermore, lower alpha-band FC between the medial temporal cortex - and the posterior cingulate cortex/precuneus was correlated with poorer memory performance. CONCLUSIONS: Aberrant DMN connectivity, particularly in the alpha frequency range, might be a neural correlate of episodic memory impairment. SIGNIFICANCE: Our results inform the potential development of brain stimulation in managing memory impairments in aMCI.

Early memory deficits and extensive brain network disorganization in the AppNL-F/MAPT double knock-in mouse model of familial Alzheimer's disease.

A critical challenge in current research on Alzheimer's disease (AD) is to clarify the relationship between network dysfunction and the emergence of subtle memory deficits in itspreclinical stage. The AppNL-F/MAPT double knock-in (dKI) model with humanized ß-amyloid peptide (Aß) and tau was used to investigate both memory and network dysfunctions at an early stage. Young male dKI mice (2 to 6 months) were tested in three tasks taxing different aspects of recognition memory affected in preclinical AD. An early deficit first appeared in the object-place association task at the age of 4 months, when increased levels of ß-CTF and Aß were detected in both the hippocampus and the medial temporal cortex, and tau pathology was found only in the medial temporal cortex. Object-place task-dependent c-Fos activation was then analyzed in 22 subregions across the medial prefrontal cortex, claustrum, retrosplenial cortex, and medial temporal lobe. Increased c-Fos activation was detected in the entorhinal cortex and the claustrum of dKI mice. During recall, network efficiency was reduced across cingulate regions with a major disruption of information flow through the retrosplenial cortex. Our findings suggest that early perirhinal-entorhinal pathology is associated with abnormal activity which may spread to downstream regions such as the claustrum, the medial prefrontal cortex and ultimately the key retrosplenial hub which relays information from frontal to temporal lobes. The similarity between our findings and those reported in preclinical stages of AD suggests that the AppNL-F/MAPT dKI model has a high potential for providing key insights into preclinical AD.

Correlations Between the Microstructural Changes of the Medial Temporal Cortex and Mild Cognitive Impairment in Patients With Cerebral Small Vascular Disease (cSVD): A Diffusion Kurtosis Imaging Study.

Object: The purpose of our study was to investigate the microstructural changes of the medial temporal cortex in mild cognitive impairment (MCI) patients with cerebral small vascular disease (cSVD) using diffusion kurtosis imaging (DKI) and to examine whether DKI parameters are correlated with MCI. Method: A total of 82 cSVD patients admitted to the Department of Neurology Beijing Chaoyang Hospital, Capital Medical University, were retrospectively enrolled in this study. The Montreal cognitive assessment scale (MoCA) score was used to assess overall cognitive function. According to the presence or absence of MCI, these patients were divided into an MCI group (n = 48) and a non-MCI group (n = 34). The general clinical data of the two groups were collected and analyzed. The regions of interest (ROIs) in the medial temporal cortex were selected for investigation. The averaged values of DKI parameters were measured in each ROI and compared between the two groups, and the correlations between DKI parameters and MoCA score and between diffusion and kurtosis parameters were examined. Results: Compared to the non-MCI group, MCI patients showed significantly increased mean diffusion (MD) and radial diffusion (RD) and significantly decreased mean kurtosis (MK) in the left hippocampus (P = 0.005, 0.006, 0.002, respectively). In the left hippocampus, fractional anisotropy (FA), MK, radial kurtosis (RK), and kurtosis fractional anisotropy (KFA) showed significantly positive correlations with MoCA score (r = 0.374, 0.37, 0.392, 0.242, respectively, all P < 0.05), while MK and RD were negatively correlated with MoCA score (r = -0.227, -0.255, respectively, both P < 0.05). In the left parahippocampal region, axial kurtosis (AK) and KFA were positively correlated with MoCA score (r = 0.228, 0.282, respectively, both P < 0.05), while RK was positively correlated with MoCA score in the right parahippocampal region (r = 0.231, P < 0.05). Significant correlations of MD with MK, RD with RK, and FA with KFA were observed in the medial temporal cortex (r = -0.254, -0.395, 0.807, respectively, all P < 0.05) but not of axial diffusion (AD) with AK. Conclusion: The DKI technique can be used to observe microstructural changes of the medial temporal cortex in MCI patients with cSVD. The DKI-derived parameters might be a feasible means of evaluating patients with MCI.

Recognition Memory Dysfunction Relates to Hippocampal Subfield Volume: A Study of Cognitively Normal and Mildly Impaired Older Adults.

OBJECTIVES: The current study examined recognition memory dysfunction and its neuroanatomical substrates in cognitively normal older adults and those diagnosed with mild cognitive impairment (MCI). METHODS: Participants completed the Mnemonic Similarity Task, which provides simultaneous measures of recognition memory and mnemonic discrimination. They also underwent structural neuroimaging to assess volume of medial temporal cortex and hippocampal subfields. RESULTS: As expected, individuals diagnosed with MCI had significantly worse recognition memory performance and reduced volume across medial temporal cortex and hippocampal subfields relative to cognitively normal older adults. After controlling for diagnostic group differences, however, recognition memory was significantly related to whole hippocampus volume, and to volume of the dentate gyrus/CA3 subfield in particular. Recognition memory was also related to mnemonic discrimination, a fundamental component of episodic memory that has previously been linked to dentate gyrus/CA3 structure and function. DISCUSSION: Results reveal that hippocampal subfield volume is sensitive to individual differences in recognition memory in older adults independent of clinical diagnosis. This supports the notion that episodic memory declines along a continuum within this age group, not just between diagnostic groups.

Anatomical pathways for auditory memory II: information from rostral superior temporal gyrus to dorsolateral temporal pole and medial temporal cortex.

Auditory recognition memory in non-human primates differs from recognition memory in other sensory systems. Monkeys learn the rule for visual and tactile delayed matching-to-sample within a few sessions, and then show one-trial recognition memory lasting 10-20 min. In contrast, monkeys require hundreds of sessions to master the rule for auditory recognition, and then show retention lasting no longer than 30-40 s. Moreover, unlike the severe effects of rhinal lesions on visual memory, such lesions have no effect on the monkeys' auditory memory performance. The anatomical pathways for auditory memory may differ from those in vision. Long-term visual recognition memory requires anatomical connections from the visual association area TE with areas 35 and 36 of the perirhinal cortex (PRC). We examined whether there is a similar anatomical route for auditory processing, or that poor auditory recognition memory may reflect the lack of such a pathway. Our hypothesis is that an auditory pathway for recognition memory originates in the higher order processing areas of the rostral superior temporal gyrus (rSTG), and then connects via the dorsolateral temporal pole to access the rhinal cortex of the medial temporal lobe. To test this, we placed retrograde (3% FB and 2% DY) and anterograde (10% BDA 10,000 mW) tracer injections in rSTG and the dorsolateral area 38 DL of the temporal pole. Results showed that area 38DL receives dense projections from auditory association areas Ts1, TAa, TPO of the rSTG, from the rostral parabelt and, to a lesser extent, from areas Ts2-3 and PGa. In turn, area 38DL projects densely to area 35 of PRC, entorhinal cortex (EC), and to areas TH/TF of the posterior parahippocampal cortex. Significantly, this projection avoids most of area 36r/c of PRC. This anatomical arrangement may contribute to our understanding of the poor auditory memory of rhesus monkeys.

Neurophysiological traces of the reader's geographical perspective associated with the deictic verbs of motion to go and to come.

This ERP study explores how participants activate their own geographical perspective, while reading sentences describing a motion (to come or to go), or a static spatial relation (to be) referred either to the participant's current location or a distant place. The ERPs recorded at the place names revealed that, compared to "distant places", "close places" enhanced ERP's components, associated with motivational relevance, in the context of the deictic verbs of motion to come and to go, but not in the context of the static verb to be. Also, in the context of the verbs of motion source estimation showed that "close places" elicited more activity than "distant places" in the medial temporal cortex (around the parahippocampal gyrus), suggesting projection of the reader's self-relevant information, or retrieval of geographical episodic memories. Finally, sentences describing motions congruent with the self-perspective (e.g. "going to distant place") elicited less activation than sentences incongruent with the self-perspective (e.g. "coming to distant place") in the right fronto-polar cortex and in the posterior cingulate cortex, regions generally associated with the other's perspective or with self/other perspective conflict. These findings provide information on the brain processes underlying readers' perspective taking, guided by the deictic verbs of motion.

Proton magnetic resonance spectroscopy (MRS) in on-line game addiction.

Recent brain imaging studies suggested that both the frontal and temporal cortices are important candidate areas for mediating the symptoms of internet addiction. We hypothesized that deficits of prefrontal and temporal cortical function in patients with on-line game addiction (PGA) would be reflected in decreased levels of N-acetyl aspartate (NAA) and cytosolic, choline containing compound (Cho). Seventy three young PGA and 38 age and sex matched healthy control subjects were recruited in the study. Structural MR and (1)H MRS data were acquired using a 3.0 T MRI scanner. Voxels were sequentially placed in right frontal cortex and right medial temporal cortices. In the right frontal cortex, the levels of NAA in PGA were lower than those in healthy controls. In the medial temporal cortex, the levels of Cho in PGA participants were lower than those observed in healthy controls. The Young Internet Addiction Scale (YIAS) scores and perseverative responses in PGA were negatively correlated with the level of NAA in right frontal cortex. The Beck Depressive Inventory (BDI) scores in the PGA cohort were negatively correlated with Cho levels in the right temporal lobe. To the best of our knowledge, this is the first MRS study of individuals with on-line game addiction. Although, the subjects with on-line game addiction in the current study were free from psychiatric co-morbidity, patients with on-line game addiction appear to share characteristics with ADHD and MDD in terms of neurochemical changes in frontal and temporal cortices.

The very same thing: Extending the object token concept to incorporate causal constraints on individual identity.

The contributions of feature recognition, object categorization, and recollection of episodic memories to the re-identification of a perceived object as the very same thing encountered in a previous perceptual episode are well understood in terms of both cognitive-behavioral phenomenology and neurofunctional implementation. Human beings do not, however, rely solely on features and context to re-identify individuals; in the presence of featural change and similarly-featured distractors, people routinely employ causal constraints to establish object identities. Based on available cognitive and neurofunctional data, the standard object-token based model of individual re-identification is extended to incorporate the construction of unobserved and hence fictive causal histories (FCHs) of observed objects by the pre-motor action planning system. It is suggested that functional deficits in the construction of FCHs are associated with clinical outcomes in both autism spectrum disorders and later-stage stage Alzheimer's disease.

Vocalization Induced CFos Expression in Marmoset Cortex.

All non-human primates communicate with conspecifics using vocalizations, a system involving both the production and perception of species-specific vocal signals. Much of the work on the neural basis of primate vocal communication in cortex has focused on the sensory processing of vocalizations, while relatively little data are available for vocal production. Earlier physiological studies in squirrel monkeys had shed doubts on the involvement of primate cortex in vocal behaviors. The aim of the present study was to identify areas of common marmoset (Callithrix jacchus) cortex that are potentially involved in vocal communication. In this study, we quantified cFos expression in three areas of marmoset cortex - frontal, temporal (auditory), and medial temporal - under various vocal conditions. Specifically, we examined cFos expression in these cortical areas during the sensory, motor (vocal production), and sensory-motor components of vocal communication. Our results showed an increase in cFos expression in ventrolateral prefrontal cortex as well as the medial and lateral belt areas of auditory cortex in the vocal perception condition. In contrast, subjects in the vocal production condition resulted in increased cFos expression only in dorsal premotor cortex. During the sensory-motor condition (antiphonal calling), subjects exhibited cFos expression in each of the above areas, as well as increased expression in perirhinal cortex. Overall, these results suggest that various cortical areas outside primary auditory cortex are involved in primate vocal communication. These findings pave the way for further physiological studies of the neural basis of primate vocal communication.

Anatomical pathways for auditory memory in primates.

Episodic memory or the ability to store context-rich information about everyday events depends on the hippocampal formation (entorhinal cortex, subiculum, presubiculum, parasubiculum, hippocampus proper, and dentate gyrus). A substantial amount of behavioral-lesion and anatomical studies have contributed to our understanding of the organization of how visual stimuli are retained in episodic memory. However, whether auditory memory is organized similarly is still unclear. One hypothesis is that, like the "visual ventral stream" for which the connections of the inferior temporal gyrus with the perirhinal cortex are necessary for visual recognition in monkeys, direct connections between the auditory association areas of the superior temporal gyrus and the hippocampal formation and with the parahippocampal region (temporal pole, perhirinal, and posterior parahippocampal cortices) might also underlie recognition memory for sounds. Alternatively, the anatomical organization of memory could be different in audition. This alternative "indirect stream" hypothesis posits that, unlike the visual association cortex, the majority of auditory information makes one or more synapses in intermediate, polymodal areas, where they may integrate information from other sensory modalities, before reaching the medial temporal memory system. This review considers anatomical studies that can support either one or both hypotheses - focusing on anatomical studies on the primate brain, primarily in macaque monkeys, that have reported not only direct auditory association connections with medial temporal areas, but, importantly, also possible indirect pathways for auditory information to reach the medial temporal lobe memory system.