-
Schizophrenia Research Aug 2020Synchronized and coherent activity in resting-networks during normal brain functioning could be altered in disconnection syndrome like schizophrenia. Study of neural...
Synchronized and coherent activity in resting-networks during normal brain functioning could be altered in disconnection syndrome like schizophrenia. Study of neural oscillations as assessed by EEG appears to be a promising proposition to understand the pathophysiology of schizophrenia in patients and their first-degree relatives, where disturbances in neural oscillations point towards genetic predisposition. Therefore, present study aims at establishing EEG based biomarkers for early detection and management strategies. Thirty-two patients with schizophrenia, 28 first-degree relatives and 31 healthy controls (HC) participated in the study. Resting brain activity was recorded using 128-channel electroencephalography. After pre-processing and independent component analysis (ICA), an equivalent current dipole was estimated for each IC. Total of 1551 independent and localizable EEG components across all groups were used in subsequent analysis. Power spectral density and source coherence between IC clusters were computed. Patients and first-degree relatives displayed significantly higher power spectral density (PSD) than HC for all frequency bands in left parahippocampal gyrus (PHG) (-7, -26, 8; BA 27). Another region within left deep PHG (-4, -28, 1), however, distinguished patients from first-degree relatives and HC in terms of significantly lower PSD in higher frequency bands. Functional connectivity (FC) was found to be lower in patients and higher in relatives compared to HC between different resting-state network areas. In patients, connectivity was lower compared to first-degree relatives. Altered activity within left PHG and FC of primarily this with other areas in resting-state network can serve as state and trait markers of schizophrenia.
Topics: Brain Mapping; Electroencephalography; Humans; Magnetic Resonance Imaging; Neural Pathways; Parahippocampal Gyrus; Schizophrenia
PubMed: 32534839
DOI: 10.1016/j.schres.2020.03.066 -
Nature Reviews. Neuroscience Oct 2021Entorhinal cortical grid cells fire in a periodic pattern that tiles space, which is suggestive of a spatial coordinate system. However, irregularities in the grid... (Review)
Review
Entorhinal cortical grid cells fire in a periodic pattern that tiles space, which is suggestive of a spatial coordinate system. However, irregularities in the grid pattern as well as responses of grid cells in contexts other than spatial navigation have presented a challenge to existing models of entorhinal function. In this Perspective, we propose that hippocampal input provides a key informative drive to the grid network in both spatial and non-spatial circumstances, particularly around salient events. We build on previous models in which neural activity propagates through the entorhinal-hippocampal network in time. This temporal contiguity in network activity points to temporal order as a necessary characteristic of representations generated by the hippocampal formation. We advocate that interactions in the entorhinal-hippocampal loop build a topological representation that is rooted in the temporal order of experience. In this way, the structure of grid cell firing supports a learned topology rather than a rigid coordinate frame that is bound to measurements of the physical world.
Topics: Animals; Entorhinal Cortex; Grid Cells; Hippocampus; Humans; Learning; Models, Neurological; Nerve Net; Space Perception
PubMed: 34453151
DOI: 10.1038/s41583-021-00499-9 -
Nature Communications Apr 2022Extensive studies concluded that homophilic interactions between pre- and postsynaptic teneurins, evolutionarily conserved cell-adhesion molecules, encode the...
Extensive studies concluded that homophilic interactions between pre- and postsynaptic teneurins, evolutionarily conserved cell-adhesion molecules, encode the specificity of synaptic connections. However, no direct evidence is available to demonstrate that teneurins are actually required on both pre- and postsynaptic neurons for establishing synaptic connections, nor is it known whether teneurins are localized to synapses. Using super-resolution microscopy, we demonstrate that Teneurin-3 assembles into presynaptic nanoclusters of approximately 80 nm in most excitatory synapses of the hippocampus. Presynaptic deletions of Teneurin-3 and Teneurin-4 in the medial entorhinal cortex revealed that they are required for assembly of entorhinal cortex-CA1, entorhinal cortex-subiculum, and entorhinal cortex-dentate gyrus synapses. Postsynaptic deletions of teneurins in the CA1 region, however, had no effect on synaptic connections from any presynaptic input. Our data suggest that different from the current prevailing view, teneurins promote the establishment of synaptic connections exclusively as presynaptic cell-adhesion molecules, most likely via their nanomolar-affinity binding to postsynaptic latrophilins.
Topics: Entorhinal Cortex; Hippocampus; Ligands; Neurons; Synapses
PubMed: 35484136
DOI: 10.1038/s41467-022-29751-1 -
Neuron Oct 2023The lateral entorhinal cortex (LEC) is a major cortical input area to the hippocampus, and it is crucial for associative object-place-context memories. An unresolved...
The lateral entorhinal cortex (LEC) is a major cortical input area to the hippocampus, and it is crucial for associative object-place-context memories. An unresolved question is whether these associations are performed exclusively in the hippocampus or also upstream of it. Anatomical evidence suggests that the LEC processes both object and spatial information. We describe here a gradient of spatial selectivity along the antero-posterior axis of the LEC. We demonstrate that the LEC generates distinct spatial maps for different contexts that are independent of object coding and vice versa, thus providing evidence for pure spatial and pure object codes upstream of the hippocampus. While space and object coding occur by and large separately in the LEC, we identified neurons that encode for space and objects conjunctively. Together, these findings point to a scenario in which the LEC sustains both distinct space and object coding and associative space-object coding.
Topics: Entorhinal Cortex; Hippocampus; Neurons
PubMed: 37478849
DOI: 10.1016/j.neuron.2023.06.020 -
Hippocampus Jul 2021The hippocampus and parahippocampal region are essential for representing episodic memories involving various spatial locations and objects, and for using those memories... (Review)
Review
The hippocampus and parahippocampal region are essential for representing episodic memories involving various spatial locations and objects, and for using those memories for future adaptive behavior. The "dual-stream model" was initially formulated based on anatomical characteristics of the medial temporal lobe, dividing the parahippocampal region into two streams that separately process and relay spatial and nonspatial information to the hippocampus. Despite its significance, the dual-stream model in its original form cannot explain recent experimental results, and many researchers have recognized the need for a modification of the model. Here, we argue that dividing the parahippocampal region into spatial and nonspatial streams a priori may be too simplistic, particularly in light of ambiguous situations in which a sensory cue alone (e.g., visual scene) may not allow such a definitive categorization. Upon reviewing evidence, including our own, that reveals the importance of goal-directed behavioral responses in determining the relative involvement of the parahippocampal processing streams, we propose the Goal-directed Interaction of Stimulus and Task-demand (GIST) model. In the GIST model, input stimuli such as visual scenes and objects are first processed by both the postrhinal and perirhinal cortices-the postrhinal cortex more heavily involved with visual scenes and perirhinal cortex with objects-with relatively little dependence on behavioral task demand. However, once perceptual ambiguities are resolved and the scenes and objects are identified and recognized, the information is then processed through the medial or lateral entorhinal cortex, depending on whether it is used to fulfill navigational or non-navigational goals, respectively. As complex sensory stimuli are utilized for both navigational and non-navigational purposes in an intermixed fashion in naturalistic settings, the hippocampus may be required to then put together these experiences into a coherent map to allow flexible cognitive operations for adaptive behavior to occur.
Topics: Entorhinal Cortex; Goals; Hippocampus; Neural Pathways; Parahippocampal Gyrus; Perirhinal Cortex; Temporal Lobe
PubMed: 33394547
DOI: 10.1002/hipo.23295 -
Neuron Mar 2023The adult CA1 region of the hippocampus produces coordinated neuronal dynamics with minimal reliance on its extrinsic inputs. By contrast, neonatal CA1 is tightly linked...
The adult CA1 region of the hippocampus produces coordinated neuronal dynamics with minimal reliance on its extrinsic inputs. By contrast, neonatal CA1 is tightly linked to externally generated sensorimotor activity, but the circuit mechanisms underlying early synchronous activity in CA1 remain unclear. Here, using a combination of in vivo and ex vivo circuit mapping, calcium imaging, and electrophysiological recordings in mouse pups, we show that early dynamics in the ventro-intermediate CA1 are under the mixed influence of entorhinal (EC) and thalamic (VMT) inputs. Both VMT and EC can drive internally generated synchronous events ex vivo. However, movement-related population bursts detected in vivo are exclusively driven by the EC. These differential effects on synchrony reflect the different intrahippocampal targets of these inputs. Hence, cortical and subcortical pathways act differently on the neonatal CA1, implying distinct contributions to the development of the hippocampal microcircuit and related cognitive maps.
Topics: Animals; Mice; Hippocampus; Neurons; Thalamus; Entorhinal Cortex; CA1 Region, Hippocampal
PubMed: 36608692
DOI: 10.1016/j.neuron.2022.12.013 -
Advances in Experimental Medicine and... 2022This chapter gives a short overview of computational models dealing with two fundamental building blocks in spatial cognition: grid and place cells, and of the open... (Review)
Review
This chapter gives a short overview of computational models dealing with two fundamental building blocks in spatial cognition: grid and place cells, and of the open issues such models may help address.
Topics: Entorhinal Cortex; Hippocampus; Models, Neurological
PubMed: 35471544
DOI: 10.1007/978-3-030-89439-9_12 -
Brain : a Journal of Neurology May 2023The hippocampal formation has been implicated in the pathophysiology of schizophrenia, with patients showing impairments in spatial and relational cognition, structural...
The hippocampal formation has been implicated in the pathophysiology of schizophrenia, with patients showing impairments in spatial and relational cognition, structural changes in entorhinal cortex and reduced theta coherence with medial prefrontal cortex. Both the entorhinal cortex and medial prefrontal cortex exhibit a 6-fold (or 'hexadirectional') modulation of neural activity during virtual navigation that is indicative of grid cell populations and associated with accurate spatial navigation. Here, we examined whether these grid-like patterns are disrupted in schizophrenia. We asked 17 participants with diagnoses of schizophrenia and 23 controls (matched for age, sex and IQ) to perform a virtual reality spatial navigation task during magnetoencephalography. The control group showed stronger 4-10 Hz theta power during movement onset, as well as hexadirectional modulation of theta band oscillatory activity in the right entorhinal cortex whose directional stability across trials correlated with navigational accuracy. This hexadirectional modulation was absent in schizophrenia patients, with a significant difference between groups. These results suggest that impairments in spatial and relational cognition associated with schizophrenia may arise from disrupted grid firing patterns in entorhinal cortex.
Topics: Humans; Schizophrenia; Theta Rhythm; Entorhinal Cortex; Grid Cells; Hippocampus
PubMed: 36352511
DOI: 10.1093/brain/awac416 -
Human Brain Mapping Apr 2020Natural scenes are inherently structured, with meaningful objects appearing in predictable locations. Human vision is tuned to this structure: When scene structure is...
Natural scenes are inherently structured, with meaningful objects appearing in predictable locations. Human vision is tuned to this structure: When scene structure is purposefully jumbled, perception is strongly impaired. Here, we tested how such perceptual effects are reflected in neural sensitivity to scene structure. During separate fMRI and EEG experiments, participants passively viewed scenes whose spatial structure (i.e., the position of scene parts) and categorical structure (i.e., the content of scene parts) could be intact or jumbled. Using multivariate decoding, we show that spatial (but not categorical) scene structure profoundly impacts on cortical processing: Scene-selective responses in occipital and parahippocampal cortices (fMRI) and after 255 ms (EEG) accurately differentiated between spatially intact and jumbled scenes. Importantly, this differentiation was more pronounced for upright than for inverted scenes, indicating genuine sensitivity to spatial structure rather than sensitivity to low-level attributes. Our findings suggest that visual scene analysis is tightly linked to the spatial structure of our natural environments. This link between cortical processing and scene structure may be crucial for rapidly parsing naturalistic visual inputs.
Topics: Adult; Brain Mapping; Cerebral Cortex; Electroencephalography; Female; Humans; Magnetic Resonance Imaging; Male; Occipital Lobe; Parahippocampal Gyrus; Photic Stimulation; Space Perception; Visual Perception; Young Adult
PubMed: 31758632
DOI: 10.1002/hbm.24875 -
Physiological Reviews Apr 2022The hippocampal formation is critically involved in learning and memory and contains a large proportion of neurons encoding aspects of the organism's spatial... (Review)
Review
The hippocampal formation is critically involved in learning and memory and contains a large proportion of neurons encoding aspects of the organism's spatial surroundings. In the medial entorhinal cortex (MEC), this includes grid cells with their distinctive hexagonal firing fields as well as a host of other functionally defined cell types including head direction cells, speed cells, border cells, and object-vector cells. Such spatial coding emerges from the processing of external inputs by local microcircuits. However, it remains unclear exactly how local microcircuits and their dynamics within the MEC contribute to spatial discharge patterns. In this review we focus on recent investigations of intrinsic MEC connectivity, which have started to describe and quantify both excitatory and inhibitory wiring in the superficial layers of the MEC. Although the picture is far from complete, it appears that these layers contain robust recurrent connectivity that could sustain the attractor dynamics posited to underlie grid pattern formation. These findings pave the way to a deeper understanding of the mechanisms underlying spatial navigation and memory.
Topics: Action Potentials; Animals; Entorhinal Cortex; Hippocampus; Humans; Learning; Neurons; Pyramidal Cells
PubMed: 34254836
DOI: 10.1152/physrev.00042.2020