Hippocampal Discoveries: Spatial View Cells, Connectivity, and Computations for Memory and Navigation, in Primates Including Humans.

Two key series of discoveries about the hippocampus are described. One is the discovery of hippocampal spatial view cells in primates. This discovery opens the way to a much better understanding of human episodic memory, for episodic memory prototypically involves a memory of where people or objects or rewards have been seen in locations "out there" which could never be implemented by the place cells that encode the location of a rat or mouse.

Selective Brain Activations and Connectivities Related to the Storage and Recall of Human Object-Location, Reward-Location, and Word-Pair Episodic Memories.

Different cortical systems to the hippocampus were activated using fMRI during different types of episodic memory task. For object with scene location episodic memory, the activations were high in cortical systems involved in spatial processing, including the ventromedial visual and medial parahippocampal system. These activations for the medial parahippocampal system were higher in the right hemisphere.

Hippocampal storage and recall of neocortical "What"-"Where" representations.

A key question for understanding the function of the hippocampus in memory is how information is recalled from the hippocampus to the neocortex. This was investigated in a neuronal network model of the hippocampal system in which "What" and "Where" neuronal firing rate vectors were applied to separate neocortical modules, which then activated entorhinal cortex "What" and "Where" modules, then the dentate gyrus, then CA3, then CA1, then the entorhinal cortex, and then the backprojections to the neocortex. A rate model showed that the whole system could be trained to recall "Where" in the neocortex from "What" applied as a retrieval cue to the neocortex, and could in principle be trained up towards the theoretical capacity determined largely by the number of synapses onto any one neuron divided by the sparseness of the representation.

A ventromedial visual cortical 'Where' stream to the human hippocampus for spatial scenes revealed with magnetoencephalography.

The primate including the human hippocampus implicated in episodic memory and navigation represents a spatial view, very different from the place representations in rodents. To understand this system in humans, and the computations performed, the pathway for this spatial view information to reach the hippocampus was analysed in humans. Whole-brain effective connectivity was measured with magnetoencephalography between 30 visual cortical regions and 150 other cortical regions using the HCP-MMP1 atlas in 21 participants while performing a 0-back scene memory task.

Subthalamic and pallidal oscillations and their couplings reflect dystonia severity and improvements by deep brain stimulation.

Background: Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) and subthalamic nucleus (STN) is employed for the treatment of dystonia. Pallidal low-frequency oscillations have been proposed as a pathophysiological marker for dystonia. However, the role of subthalamic oscillations and STN-GPi coupling in relation to dystonia remains unclear.

The memory systems of the human brain and generative artificial intelligence.

Generative Artificial Intelligence foundation models (for example Generative Pre-trained Transformer - GPT - models) can generate the next token given a sequence of tokens. How can this 'generative AI' be compared with the 'real' intelligence of the human brain, when for example a human generates a whole memory in response to an incomplete retrieval cue, and then generates further prospective thoughts? Here these two types of generative intelligence, artificial in machines and real in the human brain are compared, and it is shown how when whole memories are generated by hippocampal recall in response to an incomplete retrieval cue, what the human brain computes, and how it computes it, are very different from generative AI. Key differences are the use of local associative learning rules in the hippocampal memory system, and of non-local backpropagation of error learning in AI.

Selective activations and functional connectivities to the sight of faces, scenes, body parts and tools in visual and non-visual cortical regions leading to the human hippocampus.

Connectivity maps are now available for the 360 cortical regions in the Human Connectome Project Multimodal Parcellation atlas. Here we add function to these maps by measuring selective fMRI activations and functional connectivity increases to stationary visual stimuli of faces, scenes, body parts and tools from 956 HCP participants. Faces activate regions in the ventrolateral visual cortical stream (FFC), in the superior temporal sulcus (STS) visual stream for face and head motion; and inferior parietal visual (PGi) and somatosensory (PF) regions.

A theory of hippocampal function: New developments.

We develop further here the only quantitative theory of the storage of information in the hippocampal episodic memory system and its recall back to the neocortex. The theory is upgraded to account for a revolution in understanding of spatial representations in the primate, including human, hippocampus, that go beyond the place where the individual is located, to the location being viewed in a scene. This is fundamental to much primate episodic memory and navigation: functions supported in humans by pathways that build 'where' spatial view representations by feature combinations in a ventromedial visual cortical stream, separate from those for 'what' object and face information to the inferior temporal visual cortex, and for reward information from the orbitofrontal cortex.

Two what, two where, visual cortical streams in humans.

ROLLS, E. T. Two What, Two Where, Visual Cortical Streams in Humans.

Roles of the medial and lateral orbitofrontal cortex in major depression and its treatment.

We describe evidence for dissociable roles of the medial and lateral orbitofrontal cortex (OFC) in major depressive disorder (MDD) from structure, functional activation, functional connectivity, metabolism, and neurochemical systems. The reward-related medial orbitofrontal cortex has lower connectivity and less reward sensitivity in MDD associated with anhedonia symptoms; and the non-reward related lateral OFC has higher functional connectivity and more sensitivity to non-reward/aversive stimuli in MDD associated with negative bias symptoms. Importantly, we propose that conventional antidepressants act to normalize the hyperactive lateral (but not medial) OFC to reduce negative bias in MDD; while other treatments are needed to operate on the medial OFC to reduce anhedonia, with emerging evidence suggesting that ketamine may act in this way.

Irritable Bowel Syndrome Is Associated With Brain Health by Neuroimaging, Behavioral, Biochemical, and Genetic Analyses.

Background: Irritable bowel syndrome (IBS) interacts with psychopathology in a complex way; however, little is known about the underlying brain, biochemical, and genetic mechanisms.

Methods: To clarify the phenotypic and genetic associations between IBS and brain health, we performed a comprehensive retrospective cohort study on a large population. Our study included 171,104 participants from the UK Biobank who underwent a thorough assessment of IBS, with the majority also providing neuroimaging, behavioral, biochemical, and genetic information.

The connectivity of the human frontal pole cortex, and a theory of its involvement in exploit versus explore.

The frontal pole is implicated in humans in whether to exploit resources versus explore alternatives. Effective connectivity, functional connectivity, and tractography were measured between six human frontal pole regions and for comparison 13 dorsolateral and dorsal prefrontal cortex regions, and the 360 cortical regions in the Human Connectome Project Multi-modal-parcellation atlas in 171 HCP participants. The frontal pole regions have effective connectivity with Dorsolateral Prefrontal Cortex regions, the Dorsal Prefrontal Cortex, both implicated in working memory; and with the orbitofrontal and anterior cingulate cortex reward/non-reward system.

Different cortical connectivities in human females and males relate to differences in strength and body composition, reward and emotional systems, and memory.

Sex differences in human brain structure and function are important, partly because they are likely to be relevant to the male-female differences in behavior and in mental health. To analyse sex differences in cortical function, functional connectivity was measured in 36,531 participants (53% female) in the UK Biobank (mean age 69) using the Human Connectome Project multimodal parcellation atlas with 360 well-specified cortical regions. Most of the functional connectivities were lower in females (Bonferroni corrected), with the mean Cohen's d =  - 0.

Hierarchical organization of the human ventral visual streams revealed with magnetoencephalography.

The hierarchical organization between 25 ventral stream visual cortical regions and 180 cortical regions was measured with magnetoencephalography using the Human Connectome Project Multimodal Parcellation atlas in 83 Human Connectome Project participants performing a visual memory task. The aim was to reveal the hierarchical organization using a whole-brain model based on generative effective connectivity with this fast neuroimaging method. V1-V4 formed a first group of interconnected regions.

Emotion, motivation, decision-making, the orbitofrontal cortex, anterior cingulate cortex, and the amygdala.

The orbitofrontal cortex and amygdala are involved in emotion and in motivation, but the relationship between these functions performed by these brain structures is not clear. To address this, a unified theory of emotion and motivation is described in which motivational states are states in which instrumental goal-directed actions are performed to obtain rewards or avoid punishers, and emotional states are states that are elicited when the reward or punisher is or is not received. This greatly simplifies our understanding of emotion and motivation, for the same set of genes and associated brain systems can define the primary or unlearned rewards and punishers such as sweet taste or pain.

Hippocampal spatial view cells, place cells, and concept cells: View representations.

A commentary is provided on issues raised in the Special Issue of Hippocampus (2023) on hippocampal system view representations. First, the evidence for hippocampal and parahippocampal spatial view cells in primates including humans shows that the allocentric representations provided by at least some of these cells are very useful for human memory in that where objects and rewards are seen in the world "out there" is a key component of episodic memory and navigation. Spatial view cell representations provide for memory and navigation to be independent of the place where the individual is currently located and of the egocentric coordinates of the viewed location and the facing direction of the individual.

Lifestyle risks associated with brain functional connectivity and structure.

Some lifestyle factors are related to health and brain function and structure, but the brain systems involved are incompletely understood. A general linear model was used to test the associations of the combined and separate lifestyle risk measures of alcohol use, smoking, diet, amounts of physical activity, leisure activity, and mobile phone use, with brain functional connectivity with the high resolution Human Connectome Project (HCP) atlas in 19,415 participants aged 45-78 from the UK Biobank, with replication with HCP data. Higher combined lifestyle risk scores were associated with lower functional connectivity across the whole brain, but especially of three brain systems.

A Phenome-wide Association and Mendelian Randomization Study for Alzheimer's Disease: A Prospective Cohort Study of 502,493 Participants From the UK Biobank.

Background: Considerable uncertainty remains regarding associations of multiple risk factors with Alzheimer's disease (AD). We aimed to systematically screen and validate a wide range of potential risk factors for AD.

Methods: Among 502,493 participants from the UK Biobank, baseline data were extracted for 4171 factors spanning 10 different categories.

Intersecting distributed networks support convergent linguistic functioning across different languages in bilinguals.

How bilingual brains accomplish the processing of more than one language has been widely investigated by neuroimaging studies. The assimilation-accommodation hypothesis holds that both the same brain neural networks supporting the native language and additional new neural networks are utilized to implement second language processing. However, whether and how this hypothesis applies at the finer-grained levels of both brain anatomical organization and linguistic functions remains unknown.

Odor encoding by signals in the olfactory bulb.

To understand the operation of the olfactory system, it is essential to know how information is encoded in the olfactory bulb. We applied Shannon information theoretic methods to address this, with signals from up to 57 glomeruli simultaneously optically imaged from presynaptic inputs in glomeruli in the mouse dorsal (dOB) and lateral (lOB) olfactory bulb, in response to six exemplar pure chemical odors. We discovered that, first, the tuning of these signals from glomeruli to a set of odors is remarkably broad, with a mean sparseness of 0.

Auditory cortical connectivity in humans.

To understand auditory cortical processing, the effective connectivity between 15 auditory cortical regions and 360 cortical regions was measured in 171 Human Connectome Project participants, and complemented with functional connectivity and diffusion tractography. 1. A hierarchy of auditory cortical processing was identified from Core regions (including A1) to Belt regions LBelt, MBelt, and 52; then to PBelt; and then to HCP A4.