This chapter concerns neuro-cognitive development, from conception through to childhood. Breastfeeding has been studied extensively using cross-sectional methods, finding cognitive benefits. However, after controlling for confounding variables and with better designs, beneficial effects are at best small. Maternal undernutrition can result in adverse neurodevelopmental outcomes (e.g., enhanced risk of schizophrenia). Undernutrition during infancy and early childhood causes stunting – inadequate growth for age. Stunting is common (around 500 million children worldwide) and is linked to multiple cognitive impairments, imposing lifelong costs on the individual. As stunting involves a complex interaction between nutrition, brain and environment, dietary remediation alone may not be that effective. Maternal overnutrition is also associated with adverse neurodevelopmental outcomes, but here it is unclear if this relates to poor diet quality, maternal body fat or socio-economic factors. Finally, there are a wide range of specific nutritional deficiencies that affect neurocognitive development, many having lifelong impacts (e.g., thiamine, folate iron, iodine).

This chapter examines the impacts of consuming a Western-style diet (WS-diet), rich in saturated fat, sugar and salt. Animal and human data convincingly show that a WS-diet causes hippocampal and prefrontal cortical impairment. Determining which component of a WS-diet is responsible is not currently clear. Several mechanisms may underpin these adverse effects on the brain: (1) reductions in neurotrophic factors; (2) neuroinflammation; (3) oxidative stress; (4) increased stress responsivity; (5) selective vulnerabilities in the hippocampal blood-brain barrier; and (6) changes to gut microbiota. The last one is intriguing as gut microbiota changes may impair the gut endothelial barrier allowing gut material to leak into the bloodstream, subsequently affecting the brain. Eating a WS-diet has also been linked to poorer mental health (anxiety/depression), it may exacerbate multiple sclerosis, and increased risk for Alzheimer’s and Parkinson’s disease. Finally, obesity may be a consequence of these adverse neural changes, leading to appetitive dysregulation and overeating.

This chapter explores the acute effects of food intake. The first part (Section 3.2) deals with whole meals. Having breakfast may have some limited cognitive benefits, but confounds (the link between breakfast and socio-economic status) and absence of a theoretical rationale are problematic. There were few consistent effects linked with other meal-types, except lunch, which is linked to drowsiness. The second part (Sections 3.3–3.4) considers the impact of glucose on the brain and its basis, finding acute administration assists hippocampal-dependent learning and memory and executive function, but with no impact on self-control. Section three examines if dietary manipulation of amino acids can be used to affect specific monoamine neurotransmitter systems, via loading or depletion. Tryptophan (serotonin precursor) is best studied, with loading generating fatigue and depletion lowering mood in at-risk individuals. Tyrosine (dopamine precursor) loading has facilitative effects on working memory, but the depletion findings are ambiguous. There is little data on histidine (histamine precursor).

This chapter’s purpose is to present the aim of the book, its rationale, focus, approach and the basic concepts necessary to make sense of what follows. The first part outlines the aim and approach, focussing on the impact of diet on the human brain and mind, alongside an outline of the content. The second part provides an overview of the core knowledge and methods that underpin research into diet, brain and mind. This starts with basic nutritional (energy needs, macronutrients, micronutrients) and physiological concepts (metabolism, digestion, regulation). It then covers the key issue of dietary measurement (self-report, observation, biomarkers, manipulation) and its limitations (accuracy, demand, stability over days and decades). The latter part examines the measurement of mind and brain – and its limitations – concentrating, respectively, on neuropsychological tests and imaging approaches. The final part describes our study inclusion criteria, and our rationale for favouring those with a whole diet focus.

This chapter examines the implications arising from the book’s content, and draws some general conclusions. Section 10.2 considers implications on a chapter-by-chapter basis, covering the small effect of breastfeeding on cognition, the nature of energy metabolism in the brain, dietary components versus patterns, the gut–brain axis, caffeine and sugar, immorality and hunger, lifespan extension and depression as a common consequence of nutritional deficiency. Section 10.3 presents conclusions and future directions, organised under three headings. First, the necessity to improve dietary recording methods, examining biomarkers for individual foods, active and passive food image collection, and monitoring eating. Second, nutraceutical and nutrigenomics, with the former’s failure so far to deliver concrete benefits – and why – and the latter’s potential to explain this through understanding individual differences. Third, the translation and reproducibility crises in biomedicine, and some consideration of their solutions as they apply here.

This chapter – focussing on adults – concerns the effects on brain and behaviour of deficiencies in vitamins, minerals and macronutrients, which cannot be synthesised in the body. Section 9.2 examines the neurobehavioural consequences of hypovitaminosis (intake below that recommended) and deficiency for each vitamin, including thiamine (Wernicke’s encephalopathy and Korsakoff’s syndrome), NAD (pellagra) and folate (depression). Section 9.3 covers mineral deficiencies, with notable impacts from iodine (hippocampal impairment and links to neurodegeneration in later life), selenium (hippocampal impairment) and zinc (depression). Section 9.4 examines the two essential macronutrient deficiencies. One covers omega-3 and omega-6 fatty acids, with deficiency linked to depression and neurodegeneration. The other covers the essential amino acids and the brain’s unique deficiency detection mechanism. Depression seems to be a common consequence of deficiency, and deficiency in mid-to-later life seems to link to neurodegeneration, but supplementation generally of individual micronutrients has not revealed much benefit in this regard.

The lampreys (Cyclostomes) represent the oldest group of now-living vertebrates that diverged from the vertebrate evolutionary line leading to mammals 560 million years ago. It is therefore of particular interest to consider if there is a thalamus similar to that of other vertebrates and examine how it is organised. The lamprey thalamus relays both visual and somatosensory information to the cortex (also called the pallium). In addition, the thalamus receives input from both the optic tectum (superior colliculus) and pretectum, as in other vertebrates, and there is, furthermore, a thalamic projection to the striatum from cells located in the periventricular area of the thalamus. Essentially, the basic compartments of the mammalian thalamus are thus represented in the lamprey but with a much smaller number of neurons. The implication is that the essential features of the thalamus had already evolved at the point when the cyclostome lineage diverged from that leading to other vertebrates. We review here what is known regarding the lamprey thalamus from the perspective of anatomy, transmitters, and neurophysiology and also how it compares to mammals, as well as other groups of vertebrates.

The medial geniculate body (MGB) of the thalamus plays a critical role in transforming the dense, high-fidelity auditory coding of the brainstem and midbrain to the sparse, abstract coding used throughout the forebrain to represent the perceptual qualities and behavioral meaning of sound. Here, we review the current state of knowledge on the connectivity, functional processing, and plasticity of interconnected neural circuits linking the MGB and the auditory cortex (ACtx). We describe new findings on the activation of corticothalamic neurons prior to expected sounds and specializations for encoding sound features that unfold on slow timescales that first emerge at the level of the MGB and ACtx. We review the literature on the development and plasticity of the MGB and ACtx, with a particular emphasis on how early auditory experience and adult learning modify sound processing at the level of thalamocortical synapses, circuits, and integrated neural systems. Despite its critical role as the root of forebrain sound processing, direct recordings from anatomically or genetically identified MGB cell types are rarely performed. We conclude by identifying several important knowns and unknowns about the distinct patterns of connectivity and functional specializations of the ventral, dorsal, and medial subdivisions of the MGB that await future investigation.

The motor thalamus is interconnected with the brainstem, cortex, and basal ganglia and plays major roles in planning, sequencing, and executing action. In this chapter, I highlight roles of input-defined thalamic circuits in motor sequence production and learning. Brainstem–motor thalamic pathways carry efference copy signals important for the production of both innate and learned motor sequences, for example, during saccades, grooming, and birdsong. Basal ganglia thalamocortical loops implement aspects of reinforcement learning, including the generation of motor exploration during vocal babbling. Classic "gating" models of basal ganglia–thalamic transmission fail to explain thalamic discharge during behavior, which instead appears strongly driven by cortical inputs. A challenge going forward is to determine if there are conserved principles of thalamic function across diverse motor thalamic subregions.

The thalamocortical system underlies sensory perception, brain-state regulation, movement execution, and cognition. The thalamus and cortex are generated from separate sectors of the embryonic forebrain, and their reciprocal axonal projections have to grow across a complex cellular terrain through it to innervate each other. The corticofugal and thalamocortical projections start to develop synchronously at very early stages when the distances are minimal. The initial topographical organization of these axons is guided by diencephalic and telencephalic molecular gradients. Transient axonal bundles and streams of migrating cell populations then act as a guiding scaffold for these projections. Once they reach their target, the thalamocortical fibers rearrange within the transient subplate zone and later innervate the cortical plate, whereas the corticofugal axons originate from layer 5, layer 6, and subplate/layer 6b neurons and follow a specific developmental sequence as they approach the thalamus, where some of them accumulate before they enter the first -and higher-order thalamic nuclei according to their subtypes and laminar origin. Both thalamocortical and corticothalamic projections are plastic and can reshape after alterations in sensory input or various lesions. Understanding the mechanisms underlying their development and remodeling is vital to comprehending the establishment and plasticity of cortical representations.

Cognitive control refers to our ability to regulate thoughts and actions for adaptive, goal-directed behaviors. Traditionally, cognitive control is thought to be mediated by the prefrontal cortex; however, the thalamus likely plays an important yet underappreciated role. This chapter reviews the role of the human thalamus in cognitive control. We first review anatomical, human functional neuroimaging, and human neuropsychology findings that have investigated the role of the human thalamus in two cognitive control functions: working memory and top-down biasing. To understand how the human thalamus mechanistically supports cognitive control, we then summarize operational principles of thalamocortical circuits from anatomical and neurophysiological studies. Finally, we present an overarching conceptual framework to describe how thalamocortical circuits implement different components of information processing necessary for cognitive control. In conclusion, we refute the traditional view that the thalamus passively relays signals to the cortex for purposeful processing. Instead, emerging evidence suggests that the thalamus actively modulates cortical activity and cortical network interactions to shape and coordinate information processes underlying cognitive control.

The architecture of the thalamus and its reciprocal connections with multiple cortical and subcortical structures are essential to the generation of the thalamo-cortical network oscillations associated with attention, sleep, and consciousness. This chapter provides an overview of the cellular mechanisms underlying thalamo-cortical network oscillations occurring during sleep and their contribution to the architecture of the sleep–wake cycle, including the onset and stability of non–rapid eye movement (NREM) and rapid eye movement (REM) sleep. It further summarizes the influence of the brainstem neuromodulatory system on thalamo-cortical network activity during wakefulness and sleep. Finally, the association between these mechanisms and synaptic plasticity in thalamo-cortical networks is described in the context of sleep-dependent consolidation, or weakening, of previously acquired information in health and disease.

The three anterior thalamic nuclei and the nucleus reuniens are essential for spatial navigation, yet their exact role in this function remains elusive. Specifically, it remains to be answered whether the thalamus acts a simple relay of spatial and executive signals or whether it critically operates on its inputs to convey processed signals to its cortical targets. The anterior thalamus and nucleus reuniens are at the center stage of anatomical networks that share one common aspect: their association with the hippocampus. Here, I review the large body of literature, starting from the classic Papez circuits, which describe how these thalamic nuclei are interconnected with subcortical, medial cortex, and parahippocampal regions, as well as their neuromodulatory inputs. I then provide an overview of the spatial and other electrophysiological correlates of anterior thalamic and reuniens neurons and of how their firing and oscillatory properties depend on ongoing behavior. Finally, I discuss the clinical and experimental evidence pointing to the role of the thalamus in navigation and, specifically, how spatial and executive signals are processed in thalamocortical loops. I conclude by discussing how the same thalamic circuits may be at play in the processing of episodic memories during sleep.

The thalamus traditionally is divided into the dorsal and ventral divisions, with both divisions divided into groups of nuclei. More recent approaches have defined divisions based on functional features, development, and/or evolutionary relationships. The thalamic nuclei are inextricably related to the corresponding divisions of the telencephalon, which is now recognized to have four developmental pallial sectors (the medial sector–derived hippocampal cortices; dorsal sector–derived neocortex; and lateral and ventral sector–derived claustrum, pallial amygdala, and related lateral nuclei in mammals) and the subpallium (which includes the septal nuclei, subpallial amygdala, and basal ganglia in mammals). The two evolutionary divisions of the dorsal thalamus, present in all jawed vertebrates, are the lemnothalamus and collothalamus. In amniotes, elaboration of different pallial sectors and their related dorsal thalamic nuclei was divergent, with the lemnothalamic-related, allocentric spatial mapping abilities selected for early in the line to mammals and the collothalamic-related, egocentric spatial mapping abilities selected for early in the line to reptiles, including birds. Secondarily, the collothalamic system was elaborated in mammals (e.g., LP/pulvinar in primates) and the lemnothalamic system in reptiles (e.g., primary visual and somatosensory nuclei in birds). Commonalities of thalamotelencephalic circuit motifs evolved in both lineages, supporting the functions of complex cognition and consciousness.