Developmental Disorders of the Brain

Nicole J. Rinehart, John L. Bradshaw, Peter G. Enticott

• Publisher: Psychology Press
• Year: 2016
• ISBN:
  9781317432654
• Edition: 2
• Topic: Psychology
• Subtopic: History & Theory in Psychology
• Index: Psychology

Developmental Disorders of the Brain: Brain and Behaviour addresses disabilities that occur or have their roots in the early, developmental phase of life which are of utmost concern to parents, siblings, carers and teachers.

This text describes the latest clinical and behavioral findings of disorders which largely or entirely involve the frontostriatal (basal ganglia) system including Tourette's, Obsessive-Compulsive and Attention-Deficit-Hyperactivity disorders, Schizophrenia, Autism, gambling and addiction, depression, and Conduct, Developmental Motor Co-ordination, and language disorders. Examples of disorders involving the frontocerebellar are also described such as Asperger's disorder, Williams, Fragile X, and Cerebellar Cognitive Affective syndromes, and Friedreich Ataxia. This book also discusses the relevant anatomy, physiology and pathology, and some of the major functions mediated by affected or relevant structures, together with accounts of the latest recording, brain imaging and stimulating techniques related to these kinds of disorders.

Covering both frontostriatal and frontocerebellar, systems which control and direct normal behavior, and which can fail with often distressing consequences during development, as well as addressing behavioural, clinical, pathophysiological and technical aspects, this text is vital to understanding, diagnosis and management of developmental disorders of the brain. This text will be of great interest to clinicians, researchers, teachers and parents.

1 The Basal Ganglia

Katherine Johnson

DOI: 10.4324/9781315692289-1

Introduction

The basal ganglia (BG) are a complex set of subcortical nuclei, consisting of the striatum (the caudate nucleus and the putamen), the globus pallidus, the substantia nigra, and the subthalamic nucleus (Redgrave et al., 2010). They are connected with the cerebral cortex in a series of parallel, largely segregated loops that convey limbic (motivation, emotion), associative (cognitive), and sensorimotor information in a topographically organized manner (Draganski et al., 2008; Karachi et al., 2005; Kemp & Powell, 1970; Lambert et al., 2012; Parent & Hazrati, 1995; Postuma & Dagher, 2006; Redgrave et al., 2010). Functional neuroimaging and connectivity studies have provided validation of these circuits in humans, which correspond with evidence from non-human primate lesion and tracing studies (Stoessl, Lehéricy, & Strafella, 2014). Because they receive connections from all areas of the cortex (Kemp & Powell, 1970), and they project back to the motor output regions of the brain, the BG have been proposed to act as a selector of the most appropriate behaviour for a given situation, based on sensory, limbic, and cognitive information (Redgrave et al., 2010). The exact roles of the BG, however, are still under debate.

The BG are “archaic” in evolutionary terms (Redgrave, Prescott, & Gurney, 1999). All jawed vertebrates have an input station (the striatum) and an output station (the pallidum) (Medina, Abellán, Vicario, & Desfilis, 2014). In tetrapods (four-limbed vertebrates), the dorsal BG are associated with somatosensory behaviour, whilst the ventral BG are associated with motivation (Medina et al., 2014). Given the phylogenetic continuity of the BG, much anatomical and physiology research has been conducted on primates and mammals, with magnetic resonance imaging opening the research field for understanding the anatomy and physiology of the BG in humans. Our understanding of how the BG nuclei connect with the rest of the brain has changed considerably over the past 50 years, with advances in research technologies.

This chapter will review the anatomy, connectivity, and the biochemistry of the BG. It will present some of the models of the way the BG connect with the rest of the brain and how the BG nuclei function together. Some of the proposed roles of the BG will be reviewed.

The anatomy of the basal ganglia

The basal ganglia are a set of interconnected nuclei located in the base of the forebrain (Albin, Young, & Penney, 1989). They consist of the ventral striatum (nucleus accumbens and the olfactory tubercle), the dorsal striatum (the caudate nucleus and putamen), the globus pallidus – both the internal (GPi) and external (GPe) sections, the substantia nigra pars compacta (SNc) and the substantia nigra pars reticulata (SNr), and the subthalamic nucleus (STN).

Inputs into the BG

The striatum receives most of the projections from outside of the BG – but not all. The STN receives direct excitatory afferents from the motor and premotor cortices (Albin et al., 1989), and internally from the GPe, whilst the GPi receives excitatory inputs from the thalamus and the pedunculopontine tegmental nucleus (Nelson & Kreitzer, 2014).

The dorsal striatum (caudate nucleus and putamen) receives glutamatergic topographic projections from the entire neocortex (Kemp & Powell, 1970) and from the thalamus (Smith, Raju, Pare, & Sidibe, 2004). It also receives dopaminergic projections from the ventral tegmental area (VTA) and the SNc, and serotonergic and noradrenergic inputs from the raphe and locus coeruleus (Fujiyama, Takahashi, & Karube, 2015). The ventral striatum receives projections from the hippocampal formation, entorhinal cortex, the olfactory cortex, the anterior cingulate, prelimbic and infralimbic cortices, lateral propisocortical areas, the amygdala, the thalamus (Nakano, 2000) and dopaminergic projections from the VTA and SNc (Björklund & Dunnett, 2007).

Outputs from the BG and thalamus

To date, there are three output regions of the BG – the GPi and the SNr complex, the SNc and VTA, and a recently described third output – a direct γ-Aminobutyric acid (GABA)-ergic projection from the GPe to the frontal cortex (Saunders et al., 2015). The GPi and SNr can be considered as parts of a single neuronal system separated by a white matter tract (Albin et al., 1989). This complex sends inhibitory projections to the thalamus and the midbrain tegmentum (Albin et al., 1989). The GPi also projects to the lateral habenula (cells around the pineal gland), whilst the SNr also projects to the superior colliculus (Albin et al., 1989), which is important for eye movements and orienting behaviour (Nelson & Kreitzer, 2014). The GPi and SNr also outputs to the pedunculopontine tegmental nucleus in the brain stem, which is thought to modulate both motor and attention control (Benarroch, 2013).

The SNc and VTA send dopaminergic projections to many brain regions, with prominent projections to the frontal cortex, limbic areas, and within the BG itself (Björklund & Dunnett, 2007). These dopamine projections form three anatomically and functionally discrete paths – the mesostriatal, mesolimbic, and mesocortical paths, but their origins within the SNc and VTA are intermixed (Björklund & Dunnett, 2007).

The newly described direct projection from the GPe to the frontal cortex releases the inhibitory neurotransmitter GABA and to a lesser degree acetylcholine. This projection in turn is inhibited by the striatal projection neurons of the direct and indirect pathways within the dorsal striatum (see below for more details about the direct and indirect pathways), suggesting it is under the control of the striatum (Saunders et al., 2015). The indirect striatal projection that inhibits the GPe projection to the frontal cortex is sensitive to dopamine 2 receptor signaling (Saunders et al., 2015).

The thalamus projects to the prefrontal cortex, with dense projections to the supplementary motor area (Schell & Strick, 1984) and it also projects back to the dorsal striatum (Smith et al., 2014). The center median/parafascicular complex is the main source of connections between the thalamus and the striatum (Smith et al., 2014). About 50% of its neurons are sent to the dorsal striatum, about one third are sents to the primary motor cortex, and the remaining neurons project to both targets. These projections are topographically organized (Smith et al., 2014). The center median/parafascicular complex is activated during the processing of attention-related stimuli. These thalamic inputs may act to gate corticostriatal transmission by regulating striatal cholinergic interneurons – researchers speculate that this may modulate behavioural switching and set-shifting (Kimura, Minamimoto, Matsumoto, & Hori, 2004; Smith et al., 2014). The intralaminar nuclei of the thalamus receive massive ascending projections from reticular formation of the brain stem, and are part of the reticular activating system that regulates arousal and attention (Smith et al., 2014). The outputs of the BG and thalamus remain topographically organized as part of the limbic, associative, and sensorimotor loops (Berendse & Groenewegen, 1990; Redgrave et al., 2010).

Connections within the BG

Within the BG, there are medium spiny GABAergic neuronal connections between the dorsal striatum and the GPi and SNr (“direct pathway”). There is a connection between the dorsal striatum and the GPe, which then projects to the STN (Albin et al., 1989), and the STN sends projections to the GPi and SNr (“indirect pathway”). The STN also projects back to the GPe (Albin et al., 1989) and the dorsal striatum (Kita & Kitai, 1987). The striatum and the SNc project to each other (Albin et al., 1989). There is also a “hyperdirect pathway” between the cortex, the STN and the GPi, and SNr (Nambu, Tokuno, & Takada, 2002). The GPe neurons send projections to almost every BG nucleus (Nelson & Kreitzer, 2014).

The SNc sends dopaminergic projections to the dorsal and ventral striatum, both the GPi and GPe to the STN, and within the SNc itself (Björklund & Dunnett, 2007). These midbrain dopaminergic neurons can regulate the activity of the dopaminergic neurons themselves and also the release of GABA within the SNr, regulating the activity of its efferent projections (Björklund & Dunnett, 2007).

Dopamine functioning within the BG

The dopaminergic afferents from the SNc modulate the excitatory inputs from the cerebral cortex on the dorsal striatum (Smith et al., 2014). This occurs through a wide variety of pre- and/or post-synaptic mechanisms, depending on the type and the location of the dopamine receptors (Smith et al., 2014). There are two forms of dopamine receptors – the D1 and D2 receptor subtypes. Tonic levels of extracellular dopamine can activate the D2-type receptors (D2, D3, and D4), whilst phasic release of dopamine activates the D1-type receptors (D1, D5) (Da Cunha et al., 2015). All five DA receptors are expressed in the striatum, where D1 and D2 are particularly abundant (Da Cunha et al., 2015). The medium spiny neurons of the striatum predominantly express D1 receptors in the direct, and D2 receptors in the indirect pathways (Da Cunha et al., 2015). D2-like receptors (D2, D3, and D4) are also expressed in the presynaptic terminals of the SNc and VTA dopaminergic neurons and in the terminals of corticostriatal neurons (Da Cunha et al., 2015).

The medium spiny neurons of the dorsal striatum fire only when they are in an “up-state”, where their membrane potentials are closer to the depolarization threshold. They phasically release dopamine in amounts that stimulate the D1-like receptors (D1, D5), which is likely to stimulate firing of neurons in the direct pathway (Da Cunha et al., 2015).

Models of how the BG connect with the rest of the brain

The BG receives projections from all over the cortex and relays projections back again. The functional roles of these projections are open to interpretation and modeling. Over time, scientists have forwarded models of BG functioning, and these have changed with improved understanding of the complexity of this system based on animal research, and with the addition of human data from functional and anatomical magnetic resonance imaging. A historical review of the models of how the BG connects with the rest of the brain is presented here below.

Anatomical and physiological research supports the contention that the BG are part of a series of separate but parallel circuits that funnel projections from broad sections of the cortex into discrete sections of th...

Table of contents

• Cover Page
• Half Title Page
• Series Page
• Title Page
• Copyright Page
• Contents
• List of affiliations
• Acknowledgements
• Preface
• Foreword
• 1 The Basal Ganglia
• 2 The Frontal Cortex
• 3 Cerebellar cognitive affective syndrome
• 4 New Technologies in Clinical Neuroscience
• 5 Developmental Coordination Disorder
• 6 Language Disorder
• 7 Autism Spectrum Disorder
• 8 Attention Deficit Hyperactivity Disorder
• 9 Conduct Disorder and Oppositional Defiant Disorder
• 10 Depression
• 11 Obsessive Compulsive Disorder
• 12 Gilles de la Tourette Syndrome
• 13 Addiction
• 14 Gambling Disorder
• 15 Schizophrenia
• 16 Williams Syndrome
• 17 Friedreich Ataxia
• 18 Fragile X Syndrome and other FMR1-related conditions
• 19 Cerebellar-Frontal-Parietal Axis in Developmental Disorders
• 20 Last Thoughts
• A Postscript
• Index