This chapter serves as a brief overview in outline form of basic brain neuroscience and pathophysiology with specific relevance to the practice of brain injury medicine. This limited review is intended to help establish a very basic neuroscientific foundation for understanding human functionality and pathophysiological processes through which it may be degraded by brain injury. For further details regarding relevant basic brain neuroscience, the reader is referred to reference textbooks in basic and cognitive neuroscience. Anatomical details and basic functional anatomy of the central nervous system (CNS) are covered in Chapter 1 . In this chapter, the general functional organization of the CNS is discussed followed by a review of basic pathophysiology of traumatic brain injury (TBI). A scheme for the overall organization of various functional brain subsystems is shown in Box 2.1 .
Neuroautonomic visceral subsystems
Visceral sensorimotor subsystems
Visceral efferent (motor) cranial nerve (CN) subsystems
General visceral efferent (GVE) (smooth/cardiac muscle and glands)
- 1.
GVE fibers carry parasympathetic autonomic axons. The following CNs carry general visceral efferent fibers:
- A.
CN III (Edinger-Westphal nucleus): Preganglionic fibers from the Edinger-Westphal nucleus terminate in the ciliary ganglion and the postganglionic fibers innervate the pupil.
- B.
CN VII (superior salivatory nucleus): The preganglionic fibers from the superior salivatory nucleus terminate in the pterygopalatine and submandibular ganglion. The postganglionic fibers innervate the lacrimal gland (from the pterygopalatine ganglion) and the submandibular and sublingual gland (from the submandibular ganglion).
- C.
CN IX (inferior salivatory nucleus): The preganglionic fibers from the inferior salivatory nucleus terminate in the otic ganglion, and the postganglionic fibers innervate the parotid gland.
- D.
CN X (dorsal motor nucleus): The dorsal motor nucleus innervates the abdominal viscera.
- A.
Special visceral efferent (SVE) (to branchial/pharyngeal musculature)
- 2.
CN V (muscles of mastication, first branchial arch)
- 3.
CN VII (muscles of facial expression, second branchial arch)
- 4.
CN IX (stylopharyngeus muscle, third branchial arch)
- 5.
CN X (muscles of the soft palate and pharynx, fourth branchial arch)
- 6.
CN XI (muscles of the larynx/sternocleidomastoid [SCM]/trapezius, sixth branchial arch)
Visceral afferent (sensory) CN subsystems
General visceral afferent (GVA) (from internal organs, vasculature, glands)
- 1.
CNs IX and X
Special visceral afferent (SVA) (from olfactory and taste/gustatory receptors)
- 2.
CNs I (olfactory), VII, IX, and X (gustatory)
Spinal efferent subsystems
Sympathetic spinal efferent subsystem (SympSE)
- 1.
Intermediolateral nucleus of lateral gray column of spinal cord
- 2.
Extends from T1 down to L2 spinal levels
- 3.
Sympathetic ganglionic chain
Parasympathetic spinal efferent subsystem (ParasympSE)
- 4.
Pelvic splanchnic efferents to S2–S4 sacral roots
Central autonomic network (CAN)
- 1.
Anterior cingulate cortex
- 2.
Ventromedial prefrontal cortex
- 3.
Insular cortex
- 4.
Amygdala
- E.
Hypothalamus
- F.
Periaqueductal gray matter
- G.
Parabrachial nucleus of the pons
- H.
Locus coeruleus (norepinephrine)
- I.
Nucleus of the tractus solitarius
- J.
Ventrolateral reticular formation of the medulla
- K.
Medullary raphe nuclei (serotonin)
Special somatic afferent (sensory) subsystems (SSA)
- 1.
Visual
- A.
Visual afferent subsystem
- B.
Visuomotor/oculomotor subsystem
- A.
- 2.
Auditory
- 3.
Vestibular
General somatic efferent (motor) subsystems (GSE)
- 1.
Primary motor cortex
- 2.
Premotor cortical areas
- 3.
Corticobulbar and corticospinal motor tracts
- 4.
GSE cranial motor nuclei
- 5.
Subcortically originating descending spinal motor tracts
- A.
Lateral tracts
Rubrospinal
- B.
Ventromedial tracts
Tectospinal
Vestibulospinal
Pontine (medial) reticulospinal
Medullary (lateral) reticulospinal
- A.
- 6.
Spinal motor neuron nuclei and related segmental subsystem
- 7.
Motor units as basic element of somatomotor function
General somatic afferent (sensory) subsystems (GSA)
- 1.
Primary, secondary, and supplementary somatosensory cortex
- 2.
Sensory relay nuclei of the thalamus
- 3.
GSA cranial sensory nuclei
- 4.
Dorsal column/medial lemniscal subsystem (“epicritic” modalities)
- 5.
Spinothalamic/anterolateral fasciculus subsystem (“protocritic” modalities)
- 6.
Receptors and DRG neurons as basic somatosensory elements
Neuromodulatory subsystems of the reticular activating system ( table 2.1 )
| Neurotransmitter | Receptor | Source Nuclear System(s) | Projection Sites | Presumed Function | Effect on Cognition | Main Behavioral Effects |
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Cerebral premotor associative and attentional cognitive functional networks ( table 2.2 )
| Network Name | Function | Activation | Deactivation | Functional Hubs |
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Cortically reentrant motor efferent modulatory support subsystems
- 1.
Cerebellum
- 2.
Basal ganglia
Greater limbic subsystem
- 1.
Hippocampus
- 2.
Amygdala
- 3.
Hypothalamus
General state controls over functional brain networks
Systematically ordered groups of cell bodies organized into several systems of nuclei are found in the reticular core of the brainstem and midbrain and project widely throughout the CNS, releasing specific neurotransmitters.
Such neurotransmitters—often called neuromodulators—have a modulatory influence over local synaptic transmission across broad swaths of the CNS, including the cerebral cortex, cerebellum, basal ganglia, limbic system nuclei, and spinal cord.
These nuclear systems have been called components of a reticular activating system (RAS) based in gray matter of the reticular core of the brainstem and midbrain regions.
Conceptualize this general structure as a central multifunctional control system that exerts widespread global state parameter influences over the local dynamics of functional brain networks distributed throughout various subsystems of the CNS.
Each separate nuclear system is associated with a specific neurotransmitter.
Targets to which these cells project may have a range of different receptors all responding to the same neurotransmitter. The effect on the target varies depending on which receptor is activated. Four of these key neuromodulatory systems are characterized in Table 2.1 .
Large-scale whole-brain functional neural network dynamics exerting cognitive control —conceived of as the capacity of neural systems to support cognitive operations such as attention, memory, and executive function—can then be studied in terms of the interaction between these central neuromodulatory parametric controls and the local network dynamics of the functional connectome operating in different brain regions. There are a multitude of functional brain networks identifiable throughout the CNS distributed across multiple spatial scales; here we will focus exclusively on the large-scale functional networks involving the cerebral cortex, called intrinsic connectivity networks (ICNs), because these networks are most directly connected to the dynamics of cognitive control. Traumatic axonal injury (TAI) involving cerebral white matter significantly disrupts the operation of these networks, manifesting in disorders of cognitive control. The brain is a dynamic system transitioning between different momentary mind/brain states in a microgenetic process through which complex behaviors emerge.
Developing concepts in cognitive control based on studies of resting-state functional magnetic resonance imaging (rs-fMRI) indicate cognition emerges through coordinated interaction between multiple anticorrelated ICNs, including those described in Table 2.2 . ,
Dynamic transitioning between different cortical networks and associated brain states is facilitated through interactions between ICN dynamics and the neuromodulatory systems sending control signals up out of the reticular core of brainstem and midbrain.
Basic neurophysiology of cognitive control
There are two different modes of brain activation corresponding to two different philosophical conceptions of cortical function associated with cognitive control:
- •
The “connectionist theory” of localization of specific functional modules in different specialized cortical regions that become functionally networked and
- •
The “holistic theory” of functional pluripotentiality, which recognizes significant redundancy and functional overlap allowing for substantial neuroplasticity and flexibility.
In the first activation mode, referred to as the high-modularity mode, activation of cerebral cortex occurs in segregated networks with specialized functions. This corresponds to linking up of functional modules into dynamic subsystems generating the coordinated capacity to meet cognitive demands of a task.
In the second activation mode, referred to as the low-modularity or integrative mode, there is a broad diffuse activation of cortical fields without segregation into distinct focal modules.
Recent studies of time-resolved fMRI (tr-fMRI) have demonstrated that although the brain is organized into dynamic functional networks based on correlational analysis of rs-fMRI, rapid fluctuations occur between segregated states of high modularity and integrated states of low modularity. , Dynamic switching between these states is associated with outflow from ascending neuromodulatory systems in the brainstem reticular core. Tractography using diffusion tensor imaging to map cerebral white matter tracts demonstrates dynamic functional connectivity is more closely aligned with structural connectivity during low-modularity integrated cognitive brain states. Complex network theory has been applied to understanding how dynamic functional network connectivity enables the brain to flexibly engage in complex activities. Successful cognitive function is associated with the capacity for dynamic reconfiguration of brain network topologies in response to cognitive demands of a task. , Effects of brain injury can be conceptualized in this context as diminished functional network dynamics. , Impaired dynamics can be tracked longitudinally following brain injury and used to establish connectomic indicators of severity of injury and project recovery.
Characteristics of functional brain network dynamics such as network modularity have significant implications for recovery process and potential impact of rehabilitation interventions.
Pathophysiology of brain injury and recovery in space and time
Brain injury is a highly complex heterogeneous condition involving the most complex organ in the body. Etiologic processes involved in the production of acquired brain injury span every known disease category. We focus here on pathophysiology associated with mechanical trauma and will limit the discussion to a general overview of broad pathophysiological principles without examining details of the pathomechanics or injury classification and assessment (see Chapters 1 and 4 ). Several review articles cover aspects of brain injury pathophysiology in much further detail than can be addressed here. An overview of TBI pathophysiology is provided in Fig. 2.1 .
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