Answers – 86 References – 87
3.1 Background
3.1.3 Age-Related Changes in Brain Structure and Brain Networks
With aging, several changes are expected in brain structure and function. In general, brain volume declines with age at a rate estimated at 0.5–1% per year. There is evidence on
shrinkage of brain matter and enlargement of ventricles, but this pattern is heterogeneous with larger involvement of frontal and temporal cortices in addition to subcortical nuclei mainly the putamen, thalamus, and nucleus accumbens. This loss of gray matter volume is thought to be due to shrink- age of neurons and loss of dendritic spines and synapses
.Table 3.1 Key Brodmann areas and their anatomical and functional correlates Brodmann area
(BA) Anatomical correlate Function
BA10 Frontal pole, medial and lateral Widely connected, complex social decision making and balancing BA9 Dorsolateral prefrontal cortex, mainly
lateral but some medial
Executive control area
BA8 Posterior to BA9 in lateral prefrontal cortex
Frontal eye field, executive function given its wide connections
BA6 Posterior portion of the lateral frontal area, just anterior to motor cortex
Motor initiation and programing, some language, memory and executive functions
BA46 Mid lateral prefrontal (middle frontal gyrus)
Involved in executive control of language (left) and in monitoring (right)
BA44, 45 Inferior aspect of lateral prefrontal area Make Broca’s complex, involved in language production (mainly in left dominant side) and some more complex aspects of language and pre-language behavior
BA47 Anterior inferior aspect of prefrontal area
Makes posterior part of orbital frontal cortex involved in language and social cognition
BA11 Base of the frontal pole Connected to other limbic structures and to executive areas, involved in initiation of behavior
BA4 Precentral (part of frontal lobe) Primary motor function BA1, 2, 3 Postcentral (part of parietal lobe) Primary sensory function
BA5 and 7 Superior parietal cortex Association sensory-motor areas, involved in cortical sensory processing BA40 Supramarginal, inferior parietal lobule Complex cognitive processing, connected with frontal executive areas,
part of central executive network
BA39 Angular gyrus, inferior parietal Involved in complex tasks including language, calculation, and spatial orientation
BA21 Middle temporal Involved in semantic, prosodic, and complex sound processing and deduc- tive reasoning
BA41 and 42 Superior temporal Primary auditory area
BA 13–16 Insula and temporal-insular junction Part of salience network, involved in somatic representation, pain (posterior), and affective processing (anterior)
BA31 Posterior cingulate cortex Part of the default mode network, involved in self- referential function BA25 Sub-genual cingulate cortex Involved in affective processing and depression
BA38 Temporal pole Involved in emotional processing
BA37 Medial aspect of inferior temporal area Facial recognition BA28 and 39,
BA35–36
Entorhinal area and perirhinal areas (medial temporal)
Memory and spatial function
BA17, 18, 19 Occipital cortex Primary, secondary, and association visual areas
BA24, 32, and 33 Anterior cingulate cortex Involved in salience network, connection between cognition and emotion, motivation
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Cingulate sulcus Superior frontal gyrus Paracentral lobule Marginal ramus of cingulate sulcus
Superior parietal lobule Precuneus
Parieto-occipital sulcus Cuneus
Calcarine sulcus Lingual gyrus Cerebellar cortex Dentate Cerebellar tongue Pons
Medulla oblongata Cingulate gyrus
Sub-genual gyrus Rectus gyrus
Caudate head
Putamen-thalamus Midbrain tegament Superior and inferior colliculi
Motor gyrus Central sulcus
Sensory gyrus Superior parietal lobule Supra-marginal gyrus Angular gyrus Parieto-occipital sulcus Occipital lobe Calcarine fissure Superior temporal gyrus Inferior temporal gyrus Calcarine fissure Mid frontal gyrus
Inferior frontal gyrus Obligue fissure Temporal pole
Superior frontal gyrus Insular cortex Inferior horn of lateral ventricle
Hippocampus Temporal pole a
b
.Fig. 3.1 Illustration of the main anatomical structures seen on T1 structural MRI images. a Medial view, b lateral view
rather than neuronal loss per se. There is also evidence for loss of myelinated axon length by up to 50%. These changes correlated with age-related cognitive changes like decline in processing speed, executive function, and episodic memory [17]. (See 7Chap. 4.) In a study of 54 healthy volunteers aged 20–86 years, gray matter loss during adult life seemed to have linear relationship with aging, while white matter loss accel- erates in middle age [18]. Although this study did not iden- tify difference in the rate of gray and white matter atrophy between the sexes, an earlier study did show that age-related shrinkage in some central nervous system domains (e.g.,
sulci, lateral fissure, cerebrospinal fluid volume, and in pari- etal-occipital areas) is more prominent in males compared to females [19]. Although brain volume change has been con- sidered “normal for age,” there is evidence that gray matter volume loss might be overestimated and is in fact linked to future cognitive decline especially in the prefrontal area [20, 21].Another change that has been considered as “normal for age” is an increase in white matter hyperintensities. It is esti- mated that one third of people over age 60 have white matter hyperintensities [22]. In addition to age, female gender, high
Neuroimaging in Clinical Geriatric Psychiatry
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.Table 3.2 Summary of the three main large-scale networks, their structure, and function
Network Anatomical structures Function
Default mode network (DMN) Medial prefrontal cortex (mPFC) Posterior cingulate cortex (PCC) Precuneus
Lateral parietal cortex
Introspection Self-referential
Central executive network (CEN), aka frontal-parietal network (FPN)
Lateral prefrontal cortex (lPFC) Intra-parietal cortex (including inferior parietal lobule)
Extrospection Task-related
Involved in cognitive tasks Salience network (SN), aka anterior
cingulo-insular network (aCIN)
Dorsal anterior cingulate cortex (dACC) Anterior insular cortex
Subcortical loop:
Striatum Globus pallidus Sub-thalamus Thalamus
Emotional network
Switch between DMN and CEN based on salience to the individual
Crossroad between several psychiatric illnesses Corpus callosum
Dorsal Splenum
Genu
Posterior cingulate (BA31)
c
d Anterior cingulate (BA32)
Sub-genual cingulate (BA25)
Medial prefrontal gyrus
Anterior limb of internal capsule Genu of internal capsule External capsule Sylvian fissure
Splenium of corpus callosum Lateral ventrical
Temporal lobe Parietal lobe Calcarine fissure Corpus callosum, anterior Internal capsule External capsule Sylvian fissure Lateral vantricles Anterior commissure Third ventricle Inferior horn Inferior lateral prefrontal gyrus
Anterior cingulate cortex Insular cortex
Caudate head Putamen Globus pallidus Thalamus
Posterior cingulate gyrus Occipital lobe
Head of caudate Insular gyrus
Putamen/globus pallidus Septal area
Nucleus accombence Superior, middle, and inferior temporal gyri
Amygdala-hippocampus Superior, middle, and inferior frontal gyri
.Fig. 3.1 (continued) c Closeup look at the cingulate gyrus with some Brodmann areas added for demonstration, and d transverse section (upper) and coronal section (lower) approximately at the level of the anterior commissure
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systolic blood pressure, and aortic atherosclerosis are other risk factors for white matter hyperintensities [23–25]. These changes in white matter can be seen in periventricular and/
or in deep white matter locations. Despite relatively similar appearance on MRI (T2 and FLAIR sequences; see below for description), the nature of these lesions is somewhat hetero- geneous in terms of histological nature including white mat- ter infarction, gliosis, or plaques of demyelination [26, 27].
The appearance of periventricular white matter hyperintensi- ties in terms of the irregularity of lesion edges is thought to be related to their histological nature, i.e., lesions with irregular edges tend to be ischemic in nature, while those with smooth edges are more related to gliosis and demyelination [28].
The above changes in brain structure likely contribute to modification in brain networks in old age. Detailed discus- sion of these changes is beyond the scope of this chapter.
Briefly, there are two main lines of research into cognitive network activity and connectivity with aging: task-related fMRI and resting-state fMRI. Task-related fMRI involves obtaining brain activation pattern as it is related to a cogni- tive task (i.e., event-related, like working memory and epi- sodic memory tasks). Several studies identified modification in fMRI BOLD (described below) signal during cognitive tasks in older compared to younger adults. Examples of these modifications include loss of cortical specificity (dedifferen- tiation), recruitment of wider network to achieve the same task (indicating compensation), and more involvement of frontal rather than posterior networks when performing the cognitive task. This sizeable literature resulted in several models to explain cognitive aging including scaffolding the- ory of aging and cognition (STAG) [29], system vulnerability view [30], and brain maintenance hypothesis [31].
Resting-state fMRI (rsfMRI) connectivity studies have the advantage of not being task-performance dependent, which makes them more feasible and less subject to vari- ability. Converging evidence suggests reduction in connec- tivity in large-scale networks including DMN, SN, and CEN networks with aging. This change correlates with cognitive changes with aging and is likely the result of changes in brain structure described above (please see [32] for review).