Functional Neuroanatomy and Essential Neuropharmacology

Question 1

The brain itself is divided into three main components:

Answer 1

The forebrain (cerebral hemispheres and diencephalon)

The midbrain

The hindbrain (comprised of the medulla, pons, and cerebellum, which together form a connection between the brain and spinal cord)

Question 2

“unimodal” cortex

Answer 2

processes information pertaining to a specific sensory modality

plays a prominent role in perception

Question 3

“polymodal” cortex

Answer 3

processes information received from disparate modalities through afferent connections

critically involved in higher-order conceptual processes that are less dependent on concrete sensory information than on abstract features extracted from multiple inputs

Examples of polymodal cortex include the convergence zones of the anterior temporal lobe and inferior parietal lobule.

Question 4

the frontal lobe can be further subdivided into:

Answer 4

The orbitofrontal/ventromedial region, important for emotional regulation, reward monitoring, and personality; damage to the orbitofrontal sector produces disinhibition, whereas damage to the ventromedial sector results in disordered reward/punishment processing and problems marking perceptual or learning experiences with reward value and emotional significance.

The dorsolateral region, important in a broad range of cognitive-executive functions; damage produces dysexecutive syndromes, impairments in working memory, and poor attentional control of behavior.

The dorsomedial region, important for intentional and behavioral activation; extensive damage to this region produces striking impairments in initiated behavior including akinetic mutism, in which the person is alert and awake (not comatose) but cannot move or speak.

Question 5

The temporal lobes can be divided roughly into three regions:

Answer 5

The temporal polar cortical areas, a polymodal convergence zone important for intersensory integration and semantic memory.

The ventral temporal areas, important for object recognition and discrimination; bilateral damage can produce object or face agnosia.

The posterior temporal region, comprised of the middle and superior temporal sulci, which contains the primary auditory areas and Wernicke’s area in the language-dominant hemisphere, important for language comprehension, and prosodic comprehension in the homologous non-dominant hemisphere.

Question 6

The parietal lobe can be divided into three regions:

Answer 6

The superior parietal lobe, important for sensory–motor integration, body schema, and spatial processing.

The temporoparietal junction, important for phonological and sound-based processing; language comprehension (left) and music comprehension (right).

The inferior parietal lobule, important for complex spatial attention, integration of tactile sensation, and self-awareness.

Question 7

The occipital lobe contains the primary visual cortex (surrounding the calcarine fissure) and the visual association cortex.

Complete damage to the primary visual cortex produces cortical blindness or (rarely) phenomena of Anton’s syndrome (denial of cortical blindness) or blindsight (detection of unconsciously perceived stimuli in the blind field).

Partial damage produces visual field defects that reflect the region of visual cortex damaged.

Answer 7

The occipital lobe is also the origin of the two main visual-cortical pathways:

The ventral visual pathway, connecting occipital and temporal lobe; important for object and face recognition, item-based memory, and complex visual discrimination.

The dorsal visual pathway, connecting the occipital and parietal lobes via the superior temporal sulcus; important for spatial vision and visuomotor integration.

Question 8

An important feature of the neocortex is its six-layer laminar structure, which distinguishes it from limbic cortex (archicortex), which has only three.

Answer 8

Each of the six layers has distinct input–output connections and, when examining any cortical region, evaluation of the region’s laminar structure provides important clues regarding that region’s function by elucidating other brain regions to which it is preferentially connected.

Question 9

Neuroanatomy of Vision

Answer 9

Retinal ganglion cells in each eye send their axons into the optic nerve, which projects posteriorly and comes together at the optic chiasm, where the optic tracts originate.

The majority of optic tract fibers terminate in the lateral geniculate nucleus (LGN) of the thalamus, which then projects to the primary visual cortex in Brodmann area (BA) 17 (“striate cortex”) in the occipital pole.

Question 10

Summary of the Anatomy of Memory

system contains two functionally and anatomically integrated circuits,

the medial (Papez) one involving the hippocampus

the lateral one involving the amygdala.

Answer 10

Amnesia is associated with medial temporal, thalamic, BF, and parahippocampal gyrus damage

functional impairment of more than one circuit is necessary for dense amnesia to occur.

Less severe forms of memory disturbance can
result from more restricted lesions that do not impair both circuits.

Question 11

Neuroanatomy of Language

The left hemisphere is dominant for language in more than 95% of right-handers and in more than 60–70% of left-handers.

The two regions implicated in Broca’s and Wernicke’s seminal cases lie adjacent to the Sylvian fissure separating the temporal and frontal lobes, and subsequent analyses of language disorders associated with these and associated regions have led to the concept of “perisylvian” aphasias.

Question 12

Perysylvian language system

Answer 12

anterior temporal convergence zone (semantic knowledge)

Heschl’s Gyrus primary auditory cortex

Wernicke’s area (BA 22)

Angular gyrus

Supramarginal gyrus

arcuate fasiculus

Broca’s area (BA 44)

sylvian fissure

Question 13

Syndrome: Broca’s Aphasia

Answer 13

symptom: ↓speech production; sparse, halting speech, missing function words, syntactic deficits, right hemiparesis (often)
deficit: Impaired speech planning and production

lesion location: Posterior aspect of third frontal convolution (damage to adjacent motor fibers may produce right hemiparesis)

Question 14

Syndrome: Wernicke’s

Answer 14

↓ auditory comprehension, fluent speech, paraphasias, poor repetition and naming, may have right homonymous hemianopia

Impaired representation of the sound structure of words

Posterior half of the superior (first) temporal gyrus (geniculostriate white matter damage may produce right homonymous hemianopia)

Question 15

Anomic Aphasia

Answer 15

↓single word production, marked for common nouns; repetition and comprehension relatively intact

Impaired storage or access to lexicon

Inferior parietal lobe or connections within perisylvian language areas; many other forms of aphasia evolve to anomia in recovery

Question 16

Transcortical Motor Aphasia

Answer 16

Disturbed spontaneous speech similar to Broca’s; relatively preserved repetition and comprehension

Disconnection between conceptual word/sentence representations in perisylvian region and motor speech areas

Deep white matter tracts connecting BA to parietal lobe; usually caused by anterior watershed infarcts

Question 17

Transcortical Sensory Aphasia

Answer 17

Disturbance in word comprehension with relatively intact repetition

Disturbed activation of word meanings despite normal recognition of auditorily presented words

White matter tracts connecting parietal and temporal lobe; usually caused by posterior watershed infarcts

Question 18

Conduction Aphasia

Answer 18

Disturbance of repetition and spontaneous speech, phonemic paraphasia

Disconnection between sound patterns and speech production mechanisms

Arcuate fasciculus; connections between Broca’s and Wernicke’s areas

Question 19

Neuroanatomy of Frontal/Executive Skills

Insight into the anatomic systems in which the frontal lobes participate can be gained by considering the following facts:

• Vast regions of the DLPFC have large granular layers (layer IV), suggesting strong and broadly distributed interactions with subcortical networks involving the thalamus.
• Architectonically, frontal cortex also contains regions with large layers II and III, suggesting the presence of extensive cortico-cortical connectivity.

Answer 19

frontal regions participate in extensive cortico-cortical networks

interacting with:

parietal lobe systems involved in attention, proprioception

visuomotor interaction with the environment

temporal lobe memory and emotional systems.

participate in reciprocal circuits involving the basal ganglia and thalamus.

Such interactions allow modulation and volitional control to be exerted on perceptual, emotional, and action systems toward the completion of goal-directed action.

Question 20

Core Architecture of Subcortical Loops in Frontal Lobe

Answer 20

cortex

striatum (caudate, putamen)

globus pallidus

thalamus

cortex

Question 21

Cortico-Striatal-Pallidal-Thalamo-Cortical Loops Most Relevant to Cognition

Answer 21

orbitofrontal (response-reward learning)

anterior cingulate / limbic (emotion regulation)

dorsolateral prefrontal (executive functions)

oculomotor (eye movement subserving cognition)

motor (motor control)

Question 22

Frontal Lobe Attentional Mechanisms

Posner and Rothbart (2007) indicate that there are three interconnected systems for attention:

one for orienting to stimuli
one for alerting
one for executive aspects of attention

Answer 22

Orienting refers to the tuning of perceptual systems to incoming stimuli so that relevant information from sensory input can be selected for further processing. It is primarily dependent on acetylcholine and involves a functional system consisting of the superior colliculus, pulvinar thalamic nucleus, posterior temporoparietal cortex, and a region within the frontal lobes known as the frontal eye fields (BA 8, involved in volitional control of eye movements).

Alerting is a state of sensitivity to incoming stimuli. It is modulated by norepinephrine and depends primarily on ascending sensory inputs from the thalamus.

Executive attention involves monitoring and resolving conflicts among thoughts, feelings, and behaviors. It is primarily dependent on dopamine and involves key structures including the anterior cingulate cortex and DLPFC.

Question 23

Frontal Lobes and Working Memory

Answer 23

Key anatomic facts concerning working memory can be summarized as follows:

A dorsal (spatial)–ventral (object-based) distinction appears to exist in frontal working memory systems just as it does in posterior cortex.

Dorsal components of the frontal working memory system are preferentially connected to structures in the dorsal visual stream and vice-versa.

Question 24

Major Neurotransmitter Systems of the Brain

Answer 24

Acetylcholine

• Attention, memory, regulation of thalamic output
• Attention, learning, memory

Norepinephrine/Noradrenaline

• attentional shifting; arousal
• mood, sleep-wake cycle

Serotonin

• mood, arousal
• pain, respiration, temperature, motor control

Dopamine

• motor regulation, thalamic gating
• memory, reward systems
• executive function, working memory, top down attention, motor initiation
• lactation, mentruation, sexual behavior

GABA
- broad neuromodulatory functions

Glutamate
- broad excitatory functions

Question 25

Akinetic mutism

Answer 25

A neurologic condition resulting from bilateral medial frontal lobe injury in which the patient does not move or speak but remains aware of ongoing events.

It can be seen in stroke syndromes, tumors of the olfactory groove, and in the final stage of certain neurodegenerative diseases.

Question 26

Anatomico-clinical correlation

Answer 26

The experimental or clinical method of establishing direct associations between anatomic damage to the brain and sensory, motor, emotional, or cognitive impairments. Such associations can be established through careful case analysis or experimental study and involve the use of both neuropsychological methods and techniques for characterizing and localizing lesions.

The core knowledge base of clinical neuropsychology depends in part on precise anatomico-clinical correlations.

Question 27

Basal forebrain (BF)

Answer 27

A group of structures located in the vicinity of the ventromedial frontal lobe, anterior to the caudate and putamen.

Comprised of the nucleus basalis, diagonal band of Broca, substantia innominata, and medial septal nuclei, it is the major source of cholinergic input throughout the brain.

Damage to the BF is associated with profound memory loss with confabulation, the latter of which is likely associated with neighboring frontal lobe damage.

Question 28

Brodmann areas

Answer 28

A region of cortex defined by its cytoarchitectonics (cellular structure and organization).

Fifty-two separate areas were described in this way by Brodmann in 1909 and have been refined through clinical and basic neuroscience research ever since.

The Brodmann system remains the most frequently cited, widely known, and generally useful system of cortical organization today.

Question 29

Cortico-cortical connections

Answer 29

In general, depictions of white matter connections within the brain adopt the form of “from (region)–to (region).”

Thus, cortico-cortical connections begin in one region of cortex and end in another.

Practically any connection can be depicted in this way.

Cortico-striatal connections project from a region of cortex to the striatum (caudate and putamen).

Thalamo-cortical projections start in the thalamus and project to cortex.

The route of a complex pathway can be similarly depicted, as in a cortico-striatal-pallidal-thalamo-cortical loop.

Fiber tracts can also be identified by reference to particular structures in which they are found or to the functions they perform.

For example, “commissural” fibers are found in the anterior commissure and corpus callosum, where they cross the midline and connect homologous areas in the right and left hemisphere.

“Association” fibers are short cortico-cortical connections linking primary sensory areas with their surrounding association cortices.

Question 30

Cortico-striatal-pallidal-thalamo-cortical loop

Answer 30

An essential feature of cortical-subcortical interaction in a variety of cognitive domains.

Cortical activity is modulated by connections from cortex, through inhibitory and excitatory structures in the basal forebrain and thalamus, and back to cortex as a way of engaging a cortical region needed for task performance or of inhibiting another region whose function would interfere with processing or compete for output.

The process of activating cortical regions for task performance is known as selective engagement.

Question 31

Disconnection theory

Answer 31

A prominent anatomico-clinical theory in neuropsychology which describes certain neurobehavioral syndromes as the result of damage to white matter connections as opposed to cortical processors.

The resulting syndrome occurs because two or more normally functioning processors are incapable of cooperating in performing a complex task because their connections have been severed.

Prominent disconnection syndromes include:

• alexia without agraphia
• optic aphasia
• impaired naming of objects in the left hemispace due to callosal disconnection of the right hemisphere from left- hemisphere language regions.

Question 32

Dorsal/ventral visual systems

Answer 32

After being processed in primary visual area and unimodal visual association cortex, visual information takes two distinct routes in interacting with other, more anterior cortical regions.

A ventral route courses through the inferior temporal lobe and is important for form and object identification.

A dorsal route courses through the superior temporal cortex and parietal lobe and is important for spatial processing and visuomotor interaction.

The “two visual systems” concept is highly influential in contemporary neuroscience and accounts for a variety of neuropsychological syndromes, including visual agnosia, spatial neglect, and attentional dysfunction.

The “dorsal-ventral” distinction also appears in other anatomic regions, including working memory systems in the frontal lobe, suggesting that this anatomic feature of brain organization may have widespread functional implications.

Question 33

Excitotoxicity

Answer 33

A pathological process by which nerve cells are damaged or destroyed by excessive stimulation by neurotransmitters such as glutamate.

It is thought to be a key factor in the CNS response to spinal cord injury, traumatic brain injury, and neurodegenerative disease.

It may also be involved in CNS injury after medical events such as hypoglycemia and status epilepticus.

Question 34

Lateral limbic circuit

medial limbic circuit

Answer 34

One of two limbic circuits subserving memory in the medial temporal lobe, diencephalon, and frontal lobe.

The circuit is as follows:

Amygdala → dorsomedial thalamic nucleus (via amygdalofugal pathway) → orbitofrontal lobe → amygdala (via uncinate fasciculus).

It must be damaged along with the medial limbic circuit for dense amnesia to occur.

Question 35

Medial limbic circuit (Papez circuit)

Answer 35

This circuit, described by Papez in 1938 in the context of emotion, is one of two limbic circuits subserving memory in the medial temporal lobe and diencephalon.

The circuit is as follows:

Hippocampus → mammillary bodies (via the fornix) → anterior thalamic nucleus (via the mammillothalamic tract) → cingulate gyrus → hippocampus (via cingulum and parahippocampal cortex).

It must be damaged along with the lateral limbic circuit for dense amnesia to occur.

Question 36

Neurogenesis

Answer 36

The birth and proliferation of new neurons, most active during pre- and perinatal development. In certain regions of the brain (e.g., dentate gyrus of the hippocampus), neurogenesis continues into adulthood and is thought to be a critical basis for the formation of new memories and for experience-dependent neuroplasticity.

Question 37

Neuroplasticity/synaptic plasticity

Answer 37

Changes in neural pathways and synapses due to changes in behavior, environment, or neurochemical processes.

Neuroplasticity is critical to normal development of CNS-dependent abilities and is critical to recovery from brain damage.

The concept of the brain as a “plastic” organ has replaced earlier conceptualizations that no further structural development or repair was possible after a certain point in development and is an important idea in contemporary advancements in recovery of function, neurorehabilitation, and neural repair.

The concept of “experience-dependent neuroplasticity” refers to changes that result from exposure to enriched environments, behavioral practice, or other environmental stimulation.

Question 38

Trisynaptic circuit

Answer 38

The pattern of synaptic transmission within the hippocampus, which describes three linearly organized synapses.

The circuit is as follows:

Entorhinal cortex → dentate gyrus (DG) via the perforant path (synapse 1), DG → CA3 via mossy fibers (synapse 2), CA3 → CA1 via Schaffer collaterals (synapse 3).

Although a simple and easily comprehended pathway, recent anatomic work has found many complexities to this presumed structure and has questioned whether it appropriately represents the actual pathway by which information is transmitted and processed within the hippocampus, or whether the function of the medial temporal lobe memory system is the result of densely reciprocal interconnections between and within structures.

Question 39

Two-system theory of amnesia

Answer 39

The contemporary viewpoint that argues that the necessary and sufficient lesion producing human amnesia involves damage to two limbic circuits, one (medial) involving the hippocampus, and the other (lateral) involving the amygdala.

According to this view, dense amnesia occurs only when both circuits are damaged, whereas less severe memory impairment may occur with partial damage.

This theory provides an integrative account of how and why amnesia can be produced by lesions to the medial temporal lobe, diencephalon, and basal forebrain structures.

Question 40

Unimodal/polymodal cortex

Answer 40

Cortex devoted to processing information within a specific sensory modality (vision, audition, tactile).

Thus, for example, areas 17–19 are unimodal visual cortex.

Unimodal association cortices, located adjacent to primary sensory areas, eventually project to regions of cortex that integrate information from multiple modalities, enabling more complex modes of thought including semantic processing.

These convergence regions are referred to as heteromodal or supramodal because the nature of their processing utilizes and develops representations that go beyond simple sensory input channels.

Question 41

You are looking at a slice of a brain scan that is oriented so that it depicts one hemisphere with the frontal lobe on the left of the scan and the occipital lobe on the right. You are looking at a ____.

Answer 41

sagittal slice The scan is described such that you are looking at the brain from the side.

As described, the cut must be sagittal, perpendicular to the ground and running in a rostral-caudal (anterior-posterior) plane.

Question 42

The parietal lobe is ____ to the temporal lobe.

Answer 42

dorsal

Dorsal means “toward the back” in the spinal cord, but above the brainstem, the neuraxis undergoes a 90-degree bend such that its meaning in the brain is essentially “superior” or” upper.” Caudal means “toward the front,” or “anterior” in the brain. Thus, dorsal is the only possible answer to this question.

Question 43

A patient with a lesion of the ventral occipitotemporal area is most likely to experience an impairment in ____.

Answer 43

face recognition

The ventral occipitotemporal area refers to that region of cortex at the border between visual association area and posterior temporal lobe.

Reference to the “ventral” portion of this region means that it is part of the ventral visual pathway, which is important for object, face, and form/shape recognition.

Question 44

Which of the following is a cortical region directly implicated in episodic memory processing?

Answer 44

perirhinal cortex

The perirhinal cortex is on the basolateral temporal lobe surface and is one of the neocortical regions that project to the hippocampal memory system.

It, along with the parahippocampal cortex, was implicated in memory in a second-generation animal model proposed after Mishkin by Zola- Morgan and colleagues.

The hippocampus cannot be the correct answer because it is not a cortical structure.

Question 45

Which of the following structures is not part of the diencephalon?

hypothalamus

epithalamus

extended amygdala

subthalamus

Answer 45

extended amygdala

All structures within the diencephalon end with “thalamus” so the extended amygdala is the only possible answer.

Question 46

The classic interpretation of conduction aphasia is that it involves damage to the ____, thus disconnecting Broca’s and Wernicke’s areas.

Answer 46

arcuate fasciculus

Conduction aphasia involves a disruption of repetition with relatively spared verbal comprehension and verbal fluency.

The classic interpretation is a disconnection between Broca’s and Wernicke’s areas, both of which are relatively intact.

Question 47

Regions that appear important for mapping sounds to meaning in language include ____.

Answer 47

the supramarginal and angular gyri

These cortical regions provide an interface between Wernicke’s area and polymodal cortical areas that process meaning/semantics.

Question 48

Dysfunction of the mesolimbic dopamine pathway has been associated with ____.

Answer 48

impaired reward functioning

Mesolimbic dopamine depletion has been associated with impaired reward functioning and overactivation of this system has been associated with positive, not negative symptoms of schizophrenia.

Bradyphrenia is associated with impairment in mesostriatal, not mesolimbic, dopamine.

Nonfluent aphasia is not specifically associated with the dopaminergic systems per se.

Question 49

Tell me about glutamate?

Answer 49

It is the most abundant excitatory neurotransmitter in the brain.

Too much glutamate can cause excitotoxicity and cell death.

Glutamate has been implicated in stroke and Alzheimer’s disease.

Glutamatergic activity stimulates, rather than inhibits, new memory formation.

Question 50

In the brain (above the spinal cord), “ventral” means the same as ____.

Answer 50

inferior

The planes of section take a 90-degree turn above the spinal cord, such that what is “ventral” (toward the front) in the lower body is now “inferior” (toward the bottom) in the brain.

Question 51

A piece of cortex with a very large layer IV most likely ____.

Answer 51

is from a sensory region

A large Layer IV indicates extensive input from the thalamus, which would not be characteristic of cholinergic neurons generally and would not be characteristic of neurons in the motor strip or basal ganglia.

Question 52

Which of the following is not part of the basal forebrain?

septal area

dorsomedial nucleus

substantia innominata

red nucleus of the stria terminalis

Answer 52

dorsomedial nucleus

The dorsomedial nucleus is part of the thalamus, not the basal forebrain.

All of the other structures are part of the basal forebrain.

Question 53

Fluent aphasia results from lesions in the ____.

Answer 53

posterior left temporal lobe

Posterior lesions are associated with fluent aphasic syndromes.

Question 54

Bilateral damage to the DLPFC produces ____.

Answer 54

a disorder of executive attention

Apathy and akinetic mutism would be produced by lesions to the medial sector of the frontal lobe

disinhibition would be produced by orbitofrontal lesions.

Top- down (executive) attention is the only alternative associated with DLPFC function.

Question 55

Lesions in the superior (dorsal) aspects of the DLPFC produce deficits in ____.

Answer 55

spatial working memory

The text describes how working memory may be organized in a way similar to posterior cortex in terms of spatial vs. object-based processing.

More dorsal lesions in DLPFC tend to produce problems in spatial, as opposed to object-based working memory, just as lesions in dorsal parietal lobe tend to produce disorders dominated by spatial dysfunction.