ABSTRACT
A. Anatomic Classification 1. Idiotypic primary cortex (sensory or motor, e.g., primary
visual cortex) a. Initial cortical processing of afferent sensory input or
source of primary motor efferents b. Modality-specific c. Directly connected with association cortices and subcor-
tical modulating nuclei (e.g., basal ganglia, thalamus) 2. Homotypic unimodal association cortex
a. Usually anatomically close to respective primary cortex; modulates the function of primary cortex
b. Modality-specific c. Directly connected not only to respective primary cortex
but also with heteromodal association cortex (convergence of pathways) and subcortical modulating nuclei (e.g., basal ganglia, thalamus)
3. Homotypic heteromodal (multimodal) association cortex a. Directly connected with each other and unimodal associ-
ation cortices (including the limbic and paralimbic regions)
b. Two major areas 1) Anterior heteromodal association area (prefrontal cor-
tex): concerned with planning of movements and executive functions
2) Posterior heteromodal association area (parietotemporal
areas, junction between parietal, temporal, and occipital lobes): visuospatial perception and language
4. Limbic and paralimbic cortex a. Corticoid areas: basal forebrain (primitive organization
without discernable lamination in some areas; least differentiated) 1) Amygdala complex 2) Septal nuclei 3) Substantia innominata (basal nucleus of Meynert)
b. Allocortex 1) Hippocampal complex and piriform or primary
olfactory cortex (paleocortex) 2) One or two bands of neurons arranged in external
and internal pyramidal layers c. Mesocortex (paralimbic structures)
1) Parahippocampal region 2) Orbitofrontal cortex 3) Temporal pole 4) Insula 5) Cingulate cortex
B. Histology 1. Cell types
a. Pyramidal cells 1) Pyramidal-shaped cells with apical dendrites extending
toward cortical surface 2) “Projection neurons” involved in transmitting signals
to other cortical, subcortical, or spinal areas 3) Located mainly in layers III, V, and VI 4) The neurotransmitter is glutamate (excitatory)
b. Stellate cells 1) Star-shaped neurons with dendritic extensions in all
directions 2) Found in all layers, but most common in layer IV 3) Are local inhibitory interneurons; use γ-aminobutyric
acid (GABA) c. Fusiform cells
1) Found primarily in layer VI
Primary cortices do not communicate directly with each other
Heteromodal areas are responsible for integration of cortical processes and input from unimodal association areas, which in turn receive input from primary cortices
2) Long dendritic processes extend toward cortical surface
3) Axons project primarily to thalamus 2. Horizontal cortical organization
a. Neocortex (primary, unimodal, and heteromodal areas) is organized in six layers 1) Layers I to IV receive afferents 2) Layer V projects to spinal cord, brainstem, and basal
ganglia 3) Layer VI projects to thalamus 4) Corticocortical connections: mainly from layers II
and III of primary cortices to layers V and VI of association cortices
b. Layer I-molecular (plexiform) layer: consists mainly of local interneurons and apical dendrites of pyramidal cells in deeper layer
c. Layer II-external granular layer 1) Stellate cells: axons project to deeper cortical layers 2) Pyramidal cells: axons project to contralateral cortex
as commissural fibers d. Layer III-external pyramidal layer: pyramidal cells
with projections to ipsilateral cortices (association fibers) or contralateral hemisphere (commissural fibers)
e. Layer IV-internal granular layer 1) Consists mainly of stellate cells 2) Receives afferent glutaminergic input from thalamus 3) Prominent layer in primary sensory cortices
f. Layer V-internal pyramidal layer 1) Pyramidal cells: axons project to basal ganglia, brain-
stem, spinal cord, and contralateral cortex (commissural fibers)
2) Prominent layer in primary motor cortex, which contains giant pyramidal cells of Betz
g. Layer VI-multiform layer: pyramidal cells with projections to thalamus and layer IV
3. Vertical (columnar) cortical organization a. Each column is a functional unit of cortex b. Specificity of connection with target cells is maintained
and afferent feedback from the same target is received c. Layer IV is the main input layer in each column d. Afferents from a specific group of neurons in thalamus
project to a designated cortical column (layer IV): the organizational specificity of neuronal columns is mirrored in subcortical modulating nuclei (e.g., thalamus, basal ganglia)
4. Intercortical connections a. Association fibers: connection between different cortices
in same hemisphere 1) U-fibers (short association fibers) 2) Superior longitudinal fasciculus
3) Cingulum (part of the Papez circuit) 4) Inferior longitudinal fasciculus 5) Uncinate fasciculus
b. Commissural fibers: connection between the two cerebral hemispheres 1) Corpus callosum 2) Anterior commissure 3) Posterior commissure 4) Hippocampal commissure
c. Projection fibers: corticosubcortical fibers
C. Cortical Localization 1. Frontal lobe
a. Primary motor cortex (Brodmann area 4, M I) 1) Type: idiotypic primary cortex 2) Voluntary discrete movements involving direct projec-
tions to spinal cord anterior horn cells and subsequent direct activation of a motor unit
3) Lesion: contralateral pattern of upper motor neuron weakness a) Acute lesion: hypotonic and flaccid b) Chronic lesion: spastic, increased reflexes
4) Stimulation or epileptic activity: partial motor seizures with spread (jacksonian march) reflect somatotopic organization of the area
b. Premotor areas (area 6, M II) 1) Type: homotypic unimodal cortex 2) All areas project to primary motor cortex and spinal
cord 3) All receive projections from parietal cortex: parieto-
premotor pathways are important in goal-directed movements (reaching and grasping)
4) Divisions a) Ventral and dorsolateral premotor cortex
i) Located on lateral aspect of frontal lobe anterior to M I
ii) Input from parietal lobe and medial premotor areas
iii) Responsible for initiating motor plans in response to sensory stimuli (e.g., stopping at a red light)
iv) Involved in learning to associate a particular sensory stimulus with a particular motor movement (associative learning)
b) Supplementary motor cortex (medial premotor area, area 6, M II) i) Located on medial aspect of frontal lobe anterior
to M I ii) Input from ipsilateral parietal lobe and pre-
frontal “presupplementary area” iii) Presupplementary area is responsible for learning
sequences of a motor plan and supplementary motor cortex is responsible for producing the motor sequence already learned-does not initiate motor plans in response to sensory stimuli as the lateral premotor regions do
iv) Blood flow to supplementary motor cortex increases when one is thinking about or planning a movement
v) Contains complete bilateral somatotopic representation of the body
vi) Responsible for coordinating and advance planning of movements on the two sides of the body
vii) Stimulation/epileptic activity: tonic abduction and external rotation/elevation of the contralateral arm with forced head turn toward elevated arm (fencing posture)
c. Frontal eye fields (homotypic unimodal cortex): voluntary conjugate horizontal eye movements (lesion: transient paralysis of contralateral gaze)
d. Broca’s area 1) Receives connections from Wernicke’s area via arcuate
fasciculus 2) Projects to premotor areas involved in motor programs
required for speech production 3) Lesion: nonfluent aphasia, typically involving deficits
in both language production and motor speech outputs 2. Prefrontal lobe
a. Type: homotypic heteromodal cortex (all three regions discussed below)
b. Dorsolateral prefrontal cortex 1) Located on convexity of the gyri anterior to areas 8
and 45 2) Interconnects with other heteromodal regions, basal
ganglia, and dorsomedial thalamus 3) Important for executive functions, planning, judgment,
problem-solving 4) Lesion: poor abstract thought, poor planning, poor
judgment and problem solving, psychomotor retardation, motor impersistance and perseveration, poor executive functioning, and dysexecutive syndrome
c. Orbitofrontal cortex 1) Located on inferior surface of frontal lobes and
includes the frontal poles 2) Widespread interconnection with limbic system and
basal ganglia 3) Responsible for emotional and visceral activities,
social behavior, and inhibition of inappropriate behavior in a particular social context as well as judgment
4) Responsible for conscious perception of smell:
receives input from piriform cortex via thalamic relay 5) Impairment: disinhibited, impulsive behavior; poor
judgment and insight; emotional lability; euphoria and excessive and inappropriate laughter and jocular affect, especially with right hemispheric lesions; speech apraxia; environmental dependency syndrome with utilization; perseveration; hyperorality; hypersexuality
6) Impairment also associated with obsessive-compulsive behavior
7) Lesions of orbitofrontal cortex a) Meningioma: commonly involving the sphenoid
wing or olfactory groove b) Closed head injury: usually affecting orbitofrontal
and anterior temporal areas because of the irregular surface of the anterior and middle cranial fossae
8) Stimulation/epileptic activity a) Motor and gestural automatisms that may be com-
plex (bicycling, walking around the room) b) Olfactory hallucinations and forced thinking with
anterior frontopolar focus d. Mesial frontal cortex and anterior cingulate cortex
1) Interconnections with limbic system (especially amygdala)
2) Important role in initiation, motivation, and goaloriented behavior
3) Impairment: abulia, indifference, poor speech output, impaired initiation of a behavior or motor movement with reduced spontaneous movements; associated with urinary incontinence and gait disturbance
4) With severe impairment: akinetic mutism (no spontaneous behavior)
5) Anterior cerebral artery distribution strokes or
ruptured anterior communicating artery aneurysms can selectively involve mesial frontal structures
6) Stimulation/epileptic activity: complex motor and gestural automatisms
e. Wisconsin Card Sorting Test 1) Sensitive measure of function of prefrontal cortex 2) The subject is asked to sort the cards according to a
certain perceptual attribute of a visual stimulus (e.g., color, form, number) and, then, challenges the subject to shift cognitive sets without warning
3) Patients with frontal lobe lesions have difficulty with this task because of poor cognitive flexibility and perseveration)
3. Parietal lobe a. Primary somatosensory cortex (S I, postcentral gyrus):
idiotypic primary cortex b. Secondary somatosensory cortex (S II) on the parietal
operculum (on superior lip of sylvian fissure): homotypic unimodal cortex 1) Direct input from thalamus and postcentral gyrus
(S I) 2) Bilateral receptive fields (mostly contralateral),
receives and integrates information from both sides of the body
3) Provides somatosensory input to motor cortex 4) Projections to limbic system: important for tactile
learning c. Dorsal M pathway: occipitoparietal visuospatial pathway
responsible for visuomotor tasks (see below) d. Impairment
1) Lesion of primary somatosensory cortex (S I): primary somatosensory deficits (e.g., touch, vibration, joint position, stimulus localization), sparing pain and temperature sensations, which are projected to second somatosensory cortex (S II)
2) Lesion of S II at parietal operculum: pseudothalamic syndrome a) Impairment of pain and temperature (may have
complete loss of elementary sensory modalities) b) Syndrome of delayed pain and paresthesias, as may
occur sometimes with thalamic infarcts 3) Parietal somatosensory association cortices
a) Complex somatosensory functions b) Lesions produce “cortical sensory deficits” (e.g.,
two-point discrimination, graphesthesia, stereognosis, and recognition of bilateral simultaneous stimulation)
4) Impairment of nondominant hemisphere: anosognosia, dressing apraxia, geographic agnosia, constructional apraxia, hemispatial sensory neglect
Lesions of Prefrontal Cortex Dorsolateral: poor executive functions, planning, judgment, and problem solving
Orbitofrontal: disinhibition, impulsive behavior, poor judgment and insight
Medial frontal and anterior cingulate Abulia, indifference, poor speech output, impaired initiation of a behavior or motor movement with reduced spontaneous movements
Associated with urinary incontinence and gait disturbance
5) Lesions of dominant hemisphere: finger agnosia, acalculia, agraphia, alexia, aphasia (primarily conduction aphasia and/or transcortical sensory aphasia), right-left disorientation, conduction apraxia a) Angular gyrus syndrome (lesion of angular gyrus,
heteromodal cortex): anomia, alexia, constructional difficulties, acalculia, dysgraphia, finger anomia, right-left disorientation (aphasia may be present if lesion extends to superior temporal gyrus and Wernicke’s area)
b) Gerstmann’s syndrome: acalculia, dysgraphia, finger anomia, right-left disorientation
6) Lower homonymous quadrantanopia from damage to optic radiations (if lesion extends deep enough)
7) Balint’s syndrome: optic ataxia, ocular apraxia, simultanagnosia (bilateral lesions)
8) Reduced slow phase of optokinetic nystagmus 4. Temporal lobe
a. Primary auditory cortex (idiotypic primary cortex) 1) Located on dorsomedial aspect of superior temporal
gyrus 2) Has a well-defined tonotopic map reflecting cochlear
organization 3) Unilateral lesions do not cause hearing loss, but
subject may have difficulty localizing sound stimuli in space, especially from the opposite side
b. Auditory association cortex (homotypic unimodal cortex): no well-defined tonotopic map
c. Wernicke’s area d. Middle and inferior temporal lobes: memory and learning e. Limbic area: inferior and medial temporal areas f. Uncus receives olfactory and gustatory input g. Subcortical occipitotemporal projections and optic
radiations (Meyer’s loop) h. Insular cortex: taste area II (taste area I is on dorsal aspect
of lateral sulcus near insular cortex) i. Impairment
1) Superior homonymous quadrantanopia 2) Cortical hearing loss with bilateral temporal (or sub-
cortical) lesions 3) Auditory agnosia with lesions of bilateral, more than
unilateral, temporal cortex (and/or corresponding subcortical areas): difficulty recognizing different sounds (nonverbal auditory agnosias may also result from right-sided lesions)
4) Dysacusis: perception of particular sounds as unpleasant
5) Pure word deafness (often bilateral lesions) a) A verbal auditory agnosia (due to auditory-verbal
disconnection)
b) Patients can hear and react to environmental auditory cues and can understand written language, but are unable to understand spoken language
6) Wernicke’s aphasia (dominant lesions) 7) Klüver-Bucy syndrome: bilateral anterior temporal
lobe lesions (see below) 8) Amnesia
a) Nondominant hemisphere: amnesia for nonverbal, visuospatial information
b) Dominant hemisphere: amnesia for verbal information)
9) Amusia a) Example of nonverbal auditory agnosia b) Difficulty with recognition of songs, primarily
because of disturbance of recognition of different characteristics of music composition (e.g., rhythm, pitch, tone) due to right temporal lobe lesions
c) Left temporal lobe lesions: not true amusia, patient has difficulty understanding lyrics
d) Left temporal lobe lesions in musicians who analyze different aspects of music composition may produce some degree of amusia
10) Ageusia (lack of taste): possibly occurs with bilateral lesions of insular cortex
11) Semantic dementia: dominant anterior temporal lobe is site of word meaning (object-word associations)
12) Prosopagnosia (defined below) a) Lesion in posteroinferior temporo-occipital region b) Usually bilateral lesions, but nondominant hemi-
sphere lesion may be sufficient j. Stimulation/epileptic phenomena
1) Complex visual hallucinations of people, animals, etc. from a posterior temporal lobe epileptic focus
2) Auditory hallucinations 3) Olfactory hallucinations (especially unpleasant odor,
“uncinate fits”), gustatory hallucinations, epigastric rising sensation, intense fear (or pleasure), usually associated with alteration of consciousness and associated with complex partial seizures arising from medial temporal lobe
4) Alternation of memory a) Déjà vu: sensation of familiarity with a previously
unfamiliar experience, place, or event b) Déjà entendu: sensation of familiarity with a
previously unfamiliar auditory experience (e.g., sound, music, speech, or narrative)
c) Jamais vu: sensation of unfamiliarity with a previously familiar experience, place, or event
d) Jamais entendu: sensation of unfamiliarity with a previously familiar auditory experience
symptoms such as amaurosis, scotoma, or visual field defects)
b) Eye deviation, nystagmoid eye movements
5) Palinopsia a) Recurrence of an image no longer present in visual
field b) May occur with posterior temporo-occipital
epileptic focus 6) Automatisms are associated with the complex partial
seizures arising from, or spreading to, mesial temporal lobe
7) Postictal cough 5. Occipital lobe
a. Primary visual (striate) cortex (V1) 1) Type: idiotypic primary cortex (area 17) 2) Located along the banks of calcarine fissure 3) Layer IV
a) Receives the majority of input from lateral geniculate nucleus
b) Projects primarily to layers II and III, which then project to association cortices
4) Projections to superficial layer of superior colliculus and pulvinar: responsible for production of saccades and rapid shifting of gaze to another point in the visual field in response to a novel stimulus a) Other sensory cortices project to deep layers of
superior colliculus b) Superior colliculus acts as a sensory integration center c) Novel visual stimuli
i) Retinal ganglion cells and primary visual cortex project to superior colliculus (e.g., moving vehicle entering the far right visual field)
ii) Other sensory input (e.g., auditory-projections from corresponding primary sensory [auditory] cortex) to deep layers of superior colliculus
iii) Superior colliculus: integrated sensory response to direct gaze toward novel stimuli
5) Occipital pole: central (macular) vision 6) More anterior portions of calcarine cortex: peripheral
vision 7) Impairment
a) Homonymous hemianopsia: may or may not spare macular area (vascular lesions often spare the macula because of dual blood supply)
b) Anton’s syndrome: bilateral lesions of medial occipital lobe (usually acute onset) cause cortical blindness associated with denial of the deficit, of which the patient is unaware, and confabulation
8) Stimulation/epileptic phenomena a) Simple elementary visual hallucinations, primarily
geometric shapes and patterns (usually bright, colorful, positive symptoms, but may be negative
Important Cortical Syndromes Angular gyrus syndrome
Dominant angular gyrus lesion Anomia, alexia, constructional difficulties, acalculia, dysgraphia, finger anomia, right-left disorientation ± aphasia
Gerstmann’s syndrome Dominant angular gyrus lesion Acalculia, dysgraphia, finger anomia, right-left disorientation
Anton’s syndrome Bilateral medial occipital lobe lesion Cortical blindness associated with denial of the deficit, for which the patient is unaware, and confabulation
Balint’s syndrome Lesion involves occipitotemporal pathways bilaterally, often seen with Alzheimer’s disease
Optic ataxia, ocular apraxia, simultanagnosia Klüver-Bucy syndrome
Bilateral anterior temporal lobe lesion Hyperorality and oral exploratory behavior, altered eating habits, weight gain, emotional blunting, blunting of response to fear and aggression, and altered sexual activity (hyposexuality > hypersexuality)
Fregoli syndrome Belief that the strangers are identified by the patient as familiar
Usually seen in context of dementia Capgras’ syndrome
Belief that a family member is an imposter Usually associated with paranoid delusions in the context of dementia
Ganser syndrome “Syndrome of approximate answers”; answers are consistently nearly correct but not correct
Usually seen in context of psychiatric disease and malingering but may also be seen in degenerative dementias
Charcot-Wilbrand syndrome Impaired ability to produce an internal image of a named object
b) Follows the ventral pathway to inferior temporal cortex
c) Concerned primarily with perception of form and color; important in recognition of faces and objects and pattern identification
d) P cells do respond to changes in color contrast e) Impairment of ventral P pathway can cause the
following: i) Aperceptive visual agnosia: cannot recognize
objects by visual presentation or draw the objects (cannot perceive the objects); lesions usually involve occipital or bilateral occipitotemporal projections; this is in contrast to associative visual agnosia in which perception is intact and patient can draw the object but is unable to visually recognize the object (the latter disturbance may be seen in lesions involving the posterior parietal area, sparing the cortices responsible for perception)
ii) Achromatopsia: cortical color blindness occurring with lesions of inferior occipitotemporal
b. Visual association areas (peristriate cortices) 1) Type: homotypic unimodal cortex 2) Located in the peristriate occipital areas (areas 18 and
19) and middle and inferior temporal gyri (areas 20, 21, 37)
3) Synthesis of visual input including perception of different aspects of visual input as well as perception of motion and integration with other sensory modalities
4) Parallel pathways: projections to parietal and temporal lobes
5) Dorsal M pathway (“where pathway”) (Fig. 7-2) a) Originates in M cells of retina that project to mag-
nocellular portion of lateral geniculate nucleus b) Follows dorsal pathway to middle temporal (MT)
and medial superior temporal (MST) areas to reach the posterior parietal area i) MT and MST were originally defined in mon-
key brains; the anatomic correlate in human brain is primarily the junction of occipital, parietal, and temporal lobes
ii) Bilateral lesions of MT can cause motion agnosia (akinetopsia), inability to perceive motion
c) M cells do not respond to change in color contrast, but MT neurons are sensitive to color analyzed primarily in the P pathway
d) M pathway carries information on perception of depth, analysis of motion, and spatial orientation (“where”) of a particular visual input
e) Important for reaching and grasping (visuomotor tasks, transmits information about the location of an object in space): impairment causes optic ataxia (impaired visually guided reaching and grasping)
f) Important role in shifting direction of gaze in response to visual stimuli: impairment causes ocular apraxia
g) Important for understanding the meaning of an image as a whole: impairment results in simultanagnosia while perception of different components of the object remains intact
h) Balint’s syndrome: the combination of optic ataxia, ocular apraxia, and simultanagnosia (usually occurs with bilateral lesions)
i) Other signs of impairment: abnormal depth perception, unilateral or bilateral inferior quadrantanopia, abnormal slow component of optokinetic nystagmus
6) Ventral P pathway (“what pathway,” Fig. 7-2) a) Originates in P cells in retina that project to parvo-
cellular portion of lateral geniculate nucleus
projections in the P pathway (nondominant hemisphere or bilateral) and accompanied by a superior quadrantanopia because the lesion involves inferior striate cortex (inferior to the calcarine sulcus) or inferior temporal projections
iii) Color agnosia: patient can read color plates but cannot name colors; intact knowledge of colors (e.g., patient knows that the color of sky is blue)
iv) Prosopagnosia: difficulty recognizing familiar faces and objects, lesion involves occipitotemporal areas unilaterally (right-sided) or bilaterally affecting fusiform gyri
v) Difficulty revisualizing the characteristics and appearance of objects and people
vi) Unilateral or bilateral superior quadrantanopia
A. Definition: (arousal, attention, and awareness of self and the environment)
B. Basic Anatomy of Consciousness 1. Ascending reticular activating system
a. Brainstem reticular formation: complex aggregates of medium-sized neurons, most distinctive organization is in medulla and caudal pons
b. Neurons have long dendrites generally radiating perpendicular to brainstem tegmentum
c. Receives extensive input from major somatic and sensory pathways, including cerebral cortex, for modulation of activity
d. Projects to cerebral cortex directly or via thalamic relay to modulate cortical activity
e. Interconnections between thalamus and cerebral cortex
(cortico-thalamo-cortical loops) are important for coordinating cortical activity and processing sensory input
f. Midbrain reticular formation most important for arousal 1) Projections to basal forebrain and diencephalon are
the anatomic substrate for arousal 2) Lesion may cause alpha coma
g. Three functional divisions 1) Efferents to thalamic reticular nucleus (which then
sends inhibitory projections to other thalamic nuclei) 2) Efferents to hypothalamus and basal forebrain 3) Diffuse cortical projections, mainly from raphe nuclei
(serotonergic) and locus ceruleus (noradrenergic) h. Three anatomic divisions
1) Midline (raphe) 2) Lateral (mainly receives afferent input) 3) Medial (mainly responsible for efferent output)
i. Neurochemically defined divisions 1) Cholinergic neurons
a) Basal forebrain cholinergic neurons: important in attention, regulation of behavior, learning, memory
b) Mesopontine tegmentum cholinergic neurons: projections to thalamus and brainstem; important in regulation of arousal and REM sleep
2) Serotonergic neurons a) Located in raphe nuclei of brainstem midline b) Reduced firing rate with transition from awake
state to sleep 3) Noradrenergic neurons
a) Located in pons and medulla b) Largest group is in locus ceruleus (in pons) c) Responsible for regulation of arousal
Achromatopsia Cortical color blindness
Lesions of the occipital lobe inferior to the calcarine sulcus, essentially involving the inferior occipitotemporal projections, produce a superior visual field defect and loss of color vision in the preserved inferior visual field (color perception of both the superior and inferior visual fields are affected, but the superior visual field defect masks the achromatopsia of the superior field)
Prosopagnosia Patients fail to identify faces and objects (the latter is more difficult when there are many members in a particular category)
Identification of a unique object (e.g., “my car”) is particularly difficult
Visual identification of famous individuals and those familiar to the patient is difficult, and patients may use other cues, such as voice or a unique physical characteristic, to identify the person
No difficulty identifying sex, age, and emotional state
Lesion localizes to the right fusiform gyrus or, more commonly, to fusiform gyri bilaterally
d) Responsible for global release of norepinephrine, which modulates and enhances arousal
e) Neurons of locus ceruleus increase firing in response to presentation of stimuli i) Selective phasic activation for focused selective
attention ii) High persistent activation associated with
distractibility and increased emotional reactivity 4) Histaminergic neurons
2. Thalamus a. Relay neurons: reciprocal connections with cerebral
cortex b. Reticular nucleus: local inhibitory projections to mainly
other thalamic nuclei 3. Basal forebrain
a. Includes nucleus basalis (of Meynert) and septal nuclei b. Cholinergic neurons project diffusely to cerebral cortex
4. Cerebral cortex: diffuse localization
C. Anatomy of Attention 1. Inferior posterior parietal cortex and the primary and
association sensory cortices are important for perception of a novel stimulus and initiation of a response to the stimulus a. Superior colliculus, pulvinar, and parietal lobe have
extensive connections with the frontal eye fields: all important for perception of a novel visual stimulus
b. Sensory cortices selectively inhibit the thalamic nucleus reticularis and reduce the inhibitory effect of this nucleus on other thalamic nuclei, promoting thalamic relay of sensory input
2. Prefrontal cortex (especially mesial frontal area), frontal eye fields, and anterior cingulate cortex are responsible for executing spatial attention and selectively focusing attention on the novel stimulus (while inhibiting attention to the other, less important stimuli in the environment) as well as nonspatial attention a. Lesion can cause nonspatial inattention: motor and
verbal impersistence, perseveration, and akinetic mutism with severe involvement of the mesial frontal lobes bilaterally or a diffuse cortical process
3. Striatum (especially caudate) a. Projects to prefrontal areas and is an important modulator
of prefrontal function b. Lesion of caudate or frontostriatal projections: apathy
and disinhibition (unilateral or bilateral) 4. Primary and association sensory cortices 5. Thalamus and ascending reticular activating system
promote arousal and are important in maintenance of consciousness
D. Dysfunction of Attention 1. Diffuse inattention
a. Acute confusional state (i.e., delirium) b. Chronic dysfunction of attention and memory as a con-
fabulatory state (e.g., Korsakoff’s syndrome) c. Depression or other psychiatric disease d. Subcortical dementia-global inattention associated with
a “frontal-dysexecutive syndrome” and possibly other frontal lobe features: may be caused by involvement of striatofrontal projections and other subcortical pathways as in normal-pressure hydrocephalus, Binswanger’s disease, or CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)
2. Unilateral inattention a. Unilateral signs: spatial sensory neglect (most sensitive
exam is with bilateral simultaneous stimuli), hemiakinesia (motor neglect), anosognosia (unawareness of the deficit), allesthesia (stimulation of the affected side of the body is interpreted as stimulation of the unaffected side)
b. May be difficult to determine when there is severe deficit of the primary sensory modality 1) Visual inattention may be difficult to determine if
patient has a dense hemianopia 2) Examining the patient after directing the eyes toward
the unaffected side would help to distinguish hemispatial inattention from hemianopsia (deficit persists regardless of the direction of gaze)
c. Right hemispheric lesions usually cause contralateral spatial neglect (not usually seen with left hemispheric lesions) 1) Right hemisphere (likely the inferior parietal area) is
responsible for attention for both sides of the body, and left hemisphere only for the right (contralateral) side of the body
2) Anosognosia: patient is unaware of the acquired deficits (e.g., hemiparesis and nonmotor perceptual and cognitive dysfunction), most commonly seen with acquired right hemisphere lesions
3) Anosodiaphoria: patient is indifferent to his/her condition despite the recognition of hemiparesis or hemisensory deficits, often with right hemisphere lesions
4) Right hemisphere lesions may also be associated with the following: a) Aprosody, i.e., reduced “emotional flow” and
misperception of emotional tone in one’s speech (right hemisphere involvement, especially right parietotemporal region)
b) Misperception of facial expressions (right parietooccipital lesion)
c) Topographagnosia or topographic disorientation, i.e., impaired spatial orientation and navigation in the environment; involvement of right posterior parahippocampal region, infracalcarine cortex of either hemisphere, or less commonly, right parietal lesions
d. Hemiakinesia or motor neglect: reduction of exploratory motor behavior to the neglected side, primarily a result of sensory inattention and feedback
A. Definitions 1. Learning
a. Acquisition of new knowledge and experience and alteration of behavior as a result of the experience
b. In its simplest form, it represents change in response over time to repeated exposure to the same stimulus
2. Memory: storage and retrieval mechanism for learned knowledge
3. Plasticity a. Learned behavior can be modified with modulation and
alteration of adaptable “plastic” neuronal pathways b. Alterations in neuronal excitability and synaptic connec-
tivity are physiologic correlates of plasticity and are responsible for learning and memory
4. Encoding: acquisition or learning of new information 5. Retrieval: recall of knowledge previously encoded and
stored as long-term memory 6. Modalities of memory
a. Explicit (declarative) memory 1) Knowledge that requires conscious recall and acquisi-
tion: example is semantic memory, which is factual knowledge and meaning of people, places, and things; requires fast acquisition and conscious recall (e.g., geography)
2) First step for acquisition of knowledge (encoding) involves perception of sensory input, executed by association cortices and their connections, e.g., visual association cortices are involved in “understanding” and encoding of specific aspects of a particular visual stimulus before it is stored
3) Acquisition of explicit knowledge (encoding) is executed by mesial temporal lobe and surrounding structures, including parahippocampal and entorhinal cortices through the excitatory loop of Papez
4) Long-term storage of explicit memory: distributed network involving association cortices (after encoding by mesial temporal structures)
5) Different aspects of a particular experience are stored in different brain regions, and memory for a certain experience is eventually stored in a distributed network
6) Disease of a particular brain region causes loss of previously acquired knowledge in that brain region and loss of ability to acquire new knowledge in that brain region
7) Types of explicit knowledge a) Semantic
i) Knowledge of facts, objects, and abstract concepts unrelated to events (e.g., geography)
ii) Semantic memory requires inferotemporal association areas and other regions outside mesial temporal lobe
iii) Semantic memory loss usually accompanies episodic memory loss
iv) Isolated semantic memory loss may be seen in a form of frontotemporal dementia (semantic dementia) and can also be seen in Alzheimer’s disease in conjunction with memory and other deficits
b) Episodic i) Knowledge of past events that have been
encoded and stored with certain associations established in particular time and place
ii) Short term: limited capacity, requires repetitive recall
Types of Memory Explicit (declarative) memory: knowledge that requires conscious recall and acquisition; requires fast acquisition and conscious recall
Semantic memory Episodic memory
Implicit (nondeclarative) memory: knowledge that does not require conscious recall; acquisition is generally slow
Procedural memory Priming
Verbal vs. nonverbal memory
Anterograde vs. retrograde memory
Short-term vs. long-term memory
Working memory
iii) Long term: long-lasting or permanent, relatively more resistant to dementing illness and cerebral insult than short-term memory
iv) Anterograde memory: knowledge for experiences that occur after a certain event (anterograde memory loss refers to inability to acquire new information after a particular insult)
v) Retrograde memory: previously acquired information
b. Implicit (nondeclarative) memory 1) Knowledge that does not require conscious recall,
acquisition is generally slow 2) Types of implicit knowledge
a) Procedural memory i) Knowledge for performing a motor task is
slowly acquired (learned) by repeatedly performing the same task
ii) Acquisition is slow and incremental, the knowledge is resistant to forgetfulness by degenerative conditions
iii) Motor skill learning likely occurs with the participation of the pyramidal, extrapyramidal, and cerebellar motor systems and their cortical projections
iv) Cortical pathways important for skilled motor movements: motor cortex, premotor cortex, supplementary motor cortex, the parietal lobe (lesion of these pathways may produce apraxis [see below])
b) Priming: perceptual (nonmotor) priming is linked to modality-specific neocortices
7. Division of memory based on the type of knowledge stored a. Verbal
1) Generally stored in left hemisphere (dominant hemisphere)
2) Anterograde amnesia for verbal memory (i.e., defective acquisition of verbal information) may be seen with left temporal lobe injury
b. Nonverbal 1) Generally stored in right hemisphere 2) Anterograde amnesia for visual memory may be seen
with right temporal lobe injury; patient may have difficulty recognizing faces, objects, etc.
