Six-Layer Neocortex

• The neocortex (isocortex) comprises ~90% of the cerebral cortex and has a uniform 6-layer architecture
• The remaining cortex is allocortex — 3-layered (hippocampus = archicortex; olfactory cortex = paleocortex)

Granular vs. Agranular Cortex

Cortical Columns & Brodmann Areas

• Cortical columns — functional units that span all 6 layers; neurons in a column share similar receptive fields and response properties
• Best characterized in V1 (ocular dominance columns, orientation columns) and S1 (somatotopic columns)
• Brodmann areas — 52 cytoarchitecturally distinct regions mapped by Korbinian Brodmann (1909); many correspond to functional areas

• Largest lobe — ~1/3 of cortical surface
• Boundaries: anterior to central sulcus, superior to lateral (Sylvian) fissure
• Blood supply: ACA (medial surface) + MCA (lateral surface)

Primary Motor Cortex (M1) — Brodmann Area 4

• Location: precentral gyrus
• Function: execution of voluntary contralateral movements
• Contains Betz cells (giant pyramidal neurons, layer V) → origin of ~30% of corticospinal tract fibers
• Motor homunculus — somatotopic organization:
  • Medial surface: lower extremity (foot, leg, hip) → ACA territory
  • Lateral convexity: upper extremity, face, tongue → MCA territory
  • Hand and face have disproportionately large cortical representation (fine motor control)
• Output tracts: corticospinal (body) and corticobulbar (face/bulbar muscles)

Clinical Correlations

• Lesion → contralateral UMN weakness: spasticity, hyperreflexia, extensor plantar response
• ACA stroke → contralateral leg weakness (leg > arm)
• MCA stroke → contralateral face and arm weakness (face/arm > leg)
• Cortical lesion typically causes weakness that respects somatotopy, unlike internal capsule lesion (equal face/arm/leg)

Premotor & Supplementary Motor Areas — Brodmann Area 6

• Premotor cortex (lateral area 6):
  • Motor planning for externally guided movements
  • Integrates visual and sensory input with motor output
  • Lesion → difficulty with visually guided reaching
• Supplementary motor area (SMA, medial area 6):
  • Motor planning for internally generated sequences
  • Bimanual coordination, complex motor sequences
  • Lesion → alien hand syndrome (frontal variant), difficulty initiating movement, impaired sequencing
  • SMA seizures → bilateral tonic posturing, often mistaken for psychogenic events

Broca’s Area — Brodmann Areas 44 & 45

• Location: inferior frontal gyrus (pars opercularis = area 44; pars triangularis = area 45) — dominant hemisphere
• Function: speech production, motor programming of articulation, syntax/grammar
• Lesion → Broca’s aphasia:
  • Non-fluent, effortful, telegraphic speech
  • Comprehension intact (for simple commands; may struggle with complex syntax)
  • Repetition impaired
  • Naming impaired
  • Often accompanied by right hemiparesis (adjacent motor strip involvement)
  • Patient is typically aware and frustrated

Frontal Eye Fields (FEF) — Brodmann Area 8

• Location: posterior middle frontal gyrus
• Function: initiates voluntary conjugate saccades to the contralateral side

Prefrontal Cortex

Dorsolateral Prefrontal Cortex (DLPFC)

• Executive function: planning, organization, cognitive flexibility, working memory
• Lesion → dysexecutive syndrome: poor planning, perseveration, impaired working memory, poor abstraction
• Tested by: Wisconsin Card Sort Test, Trail Making B, digit span backward

Orbitofrontal Cortex (OFC)

• Social behavior, judgment, impulse control, emotional regulation
• Lesion → disinhibition syndrome: impulsivity, inappropriate social behavior, poor judgment, emotional lability
• Classic example: Phineas Gage (OFC damaged by iron rod)
• Also seen in: frontotemporal dementia (behavioral variant)

Medial Prefrontal / Anterior Cingulate Cortex

• Motivation, initiation of behavior, emotional processing
• Lesion → abulia (lack of will/initiative) or akinetic mutism (bilateral) — alert but no spontaneous speech or movement
• Bilateral ACA infarction is a classic cause

Frontal Lobe Clinical Syndromes

• Boundaries: central sulcus (anterior), parieto-occipital sulcus (posterior), lateral fissure (inferior)
• Blood supply: MCA (lateral) + ACA (medial parasagittal strip)

Primary Somatosensory Cortex (S1) — Brodmann Areas 3, 1, 2

• Location: postcentral gyrus
• Function: processing of contralateral somatosensory information
• Sensory homunculus: somatotopic map (medial = leg [ACA]; lateral = face/arm [MCA]); lips, tongue, and fingers have disproportionately large representation

Functional Sub-Areas of S1

Clinical — Cortical Sensory Loss

• Cortical sensory modalities (impaired with parietal lesions):
  • Stereognosis — object identification by touch (loss = astereognosis)
  • Graphesthesia — recognition of numbers/letters traced on skin (loss = agraphesthesia)
  • Two-point discrimination
  • Sensory extinction on double simultaneous stimulation
• Primary modalities preserved: pain, temperature, light touch, vibration (processed at thalamic level)
• This dissociation (cortical modalities lost, primary modalities intact) is the hallmark of a cortical vs. thalamic or peripheral lesion

Somatosensory Association Cortex — Brodmann Areas 5 & 7

• Location: superior parietal lobule
• Functions: sensorimotor integration, visuospatial processing, body schema, hand-eye coordination
• Lesion → optic ataxia (misreaching for visual targets), tactile agnosia, impaired spatial awareness

Supramarginal Gyrus — Brodmann Area 40

• Location: inferior parietal lobule (wraps around posterior end of Sylvian fissure)
• Functions: phonological processing, motor planning for skilled movements (praxis)
• Dominant hemisphere lesion → conduction aphasia, ideomotor apraxia
• Non-dominant hemisphere lesion → hemispatial neglect (often in conjunction with area 39/7)

Angular Gyrus — Brodmann Area 39

• Location: inferior parietal lobule (wraps around posterior end of STS)
• Functions: reading comprehension, writing, calculation, cross-modal semantic integration
• Dominant hemisphere lesion → Gerstmann syndrome

Gerstmann Syndrome

• Caused by lesion of the dominant (left) angular gyrus (area 39)
• Tetrad:
  • Acalculia — inability to perform calculations
  • Agraphia — inability to write
  • Finger agnosia — inability to identify individual fingers
  • Left-right disorientation
• Often accompanied by alexia with agraphia
• Classic board question: "patient cannot do math, cannot write, confuses fingers, and confuses left-right" → dominant angular gyrus

Hemispatial Neglect

• Definition: failure to attend to, report, or respond to stimuli on the side contralateral to a brain lesion, not explained by primary sensory/motor deficits
• Most common and severe with RIGHT (non-dominant) parietal lesions (inferior parietal lobule, temporoparietal junction)
• Also involves the right superior temporal gyrus, right frontal lobe, and subcortical structures

Parietal Lobe Syndromes Summary

• Boundaries: inferior to lateral (Sylvian) fissure, anterior to occipital lobe
• Blood supply: MCA (lateral surface), PCA (inferior/medial surface)

Primary Auditory Cortex — Brodmann Areas 41 & 42

• Location: Heschl’s gyrus (transverse temporal gyrus) — located on the superior surface of the temporal lobe, hidden within the Sylvian fissure
• Function: initial cortical processing of auditory information
• Tonotopic organization: different sound frequencies mapped along the gyrus
• Bilateral input: each ear projects to BOTH auditory cortices (unlike vision) → unilateral cortical lesion causes subtle hearing change, NOT deafness
• Unilateral lesion → difficulty with sound localization, impaired auditory discrimination on contralateral side
• Bilateral lesions → cortical deafness (rare)

Wernicke’s Area — Brodmann Area 22

• Location: posterior superior temporal gyrus (dominant hemisphere)
• Function: language comprehension (spoken and written)
• Lesion → Wernicke’s aphasia:
  • Fluent speech — normal rate, rhythm, prosody, but content is empty
  • Comprehension severely impaired
  • Repetition impaired
  • Paraphasic errors: phonemic ("spork" for "fork") and semantic ("knife" for "fork")
  • Neologisms (made-up words) and jargon
  • Patient is typically unaware of deficit (anosognosia for language)

Auditory Agnosia & Word Deafness

• Auditory agnosia: inability to recognize sounds despite intact hearing → bilateral auditory association cortex lesions
• Pure word deafness: cannot comprehend spoken language but can read, write, and speak normally → bilateral lesions isolating Wernicke’s area from auditory input, or unilateral left temporal lesion disconnecting both auditory cortices from Wernicke’s area
• Auditory verbal agnosia = pure word deafness (selective inability to comprehend spoken words)

Hippocampus & Memory

• Location: medial temporal lobe (floor of inferior horn of lateral ventricle)
• Function: memory consolidation (short-term → long-term); spatial navigation
• Memory types processed:
  • Declarative (explicit) memory: episodic (personal events) and semantic (facts)
  • NOT procedural memory (handled by basal ganglia/cerebellum)
• Bilateral hippocampal lesion → severe anterograde amnesia (cannot form new declarative memories)
• Unilateral lesion: dominant (left) → verbal memory deficit; non-dominant (right) → visuospatial memory deficit
• Classic cases: Patient H.M. (bilateral medial temporal lobectomy); herpes encephalitis (predilection for temporal lobes)

Amygdala

• Location: anterior medial temporal lobe, anterior to hippocampus
• Functions: emotional processing (especially fear conditioning), emotional memory, social cognition (reading facial expressions)
• Bilateral lesion → Klüver-Bucy syndrome:
  • Hyperorality — tendency to examine objects with mouth
  • Hypersexuality
  • Placidity — loss of fear/aggression
  • Visual agnosia (psychic blindness)
  • Hypermetamorphosis — compulsive exploration of environment
• Causes: herpes encephalitis, frontotemporal dementia, bilateral temporal lobectomy

Temporal Lobe Epilepsy (TLE)

• Most common focal epilepsy in adults
• Focus: mesial temporal structures (hippocampus, amygdala, parahippocampal gyrus)
• Common pathology: hippocampal sclerosis (mesial temporal sclerosis)
• Semiology:
  • Aura: rising epigastric sensation, déjà vu, jamais vu, fear/anxiety, olfactory/gustatory hallucinations, autonomic symptoms
  • Seizure: behavioral arrest → oroalimentary automatisms (lip smacking, chewing) → manual automatisms (fumbling, picking)
  • Post-ictal: confusion, amnesia, dysphasia (if dominant hemisphere)
• Interictal personality traits (Geschwind syndrome): hypergraphia, hyperreligiosity, altered sexuality, viscosity (circumstantial interpersonal style)

Visual Field Deficit — Meyer’s Loop

• Meyer’s loop carries inferior retinal fibers (representing the contralateral superior visual field) through the temporal lobe
• Temporal lobe lesion → contralateral superior quadrantanopia ("pie in the sky")
• Important in temporal lobe surgery planning (anterior temporal lobectomy for epilepsy)

• Boundaries: posterior to parieto-occipital sulcus
• Blood supply: primarily PCA; macular cortex has dual supply (PCA + MCA branch) → explains macular sparing

Primary Visual Cortex (V1) — Brodmann Area 17

• Location: banks of the calcarine sulcus (medial occipital surface)
• Also called striate cortex (due to line of Gennari — a prominent myelinated stripe in layer IV)
• Receives input from: lateral geniculate nucleus (LGN) of thalamus via optic radiation
• Retinotopic organization:
  • Upper visual field → below calcarine sulcus (lingual gyrus)
  • Lower visual field → above calcarine sulcus (cuneus)
  • Central/macular vision → posterior pole (large cortical area = cortical magnification)
  • Peripheral vision → anterior calcarine cortex

Visual Field Deficits by Lesion Location

Visual Association Areas (V2–V5)

• V2 (area 18) and V3 (area 19): secondary visual processing, border/contour detection
• Two processing streams diverge from V1:

Dorsal Stream — "Where / How" Pathway

• Route: V1 → V2 → V3 → V5/MT → posterior parietal cortex
• Function: spatial location, motion perception, visually guided action
• V5/MT = motion processing area
• Lesion of V5 (bilateral) → akinetopsia (motion blindness — world seen as series of frozen frames)
• Lesion of posterior parietal → optic ataxia (misreaching)

Ventral Stream — "What" Pathway

• Route: V1 → V2 → V4 → inferior temporal cortex
• Function: object recognition, face recognition, color processing
• V4 = color processing area
• Fusiform face area (ventral occipitotemporal) = face recognition
• Lesion of V4 (bilateral) → achromatopsia (loss of color perception; world appears gray)
• Lesion of fusiform face area (bilateral) → prosopagnosia
• Lesion of ventral stream → visual object agnosia (cannot identify objects by sight; can identify by touch)

Occipital Lobe Syndromes

Language Network Overview

• Broca’s area (areas 44/45) — speech production, motor programming
• Wernicke’s area (area 22) — language comprehension
• Arcuate fasciculus — white matter tract connecting Broca’s and Wernicke’s → critical for repetition
• Angular gyrus (area 39) — reading, writing, semantic integration
• Supramarginal gyrus (area 40) — phonological processing
• Supplementary motor area — speech initiation
• All are in the dominant hemisphere (left in ~95% of right-handers, ~70% of left-handers)

Aphasia Classification Table

Related Language and Disconnection Syndromes

Apraxia

• Definition: inability to perform learned, skilled motor acts despite intact motor strength, sensation, coordination, and comprehension
• Testing: ask patient to pantomime actions (e.g., "show me how you would use a comb") → if failed, demonstrate and ask to imitate → if failed, give actual object

Agnosia

• Definition: inability to recognize stimuli in a particular sensory modality despite intact primary sensory function
• The key is that the patient can perceive the stimulus but cannot assign meaning to it

Anosognosia

• Definition: unawareness or denial of a neurological deficit
• Most commonly associated with right parietal lobe lesions (right MCA stroke)
• Patient may deny hemiplegia, neglect the left side of the body, or deny blindness (Anton syndrome)
• Clinical significance: anosognosia impairs rehabilitation participation, predicts worse functional outcomes, and is distinct from psychiatric denial
• May be temporarily reversed by caloric vestibular stimulation (cold water in left ear)

Cerebral Dominance & Lateralization

• Language dominance by handedness:
  • Right-handers: ~96% left-dominant
  • Left-handers: ~70% left-dominant, ~15% right-dominant, ~15% bilateral
• Wada test (intracarotid amobarbital): used to determine hemispheric language dominance pre-operatively → largely replaced by fMRI

Key Syndromes by Lobe and Location