L13 - Development and Plasticity

Prenatal formation of the brain

• Formation of CNS occurs during prenatal development

Brain structure development steps:

• Cell division

  • Where system makes all cells needed for brain

  • First step in wiring cerebral cortex is generating neurons

    • Stem cells in CNS divide into two daughter cells

    • When newly divided cells migrate and take up position in cortex, the stem cell remains and undergoes more divisions until all cortical neurons have been generated

• Cell migration

  • Newly formed cells make way to where they’ll reside in brain

    • Migrate along temporary ‘scaffolding’ (thin fibres radiating to surface of brain) made by glial cells

  • Cortical layers get formed from inside out (layer 1→outer layer→outer layer etc)

    • New cells keep making way past the already formed layers until there’s 6 layers total

• Cell differentiation

  • Newly divided cells take on appearance and characteristics of neurons or glial cells

• Neurons extend their axons to appropriate targets in order to form inter-neuronal connections

Postnatal plasticity

• Brain development continues after birth but plasticity declines with age

• Neural plasticity: ability of NS to change

  • Adult brain is comparatively rigid to newborn but still undergoes plasticity

• Connections are modified by sensory experience

  • Basic brain circuitry in place as birth but fine-tuning is driven by neuronal activity

    • E.g. The level of overlap in neural projections from eyes at birth vs months of sensory experience

    • Cells that fire together wire together

• Formation of ocular dominance columns in V1:

  • At birth, LGN inputs repping both eyes are intermingled within V1 (projections overlapping from each eye)

  • Over course of early postnatal development, the eyes’ inputs segregate into ocular dominance columns

    • Alternating stripes of V1 neurons that preferentially respond to visual input from either left or right eye

    • This fine-tuning of wiring is driven (in part) by sensory experience

• Von Melchner et al. (2000): rewiring visual input to auditory system in newborn ferrets

  • Retinal ganglion cells in left hemisphere (originally bound for SC) are redirected to medial geniculate nucleus and SC and IC were removed

    • Right hemisphere intact still

    • A1 now receives info from eyes

    • Looking at response properties of A1 if incoming info is visual

    • Normally IC neurons send axons to MGN and they send theirs to A1

  • Result: after raised to adulthood, single cell recording showed neurons in A1 in rewired/left hemisphere behaved like visual neurons in response to visual stimuli (had retinotopic organisation)

    • Shows plasticity as A1 developed a retinotopic map rather than normal tonotopic

  • Also lesioned LGN so visual cortex couldn’t just support visual behaviour (to isolate effects of A1 supporting visual behaviour)

    • Animals behaved as if they could see

  • Wouldn’t work in adult ferrets bc lack of sufficient plasticity

• Gothe et al. (2002): stimulating visual cortex in human adults with natural impaired vision

  • Some residual vision, very poor residual vision, no residual vision

  • Used TMS over visual cortex and measured self-reported phosphene experience

    • Effect of activating visual cortex differed by severity of visual impairment - lower % with worse vision (esp those without previous visual experience)

      • The 2 participants who had experienced phosphenes without residual vision were not congenitally blind (from birth)

      • One congenitally blind patient reported a localised warmth sensation in contralateral half of his grasping space when occipital cortex was stimulated

        • Suggests it has something to do with somatosensation

• Lambert, Sampaio, Mauss & Scheiber (2004): mental imagery in sighted and congenitally blind adults

  • Which brain structure activated during mental imagery in sighted vs congenitally blind adults?

  • Used fMRI

    • Brain activity during passive listening to abstract words was subtracted from brain activity in mental imagery task

  • Both congenitally blind, and sighted participants had activation of visual cortex associated with mental image production

    • Even though seeing occipital lobe activation, doesn’t mean that response properties are similar to those with prior visual experience

    • If congenital - brain develops in different ways bc isn’t getting that sensory input that drives a lot of development of response properties and fine-tuning of wiring

• Recanzone et al. (1993): training and plasticity in A1 for monkeys

  • Training monkeys to discriminate specific tone frequencies enlarges associated brain regions

    • Demonstrates functional plasticity in A1

• Karni et al. (1998): training and plasticity in M1 for humans

  • Trian finger taps with non-dom hand in specific sequence daily for many weeks

  • Using fMRI, measured activity-related blood flow changes in M1 for practiced sequence vs performing a new one they hadn’t trained for

    • More brain volume recruited to support trained skill (more activation) in contralateral M1 after only 3 weeks of training

    • After 8 weeks: greater blood flow changes persisted even without training

      • Shows retention

  • Conclusion: in human adult brain, training can induce rapid brain activity changes that show the NS’s plastic ability to acquire and retain new info and skills

• Erickson et al. (2011): declining plasticity and more atrophy in aging brain

  • Creates memory function decline - connected to age-related hippocampus size reductions

  • Research in older adults shows aerobic exercise can increase hippocampus size (decreases for stretching)

    • Also improved accuracy of spatial memory

      • Shows not just structural brain improvements - also functional/behavioural

Key terms

Subcortical Visual and Motor Structures

Superior Colliculus (SC)

• Anatomical Definition and Location:

  • Paired subcortical structure forming the upper swellings of the midbrain tectum, located directly below the thalamus on the dorsal brainstem.

  • Possesses a laminar (layered) anatomical architecture separated into superficial and deep layers.

• Sensory and Motor Mapping Across Layers:

  • Superficial Layers: Receive direct visual projections from retinal ganglion cells ($\sim 10\%$ of optic tract axons via the retinotectal pathway). Contain an orderly retinotopic map representing the contralateral visual hemifield (Goldberg & Wurtz, 1972).

  • Cortical Magnification: The retinotopic map in the superficial SC is structurally distorted, allocating an expanded proportion of neural tissue to processing central visual space.

  • Deeper Layers: House sensorimotor and pure motor neurons possessing broadly tuned movement fields rather than receptive fields; fire bursts of action potentials prior to saccadic eye movements into the contralateral hemifield (Wurtz & Goldberg, 1972).

  • Topographical Alignment: The superficial visual retinotopic map lines up directly over the deep motor map (Wurtz & Munoz, 1972). The rostral SC represents central fixation and small-amplitude saccades, whereas the caudal SC codes for large-amplitude saccades.

• Oculomotor Reflexes and Fixation Control:

  • Mediates rapid, primitive reflexive (exogenous) saccades to peripheral visual transients.

  • Fixation Cells: Located in the rostral SC; fire tonically during active visual foveation and decrease firing prior to saccades (Munoz & Wurtz, 1993).

  • Mutual Inhibition: Collicular fixation cells actively inhibit saccade-generating movement cells, establishing an opponent process underlying the fixation reflex and the fixation offset effect.

• Cortical Regulation and Lesion Dynamics:

  • Unilateral SC lesions in humans selectively impair and delay reflexive saccade latencies to contralesional targets while sparing ipsilesional saccades (Pierrot-Deseilligny et al., 1991).

  • Sprague Effect: Cortical blindness from unilateral visual cortex ablation in cats halts orienting toward the contralateral hemifield; orienting is restored by ablating the contralesional SC or severing intercollicular inhibitory fibers, disinhibiting the ipsilesional SC.

  • Top-Down FEF Modulation: The Frontal Eye Fields (FEF) exert tonic inhibitory control over the ipsilesional SC. Unilateral FEF damage releases the ipsilesional SC from inhibition, leading to hyperactive, erroneous reflexive saccades into the contralesional visual field during anti-saccade tasks (Machado et al., 2004).

• Multisensory Integration and Blindsight:

  • Receives ascending inputs from the inferior colliculus, enabling the integration of auditory and visual spatial maps.

  • Underpins residual visual function (blindsight) in patients with primary visual cortex (V1) lesions, driving unconscious target localization (Weiskrantz, 1986) and distractor interference (Rafal, 1990).

Inferior Colliculus (IC)

• Anatomical Definition and Location:

  • Paired auditory relay nuclei located on the dorsal midbrain immediately caudal (inferior) to the superior colliculi, overlying the cerebral aqueduct.

• Auditory Processing and Pathway:

  • Receives ascending acoustic projections bilaterally from the cochlear nuclei of the brainstem.

  • Synapses directly onto principal projection neurons within the Medial Geniculate Nucleus (MGN) of the thalamus, which in turn project to primary auditory cortex (A1).

  • outer → middle → inner ear → brainstem → IC → MGN → A1

• Multisensory Connections and Neuroplasticity:

  • Projects axons to the superior colliculus to provide auditory spatial coordinates that align with the collicular retinotopic map for multimodal orienting.

  • In neonatal cross-modal rewiring studies (von Melchner et al., 2000), surgical ablation of the IC and SC enabled retinal axons to route aberrantly into the MGN, driving auditory cortex to adopt visual response properties.

Thalamic Nuclei

Lateral Geniculate Nucleus (LGN)

• Anatomical Definition and Function:

  • Thalamic sensory relay nucleus dedicated to vision, situated in each cerebral hemisphere at the top of the brainstem.

  • Major subcortical target of the cortical visual pathway (retinogeniculostriate pathway), receiving $\sim 90\%$ of all retinal ganglion cell axons via the optic tract.

• Topographical and Functional Organization:

  • Contains an orderly retinotopic map representing the contralateral visual hemifield (right LGN processes left hemifield; left LGN processes right hemifield).

  • Transmits visual input directly to primary visual cortex (V1 / striate cortex) bordering the calcarine fissure.

• Developmental Segregation:

  • Inputs from the two eyes terminate in overlapping zones within V1 at birth before activity-dependent competition drives them into distinct ocular dominance columns.

Medial Geniculate Nucleus (MGN)

• Anatomical Definition and Function:

  • Thalamic sensory relay nucleus dedicated to audition, receiving ascending acoustic signals from the inferior colliculi.

  • Projects tonotopically organized axonal radiations to primary auditory cortex (A1 / Heschl’s gyrus) buried within the lateral sulcus.

• Role in Plasticity Models:

  • Served as the anatomical target in neonatal ferret rewiring experiments (von Melchner et al., 2000), wherein surgically diverted retinal ganglion cell axons formed functional synapses, driving A1 to express retinotopic maps and visual tuning.

Cortical Sensory Areas and Visual Streams

Primary Visual Cortex (V1 / Striate Cortex / Brodmann Area 17)

• Anatomical Definition and Location:

  • First cortical stage of visual processing, situated in the medial occipital lobe and buried within the banks of the calcarine fissure.

• Neural Architecture and Maps:

  • Contains a complete retinotopic map of the contralateral visual hemifield established via point-to-point projections from the LGN (Tootell et al., 1982).

  • High population coding: functional imaging demonstrates that representing a single visual image recruits at least $200\text{ million}$ visual cortex neurons (Levy, Hasson, & Malach, 2004).

• Clinical Lesions and Residual Function:

  • Unilateral destruction causes complete contralesional homonymous hemianopia (cortical blindness in the opposite visual field), detectable via perimetry mapping.

    • Perimetry testing: Tests the visual field and maps blind spots (scotomas) where a patient is non-responsive by having them report whether they saw a light stimulus; used to detect visual field loss such as contralesional hemianopia following unilateral V1 damage.

    • Also maps scotomas/blind spots

      • Scotomas: Blind spots within the visual field where a patient is non-responsive to light stimuli, which can be mapped using perimetry testing.

    • Cortical blindness spares the subcortical retinotectal pathway, allowing unconscious visual orienting and blindsight (Weiskrantz, 1986; Rafal, 1990).

• Cortical Excitability and Plasticity:

  • Phosphenes: Transcranial magnetic stimulation (TMS) delivered over the occipital pole evokes perceived flashes of light (phosphenes). The phosphene threshold indicates visual cortical excitability, which is significantly lowered in heavy ecstasy users and chronic hallucinators (Oliveri & Calvo, 2003).

  • Sensory Experience Deprivation: TMS evokes phosphenes in late-blind adults but fails to evoke visual percepts in congenitally blind individuals, who instead report somatic tactile or warmth sensations (Gothe et al., 2002).

  • Mental Imagery: Functional neuroimaging reveals robust visual cortex activation during mental imagery tasks in both sighted and congenitally blind adults (Lambert et al., 2004).

• EOG (Electrooculography): Measures eye movement by picking up the polarity difference from the front to the back of the eye.

• EMG (Electromyography): Measures muscle electrical activity, such as recording from the lateral rectus eye muscle which moves the eye toward the periphery along the horizontal axis.

Extrastriate Cortex and Dual Visual Streams

• Extrastriate Visual Areas (V2, V3, V4, V5/MT):

  • Cortical visual processing regions situated beyond V1 that maintain topographical representations of the contralateral hemifield.

  • Topographical Discontinuity: Spatial maps do not transition smoothly across boundaries; instead, retinotopic layouts mirror or flip at the anatomical border of each successive visual area.

• Dorsal Stream (“Where” / Spatial Pathway):

  • Connects V1→V2→V3→MT/V5, and posterior parietal cortex; specialized for processing spatial location, motion, and visual guidance of motor action.

  • Area MT / V5: Located in extrastriate cortex; specialized for decoding the direction and speed of visual motion (Maunsell & Van Essen, 1983; Zeki et al., 1991).

• Ventral Stream (“What” / Object Identification Pathway):

  • Connects V1→V2→V4→inferotemporal (IT) cortex; specialized for high-resolution form, feature extraction, and object identity.

  • Area V4: Extrastriate cortical region highly selective for colour and geometric form. PET subtraction studies isolating colour processing from greyscale stimulation identified focal V4 activation (Zeki et al., 1991).

Primary Auditory Cortex (A1 / Heschl’s Gyrus)

• Anatomical Definition and Location:

  • First cortical region to receive and process acoustic information; located on the superior temporal gyrus and buried within the lateral sulcus.

• Tonotopic Organization:

  • Neurons are organized along a frequency gradient (tonotopic map) mirroring the cochlea, where adjoining clusters of cells respond maximally to characteristic sound frequencies (Bear et al., 1996).

    • Base=high frequencies, apex=low frequencies

• Bilateral Projection Architecture:

  • Receives auditory input derived from both ears due to bilateral fiber decussation in the brainstem. Consequently, unilateral lesion of A1 does not cause cortical deafness.

• Adult Functional Plasticity:

  • Extended training on pitch discrimination tasks expands the corresponding frequency representation across A1 in non-human primates (Recanzone et al., 1993).

Frontal Oculomotor and Executive Regions

Frontal Eye Fields (FEF) and Superior Prefrontal Cortex (SPFC)

• Anatomical Definition and Location:

  • Cortical oculomotor region situated in the frontal lobe at the intersection of the superior frontal sulcus and the precentral sulcus.

• Functional Role in Saccadic Control:

  • Generates voluntary (endogenous) saccades based on internal goals, spatial memory, and symbolic instructions.

  • Disruption of the SPFC/FEF via TMS selectively delays the initiation of voluntary, arrow-cued saccades into the contralateral visual field without altering reflexive saccades (Ro et al., 1997).

  • Patients with unilateral structural lesions of the FEF exhibit marked latency increases for voluntary saccades directed toward the contralesional hemifield (Henik et al., 1994).

• Top-Down Inhibitory Regulation:

  • Provides essential top-down inhibition over the primitive reflex circuitry of the superior colliculus.

  • Lesions of the FEF produce marked failure to suppress reflexive glances during anti-saccade tasks, causing disinhibited contralesional saccadic errors (Machado et al., 2004).

Peripheral Sensory and Neural Receptors

Auditory Apparatus and Pathways

• Outer Ear:

  • Pinna: Cartilage-supported skin folds that funnel acoustic pressure waves into the external auditory canal. Its contours reflect sounds to generate spectral cues necessary for vertical elevation sound localization.

  • Auditory Canal: Conducts sound pressure waves from the external environment to the tympanic membrane.

• Middle Ear:

  • Tympanic Membrane (Eardrum): Vibrates inward and outward in response to high- and low-pressure acoustic wavefronts.

  • Ossicles (Malleus, Incus, Stapes): Mechanical lever chain transferring tympanic vibrations onto the fluid-filled oval window of the inner ear.

• Inner Ear and Neural Transduction:

  • Cochlea: Fluid-filled, coiled structure containing the organ of Corti. Mechanical fluid waves deflect hair cell cilia, transducing mechanical displacement into electrical receptor potentials.

  • Spiral Ganglion Cells (SGCs): Primary sensory neurons tuned to discrete characteristic frequencies, establishing a peripheral tonotopic map. Their axons form the auditory nerve.

  • Vestibulocochlear Nerve: Cranial nerve transmitting acoustic signals from SGCs and balance signals from vestibular organs to the cochlear nuclei at the pontomedullary junction.

  • Sound Localization Mechanisms: Localizes sound horizontally via interaural time differences (arrival delays between ears) and vertically via pinna spectral filtering.

  • Cochlear Implants: Surgically implanted neuroprosthetics stimulating SGCs directly using an electrode array ($\sim 24$ electrodes) to bypass damaged hair cells.

    • Stimulates hair cells rather than amplifying sound like ordinary hearing aids

• Tinnitus

  • Persistent phantom noises in absence of any sound stimulus

  • Typically caused by disease processes affecting the cochlea or auditory nerve or spontaneous activity

  • Transient tinnitus: temporary phantom noises after loud exposure (e.g. Concert). Prolonged instances like this can make it worse/permanent

Visual Apparatus and Retinal Architecture

• Gross Anatomy:

  • Cornea and Lens: Primary refractive elements focusing incident light rays onto the posterior retina.

  • Pupil and Iris: Aperture and muscular diaphragm regulating internal retinal illumination.

  • Sclera: Tough, protective fibrous outer white coat continuous with the transparent cornea.

  • Macula and Fovea: Central retinal zones specialized for high-acuity central vision. In the foveal pit, inner retinal layers (bipolar and ganglion cells) are displaced laterally, providing an unhindered optical path directly to packed foveal cones.

• Photoreceptors:

  • Rods: Highly sensitive ($\sim 1000\times$ more sensitive than cones), specialized for scotopic (dim-light) peripheral vision, containing a single photopigment.

  • Cones: Specialized for photopic (bright-light) central vision and high visual acuity; categorized into three types based on photopigments absorbing blue, green, and red wavelengths.

• Retinal Neural Circuitry:

  • Laminar sequence: Photoreceptors $\rightarrow$ Horizontal cells $\rightarrow$ Bipolar cells $\rightarrow$ Amacrine cells $\rightarrow$ Retinal Ganglion Cells (RGCs).

  • Blind Spot (Optic Disc): Retinal region lacking photoreceptors where unmyelinated RGC axons converge to form the optic nerve; sits $\sim 15^\circ$ into the nasal hemiretina (temporal visual field).

• Visual Fields, Decussation, and Tract Lesions:

  • Nasal Hemiretinae: Axons decussate (cross the midline) through the optic chiasm.

  • Temporal Hemiretinae: Axons remain ipsilateral, proceeding uncrossed.

  • Lesion Patterns:

    • Cutting an optic nerve abolishes monocular vision.

    • Transecting the optic chiasm abolishes decussating nasal hemiretinal fibers, producing bitemporal hemianopia (tunnel vision).

    • Severing an optic tract strips the contralateral visual hemifield entirely (contralateral homonymous hemianopia).

Cellular Neurobiology and Glia

Glial Cell Classifications

• Astrocytes:

  • Maintain the blood-brain barrier (BBB) via perivascular end-feet, protecting neural tissue from blood-borne toxins.

    • BBB: between neuronal tissue and blood and protects CNS from certain molecules in the bloodstream

  • Facilitate the glymphatic system, flushing cerebrospinal fluid through interstitial brain tissue during sleep to clear metabolic waste and debris.

    • Glymphatic system: waste clearance system in CNS

      • Especially during sleep (linked to brain health)

• Oligodendrocytes:

  • Synthesize lipid-rich myelin sheaths in the central nervous system by wrapping membrane layers around multiple adjacent axons.

  • Target of autoimmune demyelination in multiple sclerosis (MS), which degrades saltatory nerve impulse conduction.

• Microglia:

  • Primary resident immune phagocytes of the CNS; migrate to injury sites to engulf and eliminate decaying cellular debris and degenerating brain cells.

Neuron Structure and Synaptic Transmission

• Structural Domains:

  • Dendrites: Treelike processes receiving chemical inputs via post-synaptic receptor sites.

  • Soma: Cell body containing metabolic machinery and the cell nucleus.

  • Axon: Transmits all-or-none action potentials away from the cell body toward distant targets; often diverges into axon collaterals.

  • Axon Terminals: Presynaptic swellings housing synaptic vesicles containing chemical neurotransmitters.

• Synaptic Transmission:

  • Depolarization at the presynaptic terminal mobilizes synaptic vesicles to release neurotransmitters into the synaptic cleft.

  • Neurotransmitters bind to post-synaptic receptors, converting chemical signals back into electrical graded potentials capable of initiating postsynaptic action potentials.

Systems Neurobiology and Visual Behaviour

Cortical vs. Subcortical Visual Systems

• Retinogeniculostriate Pathway (Cortical System):

  • Retina $\rightarrow$ LGN $\rightarrow$ V1; encompasses $\sim 90\%$ of visual projections.

  • Phylogenetically newer; enables conscious visual perception, fine spatial discrimination, and detailed feature analysis (Schneider, 1969).

• Retinotectal Pathway (Subcortical System):

  • Retina $\rightarrow$ Superior Colliculus; encompasses $\sim 10\%$ of visual projections.

  • Phylogenetically older; coordinates visual spatial localization and rapid reflexive orienting responses toward peripheral stimuli (Schneider, 1969).

• Blindsight Capabilities:

  • Cortically blind patients with damaged V1 retain unconscious visually guided localization (Weiskrantz, 1986).

  • Distractor stimuli flashed within the blind hemifield delay saccadic latencies toward intact-field targets, proving that the subcortical retinotectal pathway actively processes inputs without conscious awareness (Rafal, 1990).

Oculomotor Control and Reflex Modulation

• Exogenous vs. Endogenous Saccades:

  • Exogenous (Reflexive) Saccades: Rapid, automatic eye movements triggered by sudden external visual transients; driven by the subcortical retinotectal pathway and brainstem burst generators.

  • Endogenous (Voluntary) Saccades: Slower, internally driven, goal-directed eye movements initiated by cortical networks involving the FEF and SPFC.

• Fixation Offset Effect (FOE):

  • Has fixation overlap and fixation offset trials

  • Saccadic latency to foveate an exogenous target is delayed when the central fixation point remains illuminated (overlap trial) compared to when it extinguishes (offset trial).

  • Underpinned by reciprocal mutual inhibition between collicular fixation cells and movement cells (Munoz & Wurtz, 1993).

  • Infants aged $1.5\text{--}2\text{ months}$ show pronounced overlap delays ("sticky fixation") due to immature cortical suppression over collicular fixation reflexes (Hood & Atkinson, 1993).

• Anti-Saccade Task:

  • Requires looking in the exact mirror-opposite direction of a sudden peripheral onset, demanding active inhibition of a reflexive saccade followed by generating a voluntary saccade.

  • Developmental Progression: Direction errors and reaction times drop markedly between ages 5 and 15 alongside prefrontal cortical maturation (Fischer et al., 1997; Munoz et al., 1998).

  • Frontal Pathology and Aging: Adult FEF lesions trigger severe disinhibition of reflexive glances toward contralesional visual targets (Machado et al., 2004). Healthy aging causes cortical atrophy, re-emerging higher anti-saccade error rates (Sweeney et al., 2001).

Visual Attention Paradigms

Attentional Mechanisms and Paradigms

• Overt vs. Covert Attentional Orienting:

  • Overt Orienting: Shifting visual gaze and attention concurrently to foveate a target.

  • Covert Orienting: Shifting the locus of spatial attention while maintaining static central fixation. Covertly attending to a visual hemifield selectively amplifies sensory Event-Related Potential (ERP) amplitudes across contralateral occipital cortex.

• Exogenous vs. Endogenous Cueing:

  • Peripheral onset flashes trigger automatic exogenous attentional capture, whereas central directional cues (arrows) require endogenous voluntary deployment.

  • Short endogenous tasks: attenting to a stimulus facilitates responses and aids efficiency of visual search (shorter delay)

  • Long endogenous delay: disadvantages response speed and involves inhibition of return

• Inhibition of Return (IOR):

  • Reflexive attentional mechanism wherein responses to targets appearing at an exogenously cued location are delayed if a long interval (stimulus onset asynchrony) elapses after the cue.

  • Discourages visual re-inspection of previously attended coordinates to maximize visual search efficiency; robust IOR predicts superior driving safety (Bedard et al., 2006).

• Flanker Task and Distractibility:

  • Evaluates strategic executive control by measuring reaction time interference on incongruent trials (flanking distractors) versus congruent trials.

  • Healthy aging exacerbates flanker interference costs due to structural decline in prefrontal cortical control systems (Kouwenhoven & Machado, 2023; Grundler & Strasburger, 2020).

Neurodevelopment and Neural Plasticity

Stages of Neurodevelopment

• 1. Cell Division: Stem cells divide to generate daughter cells that differentiate into cortical neurons.

• 2. Cell Migration: Immature neuroblasts migrate radially from ventricular zones along radial glial scaffolding, constructing the cerebral cortex from the inside out (layer 6 up through layer 1).

• 3. Cell Differentiation: Migrated cells adopt mature phenotypic morphologies, elaborating dendrites and extending axons along chemical guidance pathways.

Forms of Neural Plasticity

• Ocular Dominance Column Formation:

  • Segregation of overlapping LGN afferents in V1 into alternating ocular dominance bands during early postnatal development, driven by sensory experience ("cells that fire together wire together").

• Cross-Modal Functional Reorganization:

  • Neonatal ferrets with retinal projections re-routed to the MGN develop functional retinotopic maps in A1 and demonstrate visually guided behavior (von Melchner et al., 2000).

• Skill Acquisition and Retention:

  • Motor sequence training expands primary motor cortex (M1) blood flow representations contralaterally on fMRI after 3 weeks, with expansions retained weeks post-training (Karni et al., 1998).

• Age-Related Neurogenesis and Hippocampal Reversal:

  • Age-related declines in neural plasticity and hippocampal volume correspond to memory loss. Aerobic exercise interventions reverse hippocampal atrophy and significantly improve spatial memory accuracy in older adults (Erickson et al., 2011).

Methodological Tools in Cognitive Neuroscience

Structural, Functional, and Perturbative Methodologies

• Brain Lesion Analysis:

  • Evaluates whether a damaged region of interest (ROI) is causally essential for a cognitive function by comparing lesioned patients against intact controls and control groups with damage outside the ROI.

• Electroencephalography (EEG) and Event-Related Potentials (ERP):

  • Scalp recordings measuring postsynaptic dendritic field potentials. Provides millisecond-level temporal resolution but weak spatial resolution.

  • Averaging across hundreds of trials cancels background noise to isolate event-related components defined by latency, amplitude, polarity, and scalp topography.

• Structural Neuroimaging (CT, MRI, DTI):

  • Computed Tomography (CT): Employs rotational X-ray attenuation to construct 3D horizontal structural density maps.

  • Magnetic Resonance Imaging (MRI): Aligns hydrogen protons in magnetic fields to generate high-resolution anatomical images across coronal, sagittal, and horizontal planes.

  • Diffusion Tensor Imaging (DTI): Tracks the directional diffusion of water along axonal bundles to map white matter tract trajectory and structural integrity.

• Functional Neuroimaging (PET, fMRI):

  • Positron Emission Tomography (PET): Tracks inhaled or injected radioactive metabolic tracers via cerebral blood flow; requires the subtraction method to isolate specific cognitive operations; limited by low temporal resolution.

  • Functional Magnetic Resonance Imaging (fMRI): Measures blood-oxygen-level-dependent (BOLD) metabolic signal changes in active brain regions; non-invasive with superior spatial resolution.

• Transcranial Magnetic Stimulation (TMS):

  • Delivers localized magnetic pulses across the scalp to induce transient excitation or virtual lesions in underlying cortical neurons, testing whether a cortical site is causally necessary for a behavioral operation.

• Single Cell Recording: Involves recording action potentials from an individual neuron to measure cell firing in response to different stimuli and define its receptive field, though it can accidentally detect activity

Directional Axes and Neuroanatomy

Axes, Planes, and Cavities

• Anatomical vs. Neuroanatomical Axes:

  • Body Axis: Superior (up), Inferior (down), Anterior (front), Posterior (back).

  • Neural Axis: Bends $90^\circ$ at the midbrain-diencephalon junction. Forebrain: Dorsal = superior, Ventral = inferior, Rostral = anterior, Caudal = posterior.

  • Brainstem and Spinal Cord: Dorsal = posterior, Ventral = anterior, Rostral = superior, Caudal = inferior.

• Slices of the Brain:

  • Horizontal (Axial): Slices parallel to the ground.

  • Coronal: Vertical section from ear to ear (resembling a crown or headband).

  • Sagittal: Vertical section dividing the brain from front to back along the longitudinal midline.

• Ventricular System:

  • Interconnected network of cavities filled with cerebrospinal fluid (CSF) providing mechanical cushioning and waste transport: Paired Lateral Ventricles $\rightarrow$ Midline IIIrd Ventricle (surrounding the thalami) $\rightarrow$ Cerebral Aqueduct (beneath colliculi) $\rightarrow$ IVth Ventricle (underlying cerebellum).

• Subcortical Forebrain Ganglia:

  • Basal Ganglia: Composed of the Caudate Nucleus, Putamen, and Globus Pallidus; critical for motor control and voluntary action.

  • Corpus Callosum: Massive C-shaped commissural white matter tract interconnecting the left and right cerebral hemispheres.

• Major Gyri:

  • Frontal Lobe: Superior, middle and inferior frontal gyrus

  • Temporal lobe: Superior, middle and inferior temporal gyrus

  • Parietal lobe: Superior and inferior parietal gyrus

  • Precentral and postcentral gyrus

• Major sulci:

  • Frontal: Superior and inferior frontal sulcus

  • Temporal: Superior and inferior temporal sulcus

  • Parietal: Intraparietal sulcus

  • Precentral, central and postcentral sulcus

  • Lateral sulcus (separates temporal, from frontal and parietal lobes)

• Cerebellum: hangs off brainstem by parietal lobe

• Brainstem:

  • Function: Contains structures essential for sustaining life (e.g., heartbeat, breathing), so stroke damage to the brainstem directly impairs these functions.

  • Divisions: Composed of the midbrain (housing the superior and inferior colliculi), the pons, and the medulla (which is continuous with the spinal cord).

Others:

• Olfactory Bulb: Different scents evoke different spatial patterns of neural activation in the olfactory bulb, which accounts for the ability to discriminate scents (Kauer et al., 1991).

Studies:

• Levy, Hasson, & Malach (2004): Scanned participants' visual cortex using fMRI while they viewed an image to determine the neural population required for visual representation, finding that at least 200 million neurons are involved in representing a single image.

• Bear et al. (1996): Mapped neural responses across primary auditory cortex (A1) to examine sound frequency representation, finding tonotopic maps where distinct neuronal populations are organized by their preferred tonal frequencies.

• Kauer et al. (1991): Recorded salamander olfactory bulb activity to investigate how scents are differentiated, finding that distinct scents evoke unique spatial patterns of neural activation that enable scent discrimination.

• Tootell et al. (1982): Administered a radioactive agent to monkeys viewing visual stimuli to map primary visual cortex organization, finding that metabolically active V1 neurons formed an orderly retinotopic map mirroring the external image.

• Oliveri & Calvo (2003): Applied TMS over the occipital cortex to test if chronic ecstasy use alters visual excitability, finding that ecstasy users and hallucinators had significantly lower phosphene thresholds, demonstrating heightened visual cortex excitability.

• Maunsell & Van Essen (1983): Performed single-cell recordings in macaque area MT (V5) using moving light bars to identify visual response properties, finding that MT neurons are selectively tuned to both the direction and speed of motion.

• Zeki et al. (1991): Used PET subtraction imaging during coloured and moving visual displays to isolate attribute-specific processing areas, finding that V4 selectively processes colour whereas V5 processes motion.

• Goldberg & Wurtz (1972): Recorded from superficial superior colliculus neurons in fixating monkeys to determine their sensory properties, finding an orderly, centrally magnified retinotopic map of the contralateral visual hemifield.

• Sprague (1966): Ablated the contralesional superior colliculus or severed intercollicular inhibitory fibers in cortically blind cats to restore visual orienting, finding that orienting toward the blind hemifield was restored by disinhibiting the ipsilesional superior colliculus.

• Schneider (1969): Tested rodents with visual cortex or superior colliculus lesions on seed localization and pattern discrimination tasks to dissociate visual pathways, finding that cortical vision is required for complex discrimination while subcortical vision mediates spatial orienting.

• Weiskrantz (1986): Instructed hemianopic patients to saccade toward unseen lights flashed in their blind hemifield upon hearing a tone to test for residual vision, finding accurate unconscious localization (blindsight) mediated by the subcortical retinotectal pathway.

• Rafal (1990): Measured hemianopic patients' saccadic reaction times to intact-field targets in the presence of unseen blind-field distractors to evaluate subcortical processing, finding that distractors significantly delayed saccades due to competing retinotectal activation.

• Wurtz & Goldberg (1972): Recorded deep superior colliculus neurons alongside eye-muscle activity in monkeys to characterize motor properties, finding broadly tuned movement fields that fire before saccades into the contralateral hemifield.

• Wurtz & Munoz (1972): Mapped both superficial and deep superior colliculus layers to evaluate sensorimotor integration, finding that superficial visual retinotopic maps spatially align directly over deeper motor maps.

• Pierrot-Deseilligny et al. (1991): Measured reflexive saccadic latencies in a patient with a unilateral superior colliculus lesion to determine collicular function in humans, finding that saccades toward contralesional targets were selectively delayed.

• Munoz & Wurtz (1993): Recorded rostral superior colliculus neurons during target foveation and offset to investigate fixation control, discovering fixation cells that fire during active foveation and mutually inhibit saccade cells.

• Ro et al. (1997): Applied TMS over the SPFC or SPL during voluntary and reflexive saccade tasks to isolate cortical oculomotor control, finding that SPFC disruption selectively delayed contralateral voluntary saccades.

• Henik et al. (1994): Measured arrow-cued saccadic latencies in patients with unilateral FEF lesions to determine the role of FEF in voluntary orienting, finding that voluntary saccades toward the contralesional hemifield were selectively delayed.

• Hood & Atkinson (1993): Tested 1.5-month-old infants on a fixation offset task to assess early oculomotor control, finding that infants exhibit pronounced fixation overlap delays due to immature cortical suppression of the subcortical fixation reflex.

• Fischer et al. (1997): Tested 9- to 15-year-olds on an anti-saccade task to track oculomotor maturation, finding a rapid decrease in direction errors and reaction times across this age range.

• Munoz et al. (1998): Examined anti-saccade performance in children aged 5 to 15 to assess frontal lobe development, finding that younger children made the most reflexive direction errors and that voluntary control improved markedly through age 15.

• Machado et al. (2004): Tested unilateral FEF lesion patients on an anti-saccade task to assess top-down oculomotor control, finding that FEF damage caused frequent erroneous reflexive saccades toward contralesional targets due to ipsilesional superior colliculus disinhibition.

• Sweeney et al. (2001): Compared anti-saccade performance between young and older adults to assess the effects of aging, finding that older adults made significantly more direction errors and had slower reaction times due to age-related cortical degeneration.

• Bedard et al. (2006): Evaluated the relationship between inhibition of return (IOR) and driving performance, finding that stronger IOR was significantly associated with better driving competence due to more efficient visual scanning.

• Grundler & Strasburger (2020): Investigated age-related driving declines to identify underlying attentional mechanisms, finding that increased distractibility and impaired attentional control directly account for poorer driving performance in older adults.

• Kouwenhoven & Machado (2023): Administered the Flanker task across age groups to evaluate strategic distractor resistance, finding that older adults experienced greater incongruent reaction time delays due to deteriorating cortical attentional mechanisms.

• Von Melchner et al. (2000): Surgically rerouted retinal inputs to the auditory thalamus (MGN) in newborn ferrets to test cross-modal plasticity, finding that primary auditory cortex developed retinotopic maps and successfully mediated visual behaviour.

• Gothe et al. (2002): Delivered TMS over the visual cortex of adults with varying degrees of visual impairment to evaluate cortical excitability, finding that late-blind participants experienced phosphenes while congenitally blind participants reported tactile warmth sensations rather than light.

• Lambert, Sampaio, Mauss & Scheiber (2004): Used fMRI during mental imagery tasks in sighted and congenitally blind adults to determine whether visual experience is required for imagery, finding robust visual cortex activation in both groups.

• Recanzone et al. (1993): Trained adult monkeys on tone discrimination tasks to investigate sensory plasticity, finding that discrimination training significantly expanded the tonotopic representations of the trained frequencies within primary auditory cortex.

• Karni et al. (1998): Used fMRI to monitor motor cortex activity during daily finger-tapping training in humans to evaluate skill acquisition, finding that training expanded contralateral M1 cortical recruitment that persisted for weeks.

• Erickson et al. (2011): Conducted a one-year randomized trial comparing aerobic exercise and stretching in older adults to test neuroplasticity in aging, finding that aerobic exercise increased hippocampal volume and significantly improved spatial memory.