1) Etymology and First Uses

Agnosia originates from the Greek a- ("without") + gnosis ("knowledge"); Freud formalized the term in Zur Auffassung der Aphasien (1891). Apraxia comes from a- + praxis ("action/doing"); the label entered medical German in the late 19th century and was systematized by Liepmann in the early 1900s. These roots matter: agnosias deny access to meaning; apraxias sever intention from execution.

Origins of the Ideas: Lissauer’s 1890 analysis of "Seelenblindheit" proposed apperceptive vs associative visual agnosia - a split that still organizes clinicopathology. Liepmann then delineated ideomotor, ideational, and limb-kinetic apraxias, arguing for a left-hemisphere action network bridging posterior representations and frontal programs. Geschwind later reframed both families as "disconnection" syndromes.

2) From Single Lesions to Systems: The Modern Scaffold

The two-visual-streams account - ventral ("what") for perception/recognition and dorsal ("how/where") for action - explains why agnosias and apraxias often co-travel yet dissociate. This architecture generalizes beyond vision, with dorsal-ventral specializations replicated in language and praxis networks.

Large-scale intrinsic networks provide the disease-era context: the default-mode network (DMN) is preferentially involved in Alzheimer-spectrum disease, whereas the salience network (SN; anterior insula/dorsal ACC) is targeted in behavioral-variant frontotemporal dementia (bvFTD). These network targets predict symptom families - mnemonic/visuospatial agnosias in DMN diseases; socio-emotional and executive "apraxias of behavior" in SN diseases.

3) Agnosias: What Is Perceived vs What Is Known

Visual:

• Apperceptive vs Associative: Lissauer’s split remains useful at bedside and in imaging. Apperceptive cases fail early shape integration; associative cases copy but cannot link to stored meaning. 

• Subtypes: Prosopagnosia (faces), alexia without agraphia (word-specific), achromatopsia (color), akinetopsia (motion), simultanagnosia (scene integration) map to ventral or dorsal stream injury, often with ILF/IFOF disconnection. 

Auditory:

• Auditory Verbal Agnosia (Pure Word Deafness): Disproportionate failure to understand speech with relatively spared non-speech sound recognition; typically involves bilateral or dominant temporal pathways.

• Phonagnosia: Inability to recognize familiar voices; developmental and acquired forms underscore modality-specific person knowledge.

• Environmental Sound Agnosia: Selective difficulty with non-speech sounds, occasionally seen in AD.

Somatosensory:

• Tactile Agnosia/Astereognosis: Object recognition fails by touch despite intact primary sensation; classic with parietal lesions and dissociable from gross sensory loss.

Body/Space Knowledge:

• Autotopagnosia: Breakdown of the body schema - identifying or localizing body parts - classically with left parietal involvement.

4) Apraxias: Intention, Selection, Sequencing, and Control

Canonical Limb Apraxias:

• Ideomotor: Gesture imitation and pantomime are disordered despite understanding the command.

• Ideational: Multistep tool sequences collapse (order, object selection).

• Limb-Kinetic: Loss of deft, fractionated movements. Lesion-symptom mapping and meta-analyses implicate a left parietal-anchored praxis network with fronto-parietal and callosal connectors.

Constructional and Visuomotor Apraxias: Difficulty copying/drawing or assembling shapes links dorsal stream and right parietal hubs, and often co-occurs with neglect or Balint features.

Oculomotor and Optic Apraxias: In Balint’s syndrome, defective goal-directed gaze (oculomotor "apraxia") and reach (optic ataxia) emerge from bilateral occipitoparietal injury - prototypical "how" pathway failure.

Apraxia of Speech (AOS): In degenerative syndromes, a primary progressive AOS phenotype centers on left premotor/SMA and frontal insula networks; in nfvPPA, white-matter damage to speech production tracts is prominent.

White-Matter Foundations: Modern tractography shows praxis depends on a distributed graph; disruptions within SLF/ILF/IFOF predict gesture, tool-use, and naming deficits, integrating the disconnection tradition with network neuroscience.

5) Diagnosing by Mixtures: Mapping Syndromes onto Agnosia x Apraxia

Posterior Cortical Atrophy (PCA, Alzheimer Phenotype): Early visuoperceptual and spatial agnosias (simultanagnosia, alexia, object/form), constructional apraxia, and optic ataxia reflect dorsal-ventral posterior network compromise within the DMN/visuospatial systems.

Primary Progressive Aphasia (PPA):

• Semantic Variant (svPPA): An "associative agnosia" of concepts - especially for objects and faces - driven by anterior temporal network degeneration.

• Logopenic Variant (lvPPA): Phonologic working-memory breakdown (often AD-related) with posterior perisylvian/DMN involvement.

• Nonfluent/Agrammatic (nfvPPA): Motor-speech planning (AOS) and grammatical "praxis" impairments of sequencing, with dorsal frontal-insular network injury. Consensus criteria and imaging operationalize these subtype mixtures.

Behavioral-Variant Frontotemporal Dementia (bvFTD): Early salience-network degeneration and selective loss of frontoinsular von Economo neurons produce a social-executive praxis failure - goal selection, switching, and inhibition collapse - plus a social agnosia for others’ internal states. This explains disinhibition/apathy without primary amnesia or aphasia in early stages.

Why the Mixtures Recur: Healthy connectomes predict where degeneration spreads: disease-specific seeds erode connected networks ("network-based vulnerability"), yielding reproducible agnosia/apraxia cocktails rather than arbitrary symptom lists.

6) A Modality-Anchored Diagnostic Grammar (Bedside → Networks)

Visual Domain:

• Agnosia Axis: apperceptive (early shape integration; occipito-parietal/ventral entry) → associative (link to semantics; ventral temporal + ILF/IFOF).

• Apraxia Axis: constructional, optic ataxia, ocular "apraxia" (bilateral parietal).

Auditory Domain:

• Agnosia Axis: word deafness ↔ phonagnosia ↔ environmental sound agnosia (superior temporal and voice-selective pathways).

• Apraxia Axis: orobuccal praxis and speech-motor planning (AOS) (left frontal-insular).

Somatosensory/Body Schema:

• Agnosia Axis: tactile agnosia/astereognosis; autotopagnosia.

• Apraxia Axis: limb-kinetic and ideomotor failures (left IPL and connectors).

Social-Executive:

• Agnosia Axis: blunted interoceptive/affective signal recognition ("social agnosia").

• Apraxia Axis: disinhibition, utilization behavior, and set-shifting failure ("executive praxis"). These flow from salience-network and frontoinsular pathology.

7) How This Reframing Helps

1. Cognitive Ecology: Instead of "is this aphasia or apraxia?" we ask: along which agnosia/apraxia axes - and in which modality - does the patient fail? This reduces pseudo-dissociations created by task design and foregrounds multimodal convergence.

2. Anatomical Precision: Grouping deficits by axis predicts tract involvement (e.g., ILF for visual associative agnosia; SLF/IFOF for praxis/tool use; premotor/SMA for AOS), guiding imaging readouts and neuromodulation targets.

3. Neurodegenerative Patterning: The "mixture" view anticipates the characteristic blends in PCA (visual agnosia + constructional/optic apraxia), nfvPPA (AOS + grammatical sequencing), svPPA (conceptual agnosia), and bvFTD (social-executive praxis collapse).

4. Trial Endpoints: Axis-specific composites (e.g., a praxis battery aligned to dorsal fronto-parietal connectivity; a multimodal agnosia index aligned to ventral streams) may be more sensitive than omnibus cognitive screens for early-stage change. (Conceptual inference from the cited network and tractography literature.)

8) Limitations and Scope

Not all phenomena reduce cleanly to agnosia/apraxia. Primary arousal disorders, primary motor unit disease, or diffuse subcortical states can mimic these axes. Even within the cortex, neglect’s motor-intentional and perceptual-attentional components straddle our taxonomy. Our claim is pragmatic: for cortical syndromes, an agnosia x apraxia grammar offers high coverage and mechanistic traction.

Methods Note (Sources and Historiography)

Foundational sources include Freud (1891) on agnosia, Lissauer (1890) on agnosia subtypes, Liepmann (1900-1908) on apraxias, and Geschwind (1965) on disconnection. Modern scaffolding draws on dual visual streams and intrinsic network models (DMN, SN). Subtype-specific evidence comes from lesion-symptom mapping, tractography, and consensus criteria (e.g., PPA).

Selected References (Representative)

1. Freud S. Zur Auffassung der Aphasien (1891) - coined "agnosia."
2. Lissauer H. (1890) - apperceptive vs associative agnosia.
3. Liepmann H. (1900-1908) - ideomotor/ideational/limb-kinetic apraxias.
4. Geschwind N. (1965) - disconnection syndromes.
5. Goodale & Milner (1992) - perception-action streams.
6. Raichle/DMN and Buckner et al. (2005-2015) - network targets in AD.
7. Seeley et al. (2007, 2009-2013) - salience network; VEN vulnerability in bvFTD.
8. Gorno-Tempini et al. (2011) - PPA classification consensus.
9. Mandelli et al. (2014), Josephs et al. (2013) - AOS/nfvPPA tract and gray-matter correlates.
10. Rosenzopf et al. (2022) - praxis disconnection network.
11. Crutch et al. (2012) - PCA review.