Neuropsychiatry and Behavioral Neurology

Neuropsychiatry: Scope, Roots, Terminology

• Definition & Scope
  • Psychiatric subspecialty focused on psychological & behavioral manifestations of acquired brain disease (“organic mental disorders”).
  • Interfaces with Cognitive & Behavioral Neurology; together study cognitive/affective sequelae of neurologic pathology.
• Why term “organic” persists
  • Clear bedside/lab pathology in acquired disorders (stroke, TBI, epilepsy, etc.) distinguishes them from idiopathic psychiatric conditions whose biomarkers are typically sub-threshold or genetic/developmental.
• Historical Milestones
  • Early 19th-century asylum physicians viewed virtually all insanity as brain disease (paresis, epilepsy, ID, alcoholism).
  • Neurology initially outpatient-oriented, managing mild mood/anxiety cases.
  • 1965: Norman Geschwind revives continental “behavioral neurology” tradition (Jackson, Wernicke, Liepmann, etc.).
• Take-home: Modern neuropsychiatry re-examines historical anatomical thinking with contemporary imaging, genetics, network science.

Foundations of the Neuropsychiatric Brain

• Chemical vs. Circuit View
  • “General-psychiatric brain” ≈ diffuse neurotransmitter soup; anatomic specificity scant.
  • “Neuropsychiatric brain” = differentiated circuits, lateralization, white-matter tracts with testable lesion–behavior links.

Lateralization Highlights

• Left vs. Right
  • Language, praxis → L hemisphere main; visuospatial & emotion perception → R hemisphere.
  • Broca’s pars opercularis & planum temporale usually larger L>R (handedness modifies).
• Autonomic & Endocrine Asymmetry
  • R insula → sympathetic cardiac drive; L insula → parasympathetic.
  • L-sided limbic epilepsy linked to polycystic ovary syndrome; hemisphere side influences post-stroke cardiac risk & immune changes.
• Emotion
  • R hemisphere pre-potent for perception/production of affect (aprosodia when damaged).
  • Valence theory (L=positive, R=negative) only partly supported.

Fronto-Subcortical Circuits (“Loops”)

• Basic schema: Cortex → Striatum → Globus Pallidus/SNr → Thalamus → Cortex (closed, parallel).
• Key loops & clinical pictures
  • Dorsolateral PFC ↔ dorsolateral caudate ⇒ Executive dysfunction, working-memory deficits; lesions in TBI, small-vessel white-matter disease, PD.
  • Lateral Orbitofrontal ↔ ventromedial caudate ⇒ Impulsivity, disinhibition, anosmia neighbour sign.
  • Medial Orbitofrontal ↔ ventromedial caudate ⇒ Poor judgment, social decision-making.
  • Anterior Cingulate ↔ ventral striatum ⇒ Apathy, abulia, akinetic mutism; target of cingulotomy for OCD.

Limbic System Refresher

• Core circuit: Papez – hippocampus → fornix → mamillary bodies → anterior thalamus → cingulate → entorhinal cortex → hippocampus.
• Amygdala–OFC loop drives affect & social behaviour.
• Clinical gems
  • >50\% adult epilepsy = mesial temporal; “voluminous mental state” (déjà vu, micro/macropsia).
  • Explicit memory consolidated via hippocampus; limbic threshold low for seizures.

Cerebellum Beyond Motor

• Cerebro-cerebellar loops mirror BG loops (crossed, via thalamus).
• Cognitive/affective (“Schmahmann”) syndrome: executive deficits, language (R hemi), visuospatial (L hemi), irritability/lability (vermis lesions).
• Caveat: crossed cerebellar diaschisis can confound localization.

Cerebral Cortex Organization

• Hierarchical flow
  • Primary → unimodal association → heteromodal (PFC, PPC, lat. temporal, parahippocampal).
  • Hippocampal outputs reach only association cortices – shields early sensory processing.
• Double Dissociations validate modular processing (e.g., living-vs-artifact naming).
• Visual streams: Dorsal “where” (parietal; Balint, optic ataxia) vs. Ventral “what” (inferotemporal; agnosias, prosopagnosia).

White Matter & Connectivity

• Volume: \approx42\% of human cerebral hemispheres.
• Major intra-hemispheric tracts: arcuate/superior longitudinal; uncinate/inferior occipitofrontal; cingulum.
• Projection systems: internal capsule, corticospinal, thalamic peduncles, medial forebrain bundle.
• Disconnection syndromes
  • Anterior callosal lesion → left-hand apraxia, tactile anomia.
  • Posterior callosal (splenium) + L occipital stroke → alexia without agraphia.
• Binswanger & CADASIL: small-vessel white-matter loss → subcortical dementia (slowed processing, executive failure).

Functional Networks (fMRI Resting-State)

• Default Mode (DMN): medial PFC, PCC, angular → episodic memory; atrophy in AD.
• Salience: ant. cingulate + insula, amygdala, ventral striatum → bvFTD target.
• Central Executive: DLPFC–parietal → working memory.
• Lesion-network mapping: overlapping connectivity explains variable lesion loci for same symptom (e.g., mania, hallucinations).

Modularity Debate

• Evolutionary “modules” vs. selectively distributed networks.
• Plastic re-allocation across development (e.g., Williams syndrome number→language shift).
• Clinical moral: focal-lesion analogies to idiopathic psychiatric disorders require caution.

Clinical Evaluation Strategy

Neuropsychiatric History Toolkit

• Always ask about systemic diseases, traumatic brain injury, seizures, sleep, substances, meds, family hx.
• Red flags warrant deeper organic work-up: late onset, rapid progression, neurological signs, atypical features, cognitive red flags.
• Specialized probes
  • Paroxysmal limbic phenomena (déjà vu, forced emotions).
  • Head-injury chronology: LOC, retro-/anterograde amnesia.
  • Prodrome → aura → ictus → post-ictal course for spells.
  • Appetite/sexual/personality shifts suggest frontotemporal or hypothalamic syndromes.
• Handedness matters for lesion interpretation – ask task-specific usage.

Physical & Neurologic Examination Pearls

General/dysmorphology

• Minor physical anomalies (Waldrop scale) – developmental disorders.
• Skin markers: neurocutaneous syndromes, lupus malar rash, livedo reticularis (Sneddon).

Cranial Nerves & Motor

• Hyposmia → orbitofrontal/PD/AD red flag; test with scented balm.
• Eye movement patterns: slowed saccades (HD), downgaze paresis (PSP), visual grasp (frontal release).
• Speech taxonomy (Table in text): aphemia, apraxia of speech, dysarthrias, aprosodia, palilalia, etc.
• Motor tone patterns: spastic (pyramidal), lead-pipe + cogwheel (extrapyramidal), paratonia (diffuse/frontal).
• Tremor classification: rest (PD), postural (essential), intention (cerebellar), asterixis \Rightarrow metabolic/toxic.

Soft Signs & Primitive Reflexes

• Mirror movements, face–hand extinction, Myerson, Hoffmann, grasp vs. avoidance (parietal).

Focal Neurobehavioral Syndromes

Dementia Variants

• AD trajectory: entorhinal → temporoparietal → PFC; posterior cortical atrophy & executive variant recognized.
• bvFTD: orbitofrontal/insula network atrophy, disinhibition, empathy loss, early <65\text{ y}.
• Vascular: subcortical slowing + executive failure. Strategic infarcts (angular gyrus, thalamus).

Delirium

• Global slowing on EEG; BUT focal strokes (R post-sup temporal, bilateral occipito-temporal) can mimic delirium.

Aphasia Bedside Grid (see Table)

• Examine 6 domains (speech, naming, comp, repetition, reading, writing).
• Conduction = poor repetition; transcortical = spared repetition.
• Ideomotor apraxia often co-occurs.

Attention & Working Memory

• Vigilance (CPT-style “raise hand on A after D”).
• Working memory tests: alphanumeric sequencing \ge15 alternations normal; digit span \ge5.
• Hemineglect – search arrays; Balint triad.

Amnesia Typology

• Hippocampal/thalamic damage → rapid forgetting, poor cued recall; recognition disproportionately spared in frontal “retrieval” deficit.

Visuospatial & Executive Panels

• Copy intersecting pentagons; Poppelreuter overlapping figures; route description.
• Executive probes: go/no-go tapping, ring-fist, FAB, fluencies (semantic vs. phonemic), Trail-making, Stroop.

Mood & Affective Dysregulation

• Right-hemisphere lesions: aprosodia, emotion recognition deficits.
• Pathologic laughing/crying (pseudobulbar) – corticobulbar disinhibition network.
• Apathy vs. depression: lack of negative affect; dopaminergic Rx sometimes helpful.
• Mania loci: right orbitofrontal, anterior limbic, thalamic.

Abnormal Agency & Social Cognition

• Alien hand (parietal → ownership loss; SMA/callosal → autonomous grasp/conflict).
• Theory-of-mind deficits: medial PFC, right TPJ, amygdala – autism, FTD.

Paraclinical Investigations

Structural Imaging

• CT: rapid, hemorrhage & bone; MRI superior for white matter & mesial temporal sclerosis; gradient echo for microbleeds.
• Volumetry (hippocampus), DTI (tracts), SWI (microbleeds), MRA (large vessels), DAT-scan for nigrostriatal loss.

Functional Imaging

• SPECT/PET: AD temporoparietal hypometabolism; DLB shows occipital hypoperfusion.
• fMRI resting-state for research; lesion-network mapping.

EEG & Evoked Potentials

• Single routine EEG detects 30\text{–}50\% epilepsy; serial + sleep \to 70\text{–}80\%.
• Diffuse slowing distinguishes delirium from primary psychosis; periodic complexes & DWI “cortical ribbon” \to CJD.

CSF & Labs

• Dementia screen: CBC, CMP, B_{12}, TSH, RPR/FTA in high-prevalence regions.
• Autoimmune encephalitis work-up: CSF antibodies (NMDAR, LGI1, CASPR2, VGKC), EEG sensitivity >95\% for anti-NMDAR (slowing).
• AD biomarkers: ↓Aβ + ↑tau / phospho-tau in CSF.
• Metabolic/Genetic red-flags (see Table): VLCFA (ALD), ceruloplasmin (Wilson), cholestanol (CTX), etc.

Neuropsychological Assessment Principles

• Clarify consult question (capacity, baseline IQ, lateralization, disability).
• Test batteries inform real-world function but ecologic validity limited (orbitofrontal syndromes!).

Brain Biopsy

• Reserved for unclear inflammatory/neoplastic cases when therapy hinges on pathology (e.g., PACNS).

Common Neuropsychiatric Disorders & Management Pearls

Epilepsy

• Distinguish focal impaired-awareness seizures vs. PNES vs. panic; timeline: prodrome → aura (core seizure) → ictus → postictal.
• Psychoses: ictal (twilight), post-ictal (days), inter-ictal chronic; forced normalization phenomenon.
• Gastaut–Geschwind personality: hypergraphia, viscosity, hyposexuality – controversial.

Traumatic Brain Injury (TBI)

• Cognitive/behavioral → disinhibition, irritability > motor deficits for families.
• Even brief LOC or none can lead to chronic deficits; cumulative prior TBIs amplify.

Movement Disorders

• PD: depression, anxiety, ICDs fluctuate with dopaminergic dosing; psychosis from dopamine agonists.
• PSP: vertical gaze palsy, axial rigidity, frontal executive syndrome.

Developmental Disabilities in Adults

• Do not diagnostic-overshadow; late-onset mood/psychosis possible.
• Genetic testing & MRI often under-utilized; behavioural phenotypes (Prader-Willi, Williams, 22q11 deletion).

Infectious & Autoimmune Encephalopathies

• HSV PCR CSF – start acyclovir empirically if suspicion.
• Autoimmune limbic encephalitis: subacute memory + anxiety/seizures; paraneoplastic link (ovarian teratoma in NMDAR).

Conversion / Functional Neurologic Symptoms

• Hoover sign reliable; co-morbid organic disease common (PNES + epilepsy).
• Management: alliance, address trauma/psych stress, treat co-morbid mood/anxiety.

Differential-Diagnosis Quick Tables

Dementia Neuro Exam Clues (selected)

• Oculomotor palsy → PSP, NPC, MS.
• Pyramidal + ataxia → B_{12} deficiency, leukodystrophies.
• Extrapyramidal + hallucinations → DLB, PD dementia.
• Cerebellar + neuropathy → CTX, Mitochondrial, SCA.

Inborn Errors w/ Psychiatric Presentations (high-yield)

• Wilson: psychosis, mood lability, KF rings, \uparrow urinary Cu.
• Niemann–Pick C: psychosis + vertical gaze palsy, splenomegaly.
• Urea-cycle defects: acute confusion after protein load, \uparrow ammonia.

Synthesizing the Neuropsychiatric Outlook

• Think systems & circuits, not isolated neurotransmitters.
• Bedside history/exam remain highest yield “tests”; targeted labs/imaging follow hypotheses.
• Complex psychiatric syndromes rarely map to single loci; instead, network dysfunction & developmental plasticity explain variance.
• Neuropsychiatry bridges neurology & psychiatry, aiming at dual goals:
  • 1️⃣ Identify treatable brain disease.
  • 2️⃣ Use cognitive neuroscience to parse symptoms into mechanistic processes for better therapies.