Brain Overview
The brain regions most relevant to psychiatric illness are the prefrontal cortex (executive function, impulse control), the limbic system (emotion, memory, fear), the basal ganglia (habit, reward, movement), the hypothalamus & brainstem (autonomic, stress, sleep), and the monoaminergic nuclei of the brainstem (locus coeruleus, raphe, VTA, substantia nigra) that project widely.
| Region | Primary Psych Role |
|---|---|
| Prefrontal cortex (PFC) | Executive function, decision-making, inhibition of limbic drive |
| Amygdala | Fear, threat detection, emotional salience |
| Hippocampus | Declarative memory; atrophies in chronic stress/depression |
| Anterior cingulate | Error monitoring, emotional regulation, attention |
| Nucleus accumbens | Reward, motivation — hijacked in addiction |
| Hypothalamus | HPA axis, sleep, appetite, temperature |
| Locus coeruleus | Source of norepinephrine — arousal, panic |
| Raphe nuclei | Source of serotonin — mood, sleep, appetite |
| VTA / substantia nigra | Source of dopamine — reward, movement |
Prefrontal Cortex (PFC)
The PFC is the brain's executive — it plans, inhibits impulses, and regulates emotion by top-down control of the limbic system. It's the last brain region to mature (not fully myelinated until ~25 years old), which is why adolescents are biologically primed for risk-taking.
Subdivisions
- Dorsolateral PFC (DLPFC) — working memory, cognitive control. Hypoactive in depression and schizophrenia (negative symptoms).
- Ventromedial PFC (vmPFC) — emotional decision-making, value. Damaged in classic case of Phineas Gage → disinhibition.
- Orbitofrontal cortex (OFC) — reward evaluation, social behavior. Dysfunction → OCD, impulse disorders.
Limbic System
The limbic system is a ring of structures around the brainstem that processes emotion, memory, and motivation. Papez circuit: hippocampus → fornix → mammillary bodies → anterior thalamus → cingulate → back to hippocampus.
Amygdala
Almond-shaped cluster in the anterior temporal lobe. The brain's threat detector — tags stimuli with emotional significance, especially fear.
Key Functions
- Fear conditioning (Pavlovian)
- Fight-or-flight initiation (projects to hypothalamus → sympathetic activation)
- Consolidation of emotional memory (with hippocampus)
Clinical Correlations
- Hyperactive in anxiety, PTSD, panic disorder
- Hypoactive / lesioned → Klüver-Bucy syndrome (hyperorality, hypersexuality, docility, visual agnosia)
- SSRIs and benzodiazepines reduce amygdala reactivity
Hippocampus
Seahorse-shaped structure in the medial temporal lobe. Essential for declarative (explicit) memory formation and spatial navigation.
Clinical Correlations
- Bilateral damage → anterograde amnesia (classic: patient H.M.)
- Atrophy in chronic depression, PTSD, Cushing's, Alzheimer's
- One of two regions with adult neurogenesis — SSRIs promote hippocampal neurogenesis (hypothesized mechanism of delayed antidepressant response)
Anterior Cingulate Cortex (ACC)
Wraps around the corpus callosum. Bridges cognition and emotion. Two functional subdivisions:
- Dorsal ACC — cognitive control, error monitoring, attention (active during Stroop task)
- Subgenual ACC (Area 25) — affective regulation. Hyperactive in depression; target of deep brain stimulation for treatment-resistant MDD.
Basal Ganglia
Cluster of subcortical nuclei (caudate, putamen, globus pallidus, subthalamic nucleus, substantia nigra) involved in movement, habit, and reward.
| Structure | Psych Relevance |
|---|---|
| Caudate | Hyperactive in OCD (cortico-striatal-thalamic loop); atrophies in Huntington's |
| Putamen | Habit learning; involved in tics/Tourette's |
| Nucleus accumbens (ventral striatum) | Reward and addiction hub — terminal of mesolimbic dopamine |
| Substantia nigra pars compacta | Source of nigrostriatal dopamine → movement. Degenerates in Parkinson's. Blocked by antipsychotics → EPS. |
Thalamus & Hypothalamus
Thalamus
Relay station for nearly all sensory info to cortex (except smell). "Gating" dysfunction is implicated in schizophrenia (sensory-gating deficits explain overwhelming stimulation).
Hypothalamus
Master regulator of homeostasis: temperature, appetite, thirst, circadian rhythm, autonomic tone, and the HPA axis.
| Nucleus | Function |
|---|---|
| Suprachiasmatic | Circadian pacemaker — disturbed in depression, bipolar, shift-work disorder |
| Ventromedial (VMH) | Satiety — "VentroMedial = Very Much Full" |
| Lateral (LH) | Hunger — "Lateral = Lean" (lesion causes anorexia) |
| Paraventricular (PVN) | Releases CRH → drives HPA axis |
| Arcuate | Leptin/ghrelin sensing; disrupted in eating disorders |
HPA Axis — The Stress Highway
The central stress-response system, dysregulated in depression, PTSD, anxiety, and chronic illness.
Pathway
- Stress perceived → hypothalamic PVN releases CRH
- CRH → anterior pituitary → ACTH
- ACTH → adrenal cortex → cortisol
- Cortisol negative-feedback at hypothalamus & pituitary
Pathologic States
- Depression — HPA hyperactivity, flattened diurnal cortisol curve, blunted dexamethasone suppression
- PTSD — paradoxically LOW cortisol with enhanced negative feedback
- Chronic stress — hippocampal atrophy (cortisol neurotoxicity), amygdala hypertrophy
- Cushing's — psych symptoms in ~50% (depression, mania, psychosis, cognitive decline)
Reward Circuitry — The Mesolimbic System
Dopaminergic pathway from VTA (ventral tegmental area) → nucleus accumbens → prefrontal cortex. This circuit encodes "wanting" and motivation, and is hijacked by every addictive drug.
Four Dopamine Pathways
| Pathway | From → To | Function | Dysfunction |
|---|---|---|---|
| Mesolimbic | VTA → NAcc | Reward, motivation | ↑ = positive sx of schizophrenia, addiction |
| Mesocortical | VTA → PFC | Executive, cognition | ↓ = negative sx of schizophrenia |
| Nigrostriatal | SNc → striatum | Movement | ↓ = Parkinson's, EPS from D2 blockers |
| Tuberoinfundibular | Hypothalamus → pituitary | Inhibits prolactin | Blocked by antipsychotics → hyperprolactinemia |
Default Mode Network (DMN)
A set of regions active when the mind is at rest and self-referential — medial PFC, posterior cingulate, precuneus, angular gyrus. Involved in rumination, self-reflection, and mind-wandering.
- Hyperactive DMN — depression (rumination), anxiety (worry)
- Disrupted connectivity — schizophrenia, autism
- Mindfulness-based therapies and psychedelics (ketamine, psilocybin) quiet DMN overactivity
Clinical Correlations — One-Liner Summary
| Disorder | Key Neuroanatomical Finding |
|---|---|
| Depression | ↓ hippocampal volume, ↑ subgenual ACC, HPA hyperactivity, ↓ DLPFC |
| Anxiety / PTSD | Amygdala hyperactivity, ↓ vmPFC top-down control |
| OCD | Caudate / OFC / ACC hyperactivity (CSTC loop) |
| Schizophrenia | ↓ brain volume, enlarged ventricles, ↓ DLPFC, aberrant mesolimbic DA |
| Addiction | NAcc sensitization, PFC hypoactivity |
| ADHD | ↓ PFC + striatum volumes, delayed cortical maturation |
| Autism | Altered connectivity, ↓ mirror-neuron / social-brain activation |
| Alzheimer's | Hippocampal & entorhinal atrophy first |