A 45-year-old man is brought by his wife with a complaint of an ongoing progressive history of memory problems for 6 months. He is an accountant by profession. He has difficulty remembering things and events, which has affected his job. He began using a diary to aid with remembering his agenda. His wife also says that he has wet his pants multiple times in the past 2 months and he avoids going out. He has been smoking 1 pack of cigarettes daily for the past 20 years. His past medical history is unremarkable. The vital signs include: blood pressure of 134/76 mm Hg, a pulse of 70 per minute, and a temperature of 37.0°C (98.6°F). His mini-mental state examination (MMSE) result is 22/30. His extraocular movements are normal. The muscle tone and strength are normal in all 4 limbs. The sensory examination is unremarkable. He has an absent Romberg’s sign. He walks slowly, taking small steps, with feet wide apart as if his feet are stuck to the floor. The CT scan of the head is shown in the image. What is the most likely diagnosis of the patient?

Early-onset Alzheimer’s disease

A 21-year-old man presents to the emergency room requesting surgery to remove "microchips," which he believes were implanted in his brain by "Russian spies" 6 months ago to control his thoughts. He also reports hearing the "spies" talk to each other through embedded "microspeakers." You notice that his hair appears unwashed and some of his clothes are on backward. Urine toxicology is negative for illicit drugs. Which of the following additional findings are you most likely to see in this patient during the course of his illness?

Asociality, flat affect, and alogia

Anhedonia, guilty rumination, and insomnia

Grandiose delusions, racing thoughts, and pressured speech

Amnesia, multiple personality states, and de-realization

Intrusive thoughts, ritualized behaviors, and anxious mood

A 67-year-old female is brought to the emergency room by her son for unusual behavior. She moved into her son’s house three years ago after her husband passed away. The son reports that when he returned home from work earlier in the day, he found his mother minimally responsive. She regained consciousness soon after his arrival and did not recall the event. The son also reports that for the past two years, his mother has had trouble remembering names and addresses. She still goes shopping on her own and cooks regularly. Her past medical history is notable for major depressive disorder, diabetes mellitus, and hypertension. She takes clomipramine, glyburide, lisinopril, and hydrochlorothiazide. She recently saw her primary care provider who adjusted some of her medication dosages. Her temperature is 99°F (37.2°C), blood pressure is 135/75 mmHg, pulse is 80/min, and respirations are 18/min. On examination, she is easily distractible with disorganized speech. She does not recognize her son and thinks that her intravenous line is a rope. She says she feels fine and would like to go home. Brain imaging would likely reveal which of the following?

Multiple ischemic sites and microhemorrhages

Focal atrophy of the frontal and temporal cortices

A 75-year-old woman presents to her primary care physician with her son because she is convinced that people are stealing from her. Her son claims she has been misplacing her medications and money throughout the house. She recently lost her husband to old age and has become reclusive and no longer wants people to visit. Physical examination is unremarkable and the patient is oriented to person, time, and place. A mini-mental status examination (MMSE) is performed and she has difficulty recalling words after 5 minutes and also has problems with serial subtraction. Which of the following is the most likely diagnosis in this patient?

Histrionic personality disorder

A 28-year-old male presents to his primary care physician with complaints of intermittent abdominal pain and alternating bouts of constipation and diarrhea. His medical chart is not significant for any past medical problems or prior surgeries. He is not prescribed any current medications. Which of the following questions would be the most useful next question in eliciting further history from this patient?

"Can you tell me more about the symptoms you have been experiencing?"

"Does the diarrhea typically precede the constipation, or vice-versa?"

"Is the diarrhea foul-smelling?"

"Please rate your abdominal pain on a scale of 1-10, with 10 being the worst pain of your life"

"Are the symptoms worse in the morning or at night?"

A 68-year-old man, accompanied by his wife, presents to his physician with cognitive decline and hallucinations. The patient’s wife tells that his cognitive impairment progressed gradually over the past 6 years, and first began with problems counting and attention. The hallucinations began approximately a year ago. The patient describes them as realistic and non-frightening; most often, he sees his cat accompanying him everywhere he goes. The patient’s wife also notes frequent episodes of staring spells in her husband and prolonged daytime napping. The blood pressure is 130/80 mm Hg with the orthostatic change to 110/60 mm Hg, heart rate is 75/min, respiratory rate is 13/min, and the temperature is 36.6°C (97.8°F). The patient is alert and responsive, but he is disoriented to time and place. He is pale and hypomimic. The cardiac, lung, and abdominal examinations are within normal limits for the patient’s age. The neurological examination is significant for a bilateral symmetrical cogwheel rigidity in the upper extremities. What would you most likely see on additional radiological investigations?

Decreased perfusion and dopaminergic activity in occipital lobes on PET

Multiple lacunar infarcts on MRI

Marked hippocampal atrophy on MRI

Hypoperfusion and hypometabolism in frontal lobes on SPECT

Pontine 'hot-cross bun' sign on MRI

Neuroimaging findings for USMLE Step 1: High-Yield Psychiatry Lessons

Structural Findings - Brain Blueprint Breakdown

Coronal MRI: Enlarged lateral ventricles in schizophrenia

Ventriculomegaly: Most consistent finding.
- ↑ in lateral and third ventricle volume.
- Represents a loss of surrounding brain parenchyma.
Reduced Brain Volume (Cortical Atrophy):
- Temporal Lobe: ↓ volume of the hippocampus, amygdala, and superior temporal gyrus. This impacts memory, emotional regulation, and auditory processing.
- Frontal Lobe: ↓ volume, particularly the dorsolateral prefrontal cortex (DLPFC). This is linked to executive dysfunction and negative symptoms (hypofrontality).
- Thalamus: ↓ size, disrupting its role as a key sensory and information relay center.

⭐ Enlargement of the cerebral ventricles is the most reliable and replicated structural neuroimaging finding in schizophrenia. This is due to a loss of brain tissue volume, not an overproduction of CSF.

Functional Findings - Firing Squad Fumbles

Hypofrontality: The hallmark functional finding, characterized by ↓ activity in the prefrontal cortex (PFC), especially the dorsolateral prefrontal cortex (DLPFC).
- This correlates strongly with the severity of negative symptoms (e.g., apathy, avolition, alogia).
- 📌 Mnemonic: Down Low PreFrontal Cortex → Deficient Logic, Planning, Feeling, Concentration.
Imaging Modalities:
- fMRI (functional MRI) & PET (Positron Emission Tomography) scans show ↓ blood flow and glucose metabolism in the frontal lobes, particularly at rest.
- During executive tasks (e.g., Wisconsin Card Sorting Test), a healthy brain shows ↑ frontal activation, but a schizophrenic brain shows blunted or paradoxical ↓ activation.

fMRI: Brain Connectivity Differences in Schizophrenia

⭐ High-Yield Pearl: While structural MRI might be normal, fMRI often reveals hypofrontality, especially in the DLPFC, during cognitive tasks. This functional deficit is linked to impaired executive function, a core feature of schizophrenia.

Symptom Correlation - Connecting Brain to Behavior

Cerebral Atrophy vs. Healthy Brain

Negative Symptoms (Alogia, Avolition): Linked to hypofrontality-decreased activity in the dorsolateral prefrontal cortex (DLPFC).
Positive Symptoms (Hallucinations, Delusions): Correlated with excess dopamine activity in the mesolimbic pathway.
Cognitive Deficits (Memory, Executive Function): Associated with hippocampal and temporal lobe volume reduction.

⭐ Wisconsin Card Sorting Test: A classic finding is hypofrontality (reduced DLPFC blood flow) during this executive function task, failing to "switch sets."

High-Yield Points - ⚡ Biggest Takeaways

The most consistent and replicated finding is enlargement of the lateral and third ventricles.

Expect decreased cortical volume, especially in the temporal and prefrontal lobes.

Functional imaging (fMRI, PET) often reveals hypofrontality-decreased activity in the prefrontal cortex, particularly during executive tasks.

Reduced volume of medial temporal lobe structures, including the hippocampus and amygdala, is common.

These findings are statistical associations, not diagnostic biomarkers; diagnosis remains clinical.

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