Frontal Lobe Dysfunction & Neurotransmitter Pathways

Frontal Lobe Dysfunction

• The Primary motor cortex
  • Contra lateral motor control
• The medial frontal cortex
  • Arousal and motivation – Abulic (Apathy & inattention)
• The orbital frontal cortex
  • Modulate Behavior – Labile, euphoric, facetious, vulgar
• The left postero-inferior frontal cortex (Broca’s)
  • Language – expressive Aphasia
• The dorsolateral frontal cortex
  • Working memory & dysexecutive syndrome

Disorders that Affect the Forebrain

Region

• Cerebral cortex
  • Disorder: depression, Huntington’s disease, mania
• Cerebrum
  • Disorder: epilepsy, stroke
  • frontal lobe
    • Disorder: Alzheimer’s disease, depression, mania, schizophrenia
  • parietal lobe
    • Disorder: Alzheimer’s disease
  • temporal lobe
    • Disorder: Alzheimer’s disease, depression, mania
• Limbic system
  • amygdala
    • Disorder: mania
  • hippocampus
    • Disorder: depression, Alzheimer’s disease, mania

Serotonin Pathways

Dopamine Pathways

• Frontal cortex
• Nucleus accumbens
• VTA
• Striatum
• Substantia nigra
• Hippocampus
• Raphe nuclei

Functions

• Reward (motivation)
• Pleasure, euphoria
• Motor function (fine tuning)
• Compulsion
• Perseveration

Functions

• Mood
• Memory processing
• Sleep
• Cognition

Serotonin and Depression

• Serotonin transmission – Caudal raphe nuclei and Rostral raphe nuclei is reduced in depression
• Increasing the levels of serotonin in these pathways, by reducing serotonin reuptake = treatment

Serotonin and Schizophrenia

• Dorsal raphe nuclei – Substantia Nigra
• Rostral raphe nuclei – cerebral cortex, limbic regions, and basal ganglia
• The up-regulation of Serotonin pathways leads to the hypofunction of dopamine pathways = negative symptoms
• The serotonergic nuclei in the brainstem that give rise to descending serotonergic axons remains unaffected in schizophrenia

Dopamine Pathways

• mesolimbic tract
• nigrostriatal tract
• mesocortical tract
• tuberoinfundibular tract
• VTA
• HT

Frontal Lobe & Schizophrenia

• REDUCED NMDA GLUTAMATE RECEPTORS CAUSING COGNITIVE SYMPTOMS
• RESPONSIBLE FOR NEGATIVE SYMPTOMS
• ANATOMICAL ABNORMALITY OF PREFRONTAL CORTEX
• MRI & PET SHOWS FUNCTIONAL DIFFERENCE IN BRAIN ACTIVITY IN FRONTAL LOBE, HIPPOCAMPUS, TEMPORAL LOBE
• PET SHOWS LESS FRONTAL ACTIVITY DURING WORKING MEMORY RELATED TO NEUROCOGNITIVE DEFECTS

OCD

• ALTERED FUNCTION IN NEURO CIRCUIT
• INCREASED BLOOD FLOW & METABOLISM IN FRONTAL LOBE
• COMPULSIVE HOARDING: Compulsive hoarding or pathological hoarding or disposophobia is the excessive acquisition of possessions, even if the items are worthless, hazardous, or unsanitary.
• DAMAGE TO RT MEDIAL PREFRONTAL CORTEX CAUSE HOARDING

DEMENTIA

• COGNITIVE IMPAIREMENT, MEMORY IMPAIREMENT, PERSONALITY CHANGES - THOUGHT TO BE DUE TO FRONTAL INVOLVEMENT

ADHD

• GENERAL REDUCTION OF BRAIN VOLUME, BUT PROPORTIONALLY GREAT REDUCTION OF LT PREFRONTAL CORTEX
• RECENT RESEARCH SHOWS FOLLOWING FOUR CONNECTED FRONTOSTRIATAL REGIONS PLAY A ROLE IN ADHD-lateral prefrontal cortex, Dorsal anterior cingulate, caudate, Putamen
• DELAYED DEVELOPMENT OF FRONTAL CORTEX, TEMPORAL LOBE & FAST MATURITY OF MOTOR CORTEX SEEN
• THIS CONTRIBUTES SLOW BEHAVIOURAL CONTROL & ADVANCED MOTOR DEVELOPMENT LEADS TO FIDGETINESS, THAT IS CHARACTERISTIC OF ADHD
• PET SHOWS LOW PERFUSION AND METABOLISM OF FRONTAL AREA