L16: Neurogenesis and Brain Stimulation

Neurogenesis in the DG

new cells generate in DG in Hippo, and mature within a few weeks

Maturation of newborn cells

• 1-6% cell turnover per month

• Neurogenesis is decreased by stress, depression, and normal aging

• Neurogenesis is increased by excercise, antidepressants like Prozac, ETC, and Estrogen

effects of stress and antidepressants on neurogenesis in DG

stress decreases # of baby neurons, antidepressant increase # of baby neurons

effects of chronic stress on neurogenesis in DG

chronic stress reduces DG neurogenesis, but these deficits appear to recover

effects of hippocampal dependent learning

Neurogenesis is increased by extensive hippocampal dependent learning (i.i., trace, but not decay conditioning)

• study: trace decay needs hippo, delay conditioning does not

• found: 30 days after learning, there were more surviving cells in hippo if you did a task that involves hippo (trace conditioning)

When does neurogenesis occur in humans?

• autopsy hippocami - thousands of immature neurons in the DG, throughout the lifespan

• autopsy hippocampi (ages prior to birth to 77) - new cells only observed in first year of life

• → still controversial, reduced in aging and so far only indirectly linked to memory

neurogenesis summary

1. New cells are generated in the DG of the hippocampus (probably in humans? ideally suited to support episodic memory)

2. Neurogenesis is related to memory (e.g., stress, depression, aging, exercise, antidepressants etc)

? can injection of stem cells or molecular therapists (neurotropic factors) reverse memory declines?

Brain Stimulation - clinical reports during surgery

reviewing showing electrical stimulation leading to reminiscences (e.g., hearing an old song, seeing a place from the past, recalling an event)

• hippocampus/anygdala stim. produced episodic memories

• perirhinal and entorhinal cortex stim. produced reports of familiar objects, semantic memories & dreams

• lateral temporal lobe (auditory semantics) and inferior temporal lobe (visual semantic)

Can Brain Stimulation Improve Memory

Methods:

1. Deep Brain Stimulation (DBS) - electrodes implanted for clinical purposes in the brain or on the cortical surface

2. Transcranial Magnetic Stimulation (TMS) - high intensity magnetic fields on scalp used to induce electrical currents in cortex

3. Transcranial Direct Current Stimulation (tDCS) - electrical currents applied directly to the scalp

Stimulation may impact memory immediately by altering firing rates, or by altering neural plasticity

Deep Brain Stimulation (DBS) during encoding and retrieval

Encoding

• entorhinal and hippocampal stimulation impaired spatial navigation and verbal memory encoding

• parahippo, cingulate and frontal cortex stimulation had no effect

Retrieval

• hippocampal stimulation disrupt recognition retrieval for objects, words & faces (lateralized effect)

→ DBS of MTL disrupts encoding and retrieval

Deep Brain Stimulation (DBS) of various locations

Stimulation of various locations in 22 patients during word encoding

• stimulation of lateral temporal cortex increased recall

• stimulation of other regions (i.e., hippo, parahippo, prefrontal) led to small reductions in recall

Same paradigm, but identified a pattern of successful encoding activity (i.e., more high than low frequency oscillations), then stimulated (.5s) when this signal decreased

• lateral temporal cortex stimulations led to better recall

• → DBS of lateral temporal cortex may enhance encoding?

  (does it impact memory processing per se, or semantic processing, vigilance , or attention?)

DBS stimulation of various locations during word encoding

• stimulation of lateral temporal cortex increased recall

• stimulation of other regions (i.e., hippo, parahippo, prefrontal) led to small reductions in recall

• identified a pattern of successful encoding activity (i.e., more high than low frequency oscillations), then stimulated (.5s) when this signal decreased - lateral temporal cortex stimulation led to better recall

→ DBS of lateral temporal cortex may enhance encoding? (does it impact memory processing per se, or semantic processing, vigilance, or attention?)

Continuous fornix stimulation (vs sham) for 12 months in patients with mild AD

• Increased metabolism at 6 months

• no effect on cognitive measures of AD (but trend to impair if <65 years and improve if >65??)

→ Chronic DBS of the fornix may slow progression of AD in some patients, but increase progression in others?

Transcranial Magnetic Stimulation (TMS) (neural)

• TMS (high and low frequency, over frontal/temporal/parietal regions, pre-encoding/post-encoding) sometimes improves and sometimes reduces memory

• → TMS may impact explicit memory, but its effects are complex

• (Note: TSM of visual cortex may impact visual WM)

Transcranial Magnetic Stimulation (TMS) (positive)

over left parietal lobe (connected to hippo)

• increased cued recall for new face-word pairs

of the precuneus (medial parietal) in AD patients)

• enhanced visual LTM

→ Chronic TMS stimulation of parietal cortex can improve memory (memory, semantic processing, attention?)

tDCS

• meta-analysis of 20 long term verbal memory DCS studies. “Left ventrolateral prefrontal and temporo-parietal sites appeared most likely to enhance episodic memory, although any significant effects were based on findings from single studies only.”

• meta-analysis of 38 long term memory tDCS studies - “together, the effects of tDCS were small and non-significant.” The effects were slightly larder for recall than recognition, and the largest over left parietal sites.

• → so far, tDCS does not appear to be very effective

Summary of the three types of brain stimulation

1. DBS of MTL impairs memory, but lateral temporal may help

2. Repeated TMS of parietal cortex may improve memory

3. tDCS does not appear to do much

Sci-fi: brain stimulators for AD patients?