Characterization of Olfactory Amygdala Subregions

Overseen By Gregory Lane

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northwestern University

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

100 Participants Needed

Trial Summary

What is the purpose of this trial?

We aim to better understand the subregions of the human amygdala that receive direct projections from the olfactory bulb

Do I need to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Presenting Odors, Smell Retraining Therapy, SRT, Olfactory Training?

Research suggests that the amygdala, a part of the brain involved in processing emotions and memory, plays a key role in how we remember and react to smells. This implies that treatments focusing on olfactory training could potentially improve smell-related memory and emotional responses, which might be beneficial for people with smell disorders. ^{1 2 3 4 5}

Is olfactory training safe for humans?

The research articles provided do not contain specific safety data for olfactory training or related treatments in humans. ^{1 5 6 7 8}

How does this treatment differ from other treatments for olfactory amygdala conditions?

This treatment is unique because it focuses on the specific subregions of the olfactory amygdala, which are involved in distinct olfactory functions and emotional processing. Unlike other treatments, it may target the primary olfactory areas directly, potentially influencing rapid motor responses, reward processing, and multisensory integration of olfactory information. ^{1 9 10 11 12}

Eligibility Criteria

This trial is for individuals over the age of 18 who are interested in participating in a study to understand brain activity related to sense of smell.

Inclusion Criteria

I am older than 18 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Baseline Assessment

Participants undergo high-resolution diffusion-weighted imaging and fMRI to establish baseline anatomical and functional characteristics of the olfactory amygdala subregions

8 weeks

4 visits (in-person)

Experimental Procedures

Participants engage in olfactory tasks while brain activity is recorded using fMRI and intracranial electrophysiology, including electrical stimulation of the amygdala

Variable over 3 years

Multiple visits (in-person)

Follow-up

Participants are monitored for any long-term effects of the procedures and to assess the stability of olfactory perception changes

6 months

Treatment Details

Interventions

• Presenting Odors

Trial Overview The study involves presenting different odors to participants while their brain activity is recorded, focusing on specific areas within the amygdala.

Participant Groups

Group I: record brain activity while smelling odors Experimental Treatment 1 Intervention

Record brain activity while smelling odors

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Findings from Research

The medial amygdala (MeA), cortical amygdala (CoA), and periamygdaloid complex (PAC) are distinct subregions of the amygdala that receive direct input from the olfactory bulb, suggesting they play unique roles in processing olfactory information.

Using resting-state fMRI, the study identified that these subregions have distinct functional networks, with the MeA potentially linked to rapid motor responses to smells, the CoA associated with reward processing related to olfactory stimuli, and the PAC involved in integrating olfactory information with other senses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Primary Olfactory Amygdala Subregions Form Distinct Functional Networks, Suggesting Distinct Olfactory Functions. Noto, T., Zhou, G., Yang, Q., et al.[2022]

Patients with unilateral amygdala damage showed specific impairments in matching odors with names, indicating the amygdala's role in olfactory memory, while their recognition of odors remained intact.

Bilateral amygdala damage led to severe deficits in both odor-name matching and odor-odor recognition, highlighting the amygdala's critical importance in processing and remembering smells, distinct from general memory functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A specific role for the human amygdala in olfactory memory. Buchanan, TW., Tranel, D., Adolphs, R.[2019]

In a study involving 19 patients who had undergone unilateral medial temporal-lobe resection (MTLR) and 19 healthy controls, it was found that patients with MTLR did not exhibit enhanced memory for emotionally arousing odors compared to nonarousing ones, unlike healthy individuals.

Despite having similar emotional reactions to odors, the MTLR patients lost the specific memory advantage typically associated with strong emotional responses, indicating the critical role of the amygdala in odor memory related to emotional arousal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medial temporal-lobe damage and memory for emotionally arousing odors. Pouliot, S., Jones-Gotman, M.[2016]

Individuals with anosmia (loss of smell) showed reduced gray matter volumes in brain regions associated with emotional processing, specifically the hippocampus-amygdala and precuneus networks, compared to controls.

Lower gray matter volumes in the hippocampus-amygdala network were linked to poorer olfactory-specific quality of life and higher levels of depressive symptoms, indicating a potential relationship between olfactory loss and emotional health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gray matter volume reduction in the emotional brain networks in adults with anosmia. Lee, S., Kim, J., Kim, BJ., et al.[2022]

In a study involving healthy subjects exposed to aversive olfactory stimuli, significant increases in regional cerebral blood flow (rCBF) were observed in both amygdalae and the left orbitofrontal cortex when exposed to highly aversive odors, indicating their role in emotional processing.

The left amygdala's activity was closely linked to how aversive the subjects found the odors, suggesting that the amygdala is crucial for processing the emotional aspects of smells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation. Zald, DH., Pardo, JV.[2022]

The amygdala's response to chemosensory stimuli varies based on the pleasantness of the odor, with pleasant smells activating the left amygdala and unpleasant smells activating the right amygdala, highlighting the amygdala's role in emotional processing.

Chemosensory stimuli also activate a network of brain regions, including the orbitofrontal cortex and insula, indicating that the amygdala works closely with these areas to process olfactory information and emotional responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human amygdala activations during nasal chemoreception. Patin, A., Pause, BM.[2015]

The amygdala influences olfactory processing by modulating norepinephrine release from the locus coeruleus, which affects how sensory signals are selected for processing in the brain.

Inactivating the amygdala strengthened the response to weak olfactory inputs, suggesting a mechanism of sensory gating that could be relevant for understanding sensory dysfunctions in affective disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amygdalar Gating of Early Sensory Processing through Interactions with Locus Coeruleus. Fast, CD., McGann, JP.[2018]

In a study involving 16 male combat veterans (8 with PTSD and 8 without), exposure to the smell of diesel, which is linked to traumatic memories, triggered significant emotional distress and increased PTSD symptoms in those with PTSD, highlighting the strong connection between odors and emotional memories.

PET imaging revealed that PTSD patients had increased blood flow in brain areas associated with emotion and memory processing, such as the amygdala and medial prefrontal cortex, when exposed to trauma-related smells, indicating a unique neural response compared to veterans without PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron tomographic emission study of olfactory induced emotional recall in veterans with and without combat-related posttraumatic stress disorder. Vermetten, E., Schmahl, C., Southwick, SM., et al.[2023]

Bilateral lesions of the amygdala in newborn rats significantly blocked their ability to form odor preferences after classical conditioning, indicating the amygdala's crucial role in early olfactory learning.

Interestingly, the effects of amygdala lesions could be reversed with extensive overtraining, suggesting that while the amygdala is important for initial learning, other mechanisms may compensate with enough practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of the amygdala complex in early olfactory associative learning. Sullivan, RM., Wilson, DA.[2019]

Using optogenetic methods, the study found that stimulation of the basolateral amygdala (BLA) significantly modulates odor-evoked activity in the posterior piriform cortex (pPCX), indicating that the BLA plays a crucial role in how odors are processed in the brain.

The BLA's influence on pPCX activity can lead to changes in how odors are perceived and responded to, suggesting that this interaction may be important for learning and adapting responses to different odors based on context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optogenetic Stimulation of Lateral Amygdala Input to Posterior Piriform Cortex Modulates Single-Unit and Ensemble Odor Processing. Sadrian, B., Wilson, DA.[2018]

The study reveals that the posteromedial cortical nucleus (PmCo) of the amygdala plays a crucial role in modulating the olfactory bulb's response to odors by inhibiting mitral cells through GABAergic granule cells.

Optogenetic activation of the PmCo enhances the sensitivity of mitral cells to olfactory stimuli, suggesting that this feedback circuit is important for processing social and primary olfactory information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amygdala Corticofugal Input Shapes Mitral Cell Responses in the Accessory Olfactory Bulb. Oboti, L., Russo, E., Tran, T., et al.[2020]

Anxiety can significantly alter how we perceive smells, making neutral odors seem unpleasant and harder to detect, as shown in an fMRI study that examined the brain activity of human subjects after anxiety induction.

The study revealed that anxiety strengthens connections between the amygdala and olfactory processing areas in the brain, suggesting that emotional states can deeply influence our sense of smell, which may contribute to emotional disorders like anxiety and depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When the sense of smell meets emotion: anxiety-state-dependent olfactory processing and neural circuitry adaptation. Krusemark, EA., Novak, LR., Gitelman, DR., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Human Primary Olfactory Amygdala Subregions Form Distinct Functional Networks, Suggesting Distinct Olfactory Functions. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A specific role for the human amygdala in olfactory memory. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Medial temporal-lobe damage and memory for emotionally arousing odors. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Gray matter volume reduction in the emotional brain networks in adults with anosmia. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Human amygdala activations during nasal chemoreception. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Amygdalar Gating of Early Sensory Processing through Interactions with Locus Coeruleus. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Positron tomographic emission study of olfactory induced emotional recall in veterans with and without combat-related posttraumatic stress disorder. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Role of the amygdala complex in early olfactory associative learning. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Optogenetic Stimulation of Lateral Amygdala Input to Posterior Piriform Cortex Modulates Single-Unit and Ensemble Odor Processing. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Amygdala Corticofugal Input Shapes Mitral Cell Responses in the Accessory Olfactory Bulb. [2020]

12. United States pubmed.ncbi.nlm.nih.gov

When the sense of smell meets emotion: anxiety-state-dependent olfactory processing and neural circuitry adaptation. [2022]