Summary of “Brain Volume Changes in Hyposmic Patients Before and After Olfactory Training”

Olfactory dysfunction, particularly following upper respiratory tract infections (URTI), is a common condition associated with reduced gray matter (GM) volume in olfactory-related brain regions. This study by Gellrich et al. aimed to determine whether olfactory training (OT) could induce structural brain changes and improve olfactory function in patients with smell loss due to URTI.

Study Design and Methodology

This prospective intervention case-control study included 30 hyposmic patients (with post-URTI olfactory dysfunction) and 31 healthy controls. The patients underwent 12 weeks of olfactory training, exposing themselves to four distinct odors (rose, eucalyptus, lemon, cloves) twice daily.

• Olfactory function was assessed before and after training using the Sniffin’ Sticks test, which measures threshold (T), discrimination (D), and identification (I) abilities.

• Magnetic resonance imaging (MRI) was used to evaluate brain volume changes, employing voxel-based morphometry (VBM) to assess gray matter volume in olfactory-related brain areas.

• Olfactory bulb (OB) volume was also measured, as it is known to correlate with olfactory function.

Key Findings

1. Olfactory Training Improved Olfactory Function

• Patients significantly improved their TDI scores (threshold, discrimination, and identification) after OT.

• More than 50% of patients (16 out of 30) showed clinically significant improvement, with a TDI increase of 5.5 points or more.

• Despite this, patients did not fully recover to the level of the control group, indicating partial but meaningful restoration of smell function.

2. Brain Volume Increased in Key Cognitive Areas After OT

• Before training, patients had reduced gray matter volume in the hippocampus and thalamus compared to controls.

• After OT, patients exhibited significant increases in GM volume in these areas, particularly in:

• Hippocampus (a key region for memory and learning)

• Thalamus (involved in sensory processing and olfactory attention)

• Cerebellum (which plays a role in motor control and sensory integration)

• The olfactory bulb (OB) volume did not significantly change, although a trend of increased volume was observed after OT.

3. No Structural Changes in Primary Olfactory Regions

• Unlike previous studies that linked olfactory dysfunction to reduced primary olfactory cortex volume, this study found no significant differences in primary olfactory-related regions between patients and controls.

• This suggests that olfactory training primarily influences higher-order cognitive and sensory integration areas (hippocampus, thalamus) rather than the olfactory cortex itself.

Neuroscientific and Clinical Implications

1. Hippocampal Plasticity and Olfactory Memory

• The hippocampus is essential for memory formation, including olfactory-related memories.

• The increase in hippocampal GM volume suggests that OT may enhance odor-related cognitive processing, supporting the idea that smell and memory are closely linked.

2. Thalamic Involvement in Olfactory Attention

• The thalamus modulates attention and sensory processing, including olfaction.

• The increase in thalamic volume after OT may indicate enhanced attentional processing of odors, suggesting that actively engaging with smells can rewire sensory pathways.

3. Olfactory Bulb and Plasticity

• While olfactory bulb volume correlates with olfactory function, this study found only a weak trend toward OB growth after OT.

• This suggests that olfactory improvements following training may be more related to cognitive and sensory integration rather than direct structural changes in the OB.

Limitations and Future Research Directions

While the study provides strong evidence for olfactory training-induced neuroplasticity, it has some limitations:

• The training duration was only 12 weeks—recent studies suggest that 36 weeks of OT may lead to greater improvements.

• Compliance with OT was not closely monitored—future studies should track adherence to training protocols.

• The sample size was relatively small, making it difficult to generalize findings to broader populations.

• The study did not measure functional connectivity—future research could use functional MRI (fMRI) to explore how OT affects neural networks involved in olfaction and cognition.

Conclusion

This study demonstrates that olfactory training can improve smell function and induce structural brain changes, particularly in the hippocampus and thalamus. These findings suggest that OT is not just a peripheral sensory intervention but also engages cognitive and memory-related brain areas. The study supports the use of OT as a non-invasive therapy for olfactory dysfunction and potentially for cognitive enhancement in aging and neurodegenerative conditions.