Hello, my name is Nicholas Sedario and I'm a second year medical student at Rutgers Robert Wood Johnson Medical School And today I'll be presenting a connectivity model underlying Gerstmann syndrome, and this was done under the supervision and mentorship of Dr. Michael Shugrue. I have no disclaimers related to the current project Gerstmann syndrome is a constellation of diverse neurologic deficits. It includes agraphia, acalculia, left-right disorientation, and finger agnosia. First described by Gerstmann himself, an Austrian-born neurologist who later moved to the United States, he described the first case in 1924 and an additional few cases soon right after that. Based on the experience of these cases, he argued for the idea of a Grunstraum, which basically says there's a common denominator underlying these four diverse neurologic deficits. That idea appealed to a lot of people at the time because, you know, the idea to reduce four different diverse cognitive domains into a single shared neuroanatomic substrate, in addition to the obvious lesion localization of values to something like that, before the advent of advanced neuroimaging techniques, this was really an intellectually stimulating idea. And there was a lot of debate on this, both for as well as against this idea, and one of the difficulties studying it is that these cases were reported, they were rare, they were in isolation, they reported regions mostly through the left parietal lobe, the dominant parietal lobe, as well as also the frontal lobe. However, generally there's consensus in the literature that damage to the left parietal lobe can cause this. However, you know, that's very vague and there's no clinical benefit of something like that. The best evidence comes from electrical stimulation studies in awake brain surgery, and that points towards a supermarginal gyrus, but that too has failed to conclude and find a specific region or anatomic substrate that can cause all four Gerstmann symptoms together. With the increase in neuroimaging abilities and now non-invasive brain mapping, we've seen a resurface of interest in this topic, especially trying to investigate if this is a cortical or subcortical disconnection syndrome. However, still, despite these increases in advances in techniques, we still have no definitive answer on what can cause this syndrome. To combat the rarity of this case in the literature and how it's reported in isolation, we utilized meta-analytic methodology to basically try to find a shared neuroanatomic substrate for Gerstmann syndrome across the multiple neuroimaging studies that have been reported. So using electronic databases like BrainMap-Sleuth and PubMed Medline, we did a literature search for fMRI and PET studies related to the four symptoms of Gerstmann syndrome. We aggregated the reported regions from these studies and utilized ginger ale to generate an activation likelihood estimation map, which is an ale. And basically, so as you can see in the left-hand corner, we created the ales for all four symptoms. One row would be agraphia, another row would be acalculia, another row would be left-right disorientation, and so on. And for each of these ales, we then used machine learning and artificial intelligence to try to map it to the human connectome project parcellation scheme, which is a very fine and precise established parcellation scheme that can allow us to have a more specific localization of our possible neuroanatomic substrate. So we did this for each each symptom, and then we use structural tractography on healthy individuals, 25 healthy individuals also from the human connectome project, so that we can understand the structural interconnectedness of a cortical model for each of these symptoms. So for instance, our model for writing would be after using the writing ale, matching it to the HCP atlas, and then performing tractography. When looking at our functional and structural results for each symptom, we see that a frontal parietal network is found to be involved in all four cognitive domains regarding calculation, writing, finger gnosis, and left-right orientation. And this implicated, as expected, numerous brain networks in agreement with the literature, such as the multiple demand network, a sensory motor cluster, as well as dorsal attention network. And you know, in agreement with previous hypotheses regarding a disconnection's possible origin of the syndrome, we did find that these regions contributed to a similar white matter bundle, namely the superior longitudinal fasciculus, which for our sake will include the arcuate fasciculus as well. But this region is, you know, it's the largest white matter bundle in the cerebrum. It's in both hemispheres, and it's known for its connections in the prairie sylvian area, the parietal, and occipital cortices. While this bundle is mostly known for speech and language, it's also been described to contribute to attention and visuospatial processing and cognition. And this is in agreement with the possible symptomology of Gerstmann syndrome, and has been proposed for the basic Gerstmann syndrome previously, but not enough detail. While our cortical model implicated a lot of diverse regions for each of the symptoms, generally, we did find shared regions amongst all four domains. So the regions that were shared were area 7 PC, as well as the lateral intraparietal areas MIP and AIP, which is medial intraparietal and anterior intraparietal, which generally, the human connectome project groups the superior parietal ovulence of 10 regions of interest, which includes these three. If we look at area AIP, this is on the superior bank of the intraparietal sulcus, specifically at its most anterior aspect. If you look at the its most anterior superior border of AIP, that's area 7 PC. And if we look at area MIP, that's the posterior portion of the superior bank of the intraparietal sulcus. You can see different cuts on the image shown right now. Importantly, you know, for this presentation, we decided to say Gerstmann syndrome was at least three of the four cognitive domains. If it was shared at least three of the four, then we wanted to consider that the Gerstmann core, and this was the idea of hoping to capture the most underlying commonality in neurobehavioral domains across the largest amount of data currently available in the literature. While, you know, there's a lot of debate on how many symptoms are in Gerstmann syndrome truly, if there's any additional more than four or less than four, and there is a lot of literature that supports the idea that at least three or four symptoms has lesion localizational value, even if we were to make our definition stricter, area 7 PC still was common amongst all four cognitive domains, which is not shown previously, and this was an extremely interconnected region throughout our cortical models, especially through the SLF. So what does this basically show us moving forward? This shows us that additionally to finding a functionally connected region between these different functional domains, there are also shared common fiber tracts that may support previous hypotheses that Gerstmann is caused by cortical-subcortical disconnections, especially near the anteromedial portion of the intraparietal sulcus. So, you know, why is that important? Well, this kind of brings home the point about the important benefits of connectomic data, as well as tractography in general in the perioperative period, basically provides us a precise anatomic map that allows us during surgery to avoid damage to specific cortical structures and white matter connections that can cause syndromes like Gerstmann syndrome. So a good way to think of this is like being in the ocean and seeing these navigational posts that tells us, you know, where to avoid and where to cut. And this is important because while this current study focused on using our methodology to understand Gerstmann syndrome, obviously this can be applied to similar other syndromes like SMA syndrome, as well as other medial frontal lobe syndromes, and etc., because it provides us data that we can use tangibly during surgery, as well as understand the risks and benefits of different surgical decisions and the deficits associated with certain syndromes and why they're actually occurring. These are our references, and thank you for coming to our presentation.

Nicholas Sedario

Gerstmann syndrome

neurologic deficits

connectivity model

Josef Gerstmann