frontal thalamus done!

Author: rcoreilly

content/media/fig_thalamus_frontal_alonso_martinez_etal_23.png

@@ -122,12 +122,20 @@ There are three major functions for thalamic areas interconnected with frontal a
 
 ### Rodent
 
-{id="figure_prjn-kuramoto" style="height:25em"}
-![Summary of projections from the different ventral motor thalamic areas in rodents, where VM is the rodent version of VA, and VAmc does not exist. VL can be defined as the specific subset of neurons receiving cerebellar nucleus (CN) driver inputs (inluding caudodorsal VA), which have focal core-like projections as shown on the right. The VM neurons (which include rostroventral VA), consistent with VA and VAmc in macaque, receive extensive BG output (SNr, GPi) and project in a more diffuse matrix-like pattern to superficial layers. From Kuramoto et al., 2015.](media/fig_thalamus_prjn_vm_vl_kuramoto_etal_15.png)
+{id="figure_frontal-alonso" style="height:45em"}
+![Summary of inputs to the ventral anterior thalamic nuclei that interconnect with the frontal cortex, in rodent (mouse) and macaque (primate). The highlighted labels in the middle provide an alternative to the inconsistently-used anatomical labels, based definitionally on the source of the driver inputs: VAgpi is the part of VM/VA that receives from GPi, while VAsnr receives from SNr. The VL in rodent can be clearly defined as the area receiving strong driver inputs from DCN (deep cerebellar nuclei). The macaque data is schematic from older sources. VAmc is the medial portion of VA as shown, which only exists in primate, and is defined by its projections into the PFC, whereas VAgpi and VAsnr correspond with the rodent versions, which only project to motor areas. VLp is the DCN recipient area, which we will label VLcn for clarity. From Alonso-Martinez et al., 2023.](media/fig_thalamus_frontal_alonso_martinez_etal_23.png)
+
+We begin with the simpler case of the rodent, which has each of these different functions clearly represented by different thalamic nuclei. The primate case then adds more complexity that can be understood as building upon this same basic foundation. [[#figure_frontal-alonso]] shows the organization of BG (SNr, GPi) vs. cerebellar (CN) driver inputs for the ventral anterior thalamic nuclei that project to the frontal cortex ([[@Alonso-MartinezRubio-TevesCasas-TorremochaEtAl23]]). Because the anatomical terminology for these thalamic areas is inconsistent across papers and across species, we define the following labels that will be used in the remainder of our discussion:
+
+* VAgpi is the VM/VA/VL area that receives inhibitory inputs from GPi (entopeduncular or ENT in rodent), which projects to motor cortex (but not PFC).
+* VAsnr is the VM/VA area that receives inhibitory inputs from SNr and projects to motor cortex, but not PFC.
+* VAmc is the subset of VA in primate that has magnocellular cells, which projects to PFC and receives from SNr (does not exist in rodent).
+* VLcn is the VL area that receives excitatory driver inputs from CN (cerebellar nuclei).
 
-We begin with the simpler case of the rodent, which has each of these different functions clearly represented by different thalamic nuclei. The primate case then adds more complexity that can be understood as building upon this same basic foundation.
+{id="figure_prjn-kuramoto" style="height:25em"}
+![Summary of projections from the different ventral motor thalamic areas in rodents. VL in the EZ = excitatory zone is thus the VLcn that receives cerebellar nucleus (CN) driver inputs (which includes caudodorsal VA in rodent), and sends focal core-like projections as shown on the right. The VM neurons (which include rostroventral VA, in the IZ = inhibitory zone) represents VAsnr and VAgpi in our terminology, because it receives extensive BG output (SNr, GPi) and projects in a more diffuse matrix-like pattern to superficial layers. From Kuramoto et al., 2015.](media/fig_thalamus_prjn_vm_vl_kuramoto_etal_15.png)
 
-[[#figure_prjn-kuramoto]] (from [[@KuramotoOhnoFurutaEtAl15]]) shows two ventral thalamic pathways in rodents, which can be identified according to their driver inputs, which correspond roughly to corresponding areas in the macaque monkey: VL, and VM. VL (which also includes caudodorsal VA) receives strong drivers from the cerebellar nuclei, and projects focally to middle lamina in motor areas (i.e., core-like), enabling motor areas to learn the language of the spinal cord. VM (which also includes rostroventral VA) receives BG disinhibitory outputs (SNr, GPi), and projects to superficial lamina in a widely-branching manner (i.e., matrix-like), and allows BG to send a broad gating signal to all of motor cortex. 
+[[#figure_prjn-kuramoto]] (from [[@KuramotoOhnoFurutaEtAl15]]) shows ventral thalamic pathways in rodents, which can be identified according to their driver inputs, per our standard labels abovel. VLcn (which also includes caudodorsal VA; [[@Alonso-MartinezRubio-TevesCasas-TorremochaEtAl23]]) receives strong drivers from the cerebellar nuclei, and projects focally to middle lamina in motor areas (i.e., core-like), enabling motor areas to learn the language of the spinal cord. VAgpi and VAsnr (which also includes rostroventral VA; [[@Alonso-MartinezRubio-TevesCasas-TorremochaEtAl23]]) receives BG disinhibitory outputs (SNr, GPi), and projects to superficial lamina in a widely-branching manner (i.e., matrix-like), and allows BG to send a broad gating signal to all of motor cortex. This signal could be important for driving the cortical system from motor preparation to motor execution.
 
 {id="figure_md-pfc" style="height:20em"}
 ![Thalamocortical connectivity for different regions of the MD thalamus in rats. MDm (medial) is the main goal-driven gating area, which receives disinhibitory input from ventral pallidum (VP), and projects to the core goal areas (IL, PL, and OFC areas). MDc (central) projects to more OFC areas and may be important for updating during goal approach. MDl (lateral) targets the complementary ACC and PL goal areas, along with motor plan areas in (FrA = frontal association higher level motor, M2 = secondary motor). From Kuramoto et al., 2017.](media/fig_md_pfc_conns_kuramoto_etal_17.png)
@@ -139,41 +147,44 @@ These MD areas also have non BG-gated neurons that putatively receive CT inputs
 ### Primate
 
 {id="figure_frontal-areas" style="height:40em"}
-![Thalamic nuclei in macaque monkeys showing the projections received from SNr (BG) as a function of the frontal areas that these cortical areas project to (inset below legend), with A = PSv, ventral of the principal sulcus (e.g., IFG in human PFC); B = dlPFC (areas 9, 46); C = motor areas (M1, SMA, PMd). VAmc projects widely to all PFC areas, and has significant SNr input, while MDpc and MDmf mainly interconect with the PSv area associated with caudal SNr inputs. AM = anteromedial. Note that MD has a mix of neurons with no SNr input (typically with cortical drivers, like pulvinar), and those with SNr or VP (ventral pallidum, for MDmc) inputs. From Tanibuchi et al., 2009.](media/fig_thalamus_frontal_tanibuchi_etal_09.png)
+![Thalamic nuclei in macaque monkeys showing the projections received from SNr (BG) as a function of the frontal areas that these cortical areas project to (inset below legend), with A = PSv, ventral of the principal sulcus (e.g., IFG in human PFC); B = dlPFC (areas 9, 46); C = motor areas (M1, SMA, PMd). VAmc projects widely to all PFC areas, and has significant SNr input. VApc corresponds to VAsnr in our terminology, and projects only to motor areas. MDpc and MDmf mainly interconect with the PSv area associated with caudal SNr inputs. AM = anteromedial. Note that MD has a mix of neurons with no SNr input (typically with cortical drivers, like pulvinar), and those with SNr or VP (ventral pallidum, for MDmc) inputs. From Tanibuchi et al., 2009.](media/fig_thalamus_frontal_tanibuchi_etal_09.png)
 
-[[#figure_frontal-areas]] shows the anatomical organization of the frontal thalamic areas in the macaque monkey, including the different subdivisions of the MD (where the rodent MDm = MDmc, MDc = MDpc, and MDl = MDmf, MDdc), VL (including VLm and VLo, defined functionally as neurons receiving driver inputs from cerebellar nuclei), and VA, which is functionally divided into a specialized VAmc found only in primates, versus the rest of VA that resembles VM in rodents.
+[[#figure_frontal-areas]] shows the anatomical organization of the frontal thalamic areas in the macaque monkey, including the different subdivisions of the MD (where the rodent MDm = MDmc, MDc = MDpc, and MDl = MDmf, MDdc), VLcn (including VLm and VLo, defined functionally as neurons receiving driver inputs from cerebellar nuclei), and the primate-specific VAmc (medial, magnocellular portion of VA) that projects to the PFC, and rodent-like VAgpi, VAsnr in our terminology, which project only to motor areas, and maps onto VApc and portions of LVo in this primate terminology. 
 
 {id="figure_phillips-cons" style="height:40em"}
 ![Similarity of patterns of MD thalamic connectivity with prefrontal cortex (PFC) in the macaque, which typically also reflects direct interconnectivity strength. Red and orange areas are ventral and medial PFC goal-driven areas (i.e, the core of the [[Rubicon]] model), including OFC (13, 14, 11; specific outcomes), IL (25; abstract outcomes), and PL (32; integrated reward-cost utility: note broader interconnectivity, especially with 24, 25 and 9); Yellow (10) is polar frontal cortex, unique to primates, important for episodic memory and outer loops of processing; Green (47,12) is vlPFC (ventrolateral) for control over the temporal lobe (language, objects etc); Cyan (9, 46d, 45a) is dlPFC (dorsolateral) for control over parietal lobe for spatial and temporal organization of action (broad plans); Blue (8) is FEF (frontal eye fields) which has similar connectivity to PM (premotor), SMA (supplementary motor area) and primary motor cortex (M1). Area 24 is ACC (anterior cingulate cortex) which represents the value (mostly costs) of actions, and has very broad interconnectivity with motor areas, but also goal areas, especially 32 (PL). Adapted from Phillips et al., 2019.](media/fig_thalamus_pfc_simat_phillips_etal_19.png)
 
 [[#figure_phillips-cons]] shows the similarity structure of the various PFC areas according to their patterns of MD thalamic connectivity ([[@PhillipsFishKambiEtAl19]]). This identifies the primary functional groupings of goal-driven areas in v/mPFC (OFC, IL, PL), the ACC which bridges motor and these goal-driven areas to represent action value (costs), and the dlPFC and vlPFC that interconnect with posterior cortical areas (parietal and temporal lobes, respectively; [[@OReilly10]]) and guide [[motor]] frontal actions.
 
+{id="figure_frontal-sum" style="height:30em"}
+![Summary of frontal thalamic connectivity and function for the primate case (macaque). MDm (medial) is the goal gating nucleus, receiving from and projecting to all the goal-driven PFC areas (OFC, IL, PL, dACC, dlPFC), with disinhibitory gating from the ventral pallidum (VP). MDc (central) drives dlPFC working memory (WM) gating, via SNr disinhibition. MDl does premotor (PM, SMA areas 8,6) gating. VLcn has cerebellar drivers and projects to M1 to train motor representations to speak the language of the spinal muscle synergies. POm (posterior medial in rodents, medial pulvinar in primates) drives predictive learning in motor cortex from somatosensory (S1) drivers. VAmc and VAbg (VAsnr, VAgpi) have broad convergent inputs from respective frontal areas, and project matrix-style modulator outputs to layer1 across a broad range of areas (PFC for VAmc, motor areas for VAbg). This is likely important for synchronizing these areas at major points of transition, e.g., between planning and execution of actions.](media/fig_thalamus_frontal_connectivity.png)
+
 {id="table_frontal-thal" title="Frontal thalamus areas"}
 | Area        | Function     | Drivers          | Modulators        | BG   | Strong outs    | Weak outs | Lamina   | Other ins            | Other outs |
 |-------------|--------------|------------------|-------------------|------|----------------|-----------|----------|----------------------|------------|
 | **Learning**|              |                  |                   |      |                |           |          |                      |            |
 | PULm / POm  | S1->M1 Learn | S1, Spinal       | M1, M2            | --   | M1, M2, SMA..  |           | Mid      | spinal somatosensory |            |
-| VL          | CN->M1,M2 Learn | CN            | M1,M2             | --   | M1, M2         |           | Mid      | CN                   |            | 
+| VLcn        | CN->M1,M2 Learn | CN            | M1,M2             | --   | M1, M2         |           | Mid      | CN                   |            | 
 | MD          | Predictive learning | (see below) |                 | --   |                |           |          |                      |            |
 | **Gating**  |  **(focal)** |                  |                   |      |                |           |          |                      |            |
 | AM          | MTL <-> goal | ACC, OFC, IL, PL | d/vlPFC, lOFC     | mGPi | 10, 11, 12, 46 | PL, ACC   | Mid      | CA3, aSub, BLA, mGPi | vSub, RSC  |
 | MDm (mc)    | goal engage  | OFC, IL, PL      | vlPFC, ACC        | VP   | OFC            | PL, IL    | S/D, Mid | IT polar, EC, PRh, Sub, BLA |     |
 | MDc (pc)    | dl/plan WM   | 10, dlPFC        | ACC, PL, PM, SMA  | SNr  | dlPFC (WM)     | PM, SMA   | Mid      | parietal             | parietal   |
 | MDl (mf,dc) | eye/act motor| 8 (FEF), PM, SMA |                   | SNr  | 8, PM, SMA     |           | Mid      | SC, parietal attn    |            |
 | **Gating**  | **(diffuse)** |                 |                   |      |                |           |          |                      |            |
-| VA          | BG->motor    |                  |                   | GPi  | M1, M2, SMA, DM|           |          |                      |            |
-| VAmc / VM   | BG->dl/motor | dl, PL, ACC      |                   | SNr  | dlPFC, M2, M1  |           | Mid + S/D| parietal, temp pole  | parietal   |
+| VAgpi, VAsnr | BG->motor   |                  |                   | GPi, SNr | M1, M2, SMA, DM|       |          |                      |            |
+| VAmc        | BG->dl/motor | dl, PL, ACC      |                   | SNr  | dlPFC, M2, M1  |           | Mid + S/D| parietal, temp pole  | parietal   |
 
-[[#table_frontal-thal]] provides an overall summary of all motor thalamus areas in primate and rodent, organized according to the three primary functions listed above, based on all the available data ([[@PhillipsKambiRedinbaughEtAl21]]; [[@TimbieBarbas15]]; [[@XiaoZikopoulosBarbas09]]). Note the dual-functionality of area MD, for pulvinar-like predictive learning and BG-driven gating / updating. The role of the AM in interconnecting the medial temporal lobe including the [[hippocampus]], subiculum, and the retrosplenial cortex (RSC) in the medial parietal lobe is critical for enabling episodic memories to be engaged in the service of goal planning, as is discussed a bit further in the section on [[#anterior thalamic areas]] (see also [[@XiaoZikopoulosBarbas09]]).
+[[#figure_frontal-sum]] and [[#table_frontal-thal]] provide an overall summary of all motor thalamus areas in primate and rodent, organized according to the three primary functions listed above, based on all the available data ([[@PhillipsKambiRedinbaughEtAl21]]; [[@TimbieBarbas15]]; [[@XiaoZikopoulosBarbas09]]). Note the dual-functionality of area MD, for pulvinar-like predictive learning and BG-driven gating / updating. The role of the AM in interconnecting the medial temporal lobe including the [[hippocampus]], subiculum, and the retrosplenial cortex (RSC) in the medial parietal lobe is critical for enabling episodic memories to be engaged in the service of goal planning, as is discussed a bit further in the section on [[#anterior thalamic areas]] (see also [[@XiaoZikopoulosBarbas09]]).
 
 The function of the MDc in primates has been expanded relative to the rodent case (where it primarily targets OFC), to include a significant role in updating working memory representations in the dorsal and ventral lateral areas (dlPFC, vlPFC) ([[@FunahashiBruceGoldman-Rakic89]]; [[@FusterAlexander73]]; [[@TakedaFunahashi02]]), consistent with the [[PBWM]] (prefrontal cortex, basal ganglia working memory) model. It is likely that different neurons target different areas within the large expanse of MDc, so the rodent-specific case is likely still supported by a subset of these neurons. Likewise, MDl in primates includes a more significant role for saccade-based updates of motor representations, driven by strong FEF 8a driver inputs, which could then drive broader motor gating.
 
 The other major new element in the primate thalamus is the VAmc, which is the magnocellular compartment of the ventral anterior thalamus ([[@PhillipsKambiRedinbaughEtAl21]]). This area has very broad overlapping inputs, with virtually no topographic organization of input projections, which come from all over the PFC, and project back broadly to the PFC and to motor cortex. Consistent with this broad diffuse connectivity, it sends matrix-like layer I outputs, but also projections to middle lamina. Interestingly, the layer 6 CT inputs to VAmc target the PV expressing neurons that project to the middle layers of cortex (core-style), while the layer 5 inputs arise from layer 5a neurons that target CB expressing neurons, which give rise to the layer 1 superficial and some deep layer projections (matrix-style).
 
-The broad connectivity of this area seems ideally suited for _coordinating_ processing across the frontal motor and PFC areas according to major motor-based events, such as saccades or large-scale body movements. There are generally abrupt transitions in cortical states at the onset of motor actions, and these broad, diffuse connections could effectively broadcast signals that facilitate these transitions, enabling the system to transition between preparatory activity and actual motor action ([[@ChurchlandShenoy24]]; [[@EconomoViswanathanTasicEtAl18]]).
+The broad connectivity of VAmc, similar to that of VAgpi and VAsnr, seems ideally suited for _coordinating_ processing across the frontal motor and PFC areas according to major motor-based events, such as saccades or large-scale body movements. There are generally abrupt transitions in cortical states at the onset of motor actions, and these broad, diffuse connections could effectively broadcast signals that facilitate these transitions, enabling the system to transition between preparatory activity and actual motor action ([[@ChurchlandShenoy24]]; [[@EconomoViswanathanTasicEtAl18]]).
 
 <!--- * AM, MD get significant CT layer 6 inputs (only 20% layer 5 drivers), whereas VL,VA,VAmc all have nearly 50% layer 5 inputs ([[@XiaoZikopoulosBarbas09]]).  PT layer 5b (deep) ([[@XiaoZikopoulosBarbas09]]) are more focal, whereas 5b (superficial, IT) are broader -->
-    
+
 ## Anterior thalamic areas
 
 [[@AggletonOMara22]] -- key ref.