Table 3.
fMRI BOLD response for idalopirdine plus donepezil compared to vehicle following a single administration.
| Vehicle vs. Donepezil and Idalopiridine, positive BOLD volume of activity | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 15–25 min post-treatment | 25–35 min post-treatment | 35–45 min post-treatment | |||||||||
| Brain area | Veh | I/D | P-val | Brain area | Veh | I/D | P-val | Brain area | Veh | I/D | P-val |
| Magnocellular preoptic nucleus | 0 | 2 | 0.012 | Infralimbic ctx | 0 | 39 | 0.006 | Infralimbic ctx | 0 | 28 | 0.002 |
| Medial preoptic area | 0 | 25 | 0.014 | Granular cell layer | 15 | 81 | 0.006 | Medial orbital ctx | 0 | 21 | 0.007 |
| Medial amygdaloid nucleus | 2 | 12 | 0.014 | Accumbens shell | 0 | 13 | 0.006 | Triangular septal nucleus | 3 | 10 | 0.011 |
| Ventral pallidum | 0 | 15 | 0.018 | Anterior olfactory nucleus | 0 | 33 | 0.007 | Anterior olfactory nucleus | 1 | 32 | 0.014 |
| Median raphe nucleus | 0 | 4 | 0.018 | Lateral preoptic area | 0 | 8 | 0.008 | Accumbens shell | 0 | 15 | 0.016 |
| Anterior olfactory nucleus | 0 | 32 | 0.019 | Habenula nucleus | 3 | 18 | 0.009 | Entorhinal ctx | 51 | 168 | 0.017 |
| Ventral tegmental area | 0 | 4 | 0.03 | Ventral pallidum | 0 | 5 | 0.009 | Ventral pallidum | 0 | 4 | 0.018 |
| Posterior hypothalamic area | 0 | 12 | 0.03 | Triangular septal nucleus | 0 | 9 | 0.012 | Granular cell layer | 36 | 75 | 0.019 |
| Medial dorsal thalamic nucleus | 0 | 9 | 0.031 | Medial preoptic area | 0 | 26 | 0.012 | Medial preoptic area | 1 | 22 | 0.022 |
| Pedunculopontine tegmental area | 0 | 4 | 0.033 | 3rd cerebellar lobule | 4 | 22 | 0.013 | Tenia tecta ctx | 6 | 42 | 0.023 |
| Infralimbic ctx | 0 | 19 | 0.033 | Lateral posterior thalamic nucleus | 8 | 45 | 0.013 | Prelimbic ctx | 5 | 12 | 0.026 |
| Ventromedial thalamic nucleus | 0 | 11 | 0.033 | Periaqueductal gray thalamus | 9 | 75 | 0.013 | Medial pretectal area | 0 | 0 | 0.028 |
| Granular cell layer | 22 | 85 | 0.034 | Accumbens core | 0 | 2 | 0.013 | Lateral preoptic area | 0 | 6 | 0.034 |
| Accumbens shell | 0 | 12 | 0.034 | Medial dorsal thalamic nucleus | 2 | 11 | 0.019 | Anterior cingulate area | 12 | 59 | 0.034 |
| Triangular septal nucleus | 1 | 5 | 0.034 | Dentate gyrus ventral | 4 | 24 | 0.019 | Lateral septal nucleus | 16 | 40 | 0.034 |
| Tenia tecta ctx | 6 | 46 | 0.034 | Prelimbic ctx | 1 | 18 | 0.023 | Magnocellular preoptic nucleus | 0 | 2 | 0.035 |
| Cortical amygdaloid nucleus | 11 | 26 | 0.037 | Lateral septal nucleus | 16 | 45 | 0.024 | Accumbens core | 0 | 2 | 0.039 |
| Diagonal band of broca | 0 | 4 | 0.038 | Bed nucleus stria terminalis | 2 | 14 | 0.026 | Anterior hypothalamic area | 2 | 10 | 0.049 |
| Lateral preoptic area | 0 | 7 | 0.039 | Diagonal band of Broca | 0 | 7 | 0.026 | Primary somatosensory ctx hindlimb | 5 | 24 | 0.051 |
| 3rd cerebellar lobule | 2 | 7 | 0.04 | Medial pretectal area | 0 | 0 | 0.028 | Anterior pretectal nucleus | 9 | 19 | 0.051 |
| Medial orbital ctx | 0 | 15 | 0.042 | Tenia tecta ctx | 8 | 47 | 0.029 | Habenula nucleus | 4 | 21 | 0.051 |
| Medial septum | 0 | 1 | 0.044 | Posterior hypothalamic area | 0 | 18 | 0.03 | Lateral posterior thalamic nucleus | 23 | 39 | 0.052 |
| Reuniens nucleus | 0 | 2 | 0.044 | Anterior cingulate area | 4 | 50 | 0.03 | Ventral subiculum | 19 | 50 | 0.052 |
| Central medial thalamic nucleus | 0 | 1 | 0.052 | Secondary somatosensory ctx | 4 | 35 | 0.032 | Posterior hypothalamic area | 2 | 15 | 0.053 |
| Raphe linear | 0 | 1 | 0.052 | Frontal association ctx | 0 | 7 | 0.032 | 3rd cerebellar lobule | 7 | 15 | 0.057 |
| Dorsal raphe | 0 | 4 | 0.052 | Reuniens nucleus | 0 | 3 | 0.033 | Periaqueductal gray thalamus | 24 | 48 | 0.058 |
| Lateral posterior thalamic nucleus | 2 | 33 | 0.057 | Primary somatosensory ctx trunk | 0 | 10 | 0.033 | Diagonal band of Broca | 0 | 7 | 0.063 |
| Primary somatosensory ctx trunk | 0 | 10 | 0.058 | Magnocellular preoptic nucleus | 0 | 1 | 0.035 | Extended amydala | 0 | 2 | 0.063 |
| Zona incerta | 0 | 16 | 0.058 | Central gray | 2 | 7 | 0.037 | Frontal association ctx | 0 | 8 | 0.064 |
| Primary somatosensory ctx upper lip | 0 | 59 | 0.059 | Parafascicular thalamic nucleus | 2 | 21 | 0.037 | Medial dorsal thalamic nucleus | 3 | 10 | 0.069 |
| Dentate gyrus ventral | 1 | 8 | 0.061 | External plexiform layer | 29 | 43 | 0.038 | Medial amygdaloid nucleus | 5 | 14 | 0.069 |
| Anterior hypothalamic area | 0 | 17 | 0.065 | Glomerular layer | 23 | 92 | 0.038 | Dentate gyrus ventral | 5 | 15 | 0.069 |
| Intercalated amygdaloid nucleus | 0 | 0 | 0.067 | Ventromedial thalamic nucleus | 0 | 6 | 0.045 | Ventrolateral thalamic nucleus | 0 | 8 | 0.071 |
| Medial pretectal area | 0 | 0 | 0.067 | Premammillary nucleus | 2 | 4 | 0.048 | Cortical amygdaloid nucleus | 11 | 24 | 0.077 |
| Substantia nigra reticularis | 0 | 24 | 0.072 | Dorsomedial tegmental area | 0 | 5 | 0.05 | Reuniens nucleus | 0 | 3 | 0.081 |
| Premammillary nucleus | 2 | 4 | 0.073 | Primary somatosensory ctx hindlimb | 0 | 43 | 0.05 | Secondary motor ctx | 39 | 53 | 0.084 |
Shown are three sets of results each representing comparisons between vehicle (Veh, n = 9) and idalopirdinen/donepezil (I/D, n = 9) treatment groups at times 15–25 (left), 25–35 (middle), and 35–45 (right) min post treatment. The probability values presented on the far-right column were derived using a Kruskall-Wallis test statistic. Lists were generated to include all areas (out of a total list of 171 areas that comprise the rat MRI atlas) that differed significantly (p < 0.05) for the epoch in which we observed the most changes (i.e., the 25–35 min epoch). Areas are rank-ordered by p-value for visualization. Areas highlighted in bold differed significantly between treatment groups. Areas listed in gray show areas that come closest to threshold for statistical significance.