Danielle Cooke's research while affiliated with Harvard Medical School and other places

Publications (15)

Article
Interhemispheric inhibition (IHI) is a dual-site TMS protocol measuring inhibitory interactions between the primary motor cortices (M1). IHI is performed by applying an initial conditioning stimulus followed by a test stimulus to the contralateral M1. Conventionally, the response in the contralateral hand to the conditioning TMS pulse is either not...
Article
Objective: Treatment of different depression symptoms may require different brain stimulation targets with different underlying brain circuits. The authors sought to identify such targets, which could improve the efficacy of therapeutic brain stimulation and facilitate personalized therapy. Methods: The authors retrospectively analyzed two indep...
Article
Inconsistent findings from migraine neuroimaging studies have limited attempts to localize migraine symptomatology. Novel brain network mapping techniques offer a new approach for linking neuroimaging findings to a common neuroanatomical substrate and localizing therapeutic targets. In this study, we attempted to determine whether neuroanatomically...
Article
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Brain lesions can provide unique insight into the neuroanatomical substrate of human consciousness. For example, brainstem lesions causing coma map to a specific region of the tegmentum. Whether specific lesion locations outside the brainstem are associated with loss of consciousness (LOC) remains unclear. Here, we investigate the topography of cor...
Article
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Human memory is thought to depend on a circuit of connected brain regions, but this hypothesis has not been directly tested. We derive a human memory circuit using 53 case reports of strokes causing amnesia and a map of the human connectome (n = 1000). This circuit is reproducible across discovery (n = 27) and replication (n = 26) cohorts and speci...
Article
Background: Focal brain lesions can lend insight into the causal neuroanatomical substrate of depression in the human brain. However, studies of lesion location have led to inconsistent results. Methods: Five independent datasets with different lesion etiologies and measures of postlesion depression were collated (N = 461). Each 3-dimensional le...
Article
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Cervical dystonia is a neurological disorder characterized by sustained, involuntary movements of the head and neck. Most cases of cervical dystonia are idiopathic, with no obvious cause, yet some cases are acquired, secondary to focal brain lesions. These latter cases are valuable as they establish a causal link between neuroanatomy and resultant...
Article
Full-text available
Objective Recently identified mutations of the axon guidance molecule receptor gene, DCC, present an opportunity to investigate, in living human brain, mechanisms affecting neural connectivity and the basis of mirror movements, involuntary contralateral responses that mirror voluntary unilateral actions. We hypothesized that haploinsufficient DCC+/...
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Functional connectivity with the subgenual cingulate identifies a target in the frontal cortex for transcranial magnetic stimulation. In this issue, Weigand et al. show that proximity of a patient’s stimulation site to this target predicts antidepressant response.
Article
Background The optimal target in the dorsolateral prefrontal cortex (DLPFC) for treating depression with repetitive transcranial magnetic stimulation (rTMS) remains unknown. Better efficacy has been associated with stimulation sites that are 1) more anterior and lateral and 2) more functionally connected to the subgenual cingulate. Here we prospect...

Citations

... Finally, it has been suggested that the existing protocol for investigating interhemispheric interactions could be further optimized (Corp et al. 2021). Interactions between brain areas, as investigated by ds-TMS, are typically expressed as a percentage of the amplitude of conditioned MEPs (CS + TS) divided by the amplitude of single-pulse MEPs (TS only) [i.e., (MEP CS + TS /MEP TS ) * 100]. ...
... Moreover, data coming from transcranial magnetic stimulation studies imply that targeting different regions within the left dorsolateral prefrontal cortex result in a reduction in certain symptoms [55,56]. Other psychiatric disorders which can co-exist with depression include schizophrenia, substance drug abuse, bipolar disorder, post-traumatic stress disorder, and obsessive-compulsive disorder [57,58]. These combinations are usually harder to treat since they involve a cocktail of medications to receive a proper therapeutical response from a patient. ...
... Regardless of the cause of the lesion, its size or precise location, evidence has accumulated in recent years in favor of the connectome hypothesis whereby the specific network(s) affected by the lesion can predict many of the patient's responses through motor, non-motor, cognitive and behavioral domains 1-23 , leading to lesion-driven disconnectivity analyses 24 . A common computational framework was developed recently 2 , and successfully applied to several conditions and pathologies 3,4,6,7,[9][10][11][12][13][14][15][16][17][18]22,25 . Due to the simplicity of this method to correlate behavioral outcomes with the extent of lesion-driven disconnection, the strategy was referred to as lesion network mapping (LNM). ...
... Regardless of the cause of the lesion, its size or precise location, evidence has accumulated in recent years in favor of the connectome hypothesis whereby the specific network(s) affected by the lesion can predict many of the patient's responses through motor, non-motor, cognitive and behavioral domains 1-23 , leading to lesion-driven disconnectivity analyses 24 . A common computational framework was developed recently 2 , and successfully applied to several conditions and pathologies 3,4,6,7,[9][10][11][12][13][14][15][16][17][18]22,25 . Due to the simplicity of this method to correlate behavioral outcomes with the extent of lesion-driven disconnection, the strategy was referred to as lesion network mapping (LNM). ...
... These circuits can be identified using lesion network mapping, a technique that uses a normative connectome database (n = 1,000) to compare the functional connectivity of brain lesions rather than just their location 13 . This technique is traditionally used to study grey matter lesions, as in a recent study of depression associated with focal lesions caused by stroke and penetrating head trauma 6,14 . We found that grey matter lesions that cause depression are functionally connected to a common brain circuit. ...
... We placed 10 mm spheres at published target coordinates for anterior capsulotomy, anterior cingulotomy, subcaudate tractotomy and limbic leucotomy 46 . For each sphere, we calculated the damage score by summing the lesion-circumscribed voxel values on the ALE map and on the transdiagnostic network 106,111 . Significance (P < 0.05) was assessed in Excel by comparing this damage score versus zero (via one-sample t-tests). ...
... The resulting circuit map represents the connectivity of MS lesion locations that are associated with greater depression severity. To investigate the full topography of this circuit, we intentionally did not apply a statistical threshold, following our previous work 6,8,20 . The topography of our MS circuit (Fig. 3a) showed high spatial correlation with the topography of our convergent a priori depression circuit (spatial r = 0.63) (Fig. 2c), and permutation testing confirmed that this relationship was stronger than chance (P = 0.015; 25,000 permutations). ...
... Once thought to be a sole disorder of the basal ganglia, research has elucidated dystonia to reflect a "circuitopathy", indicating aberrant networks underpinning the pathophysiology. (7,8) Lesion-identification studies have identified spinal cord, basal ganglia, brainstem, cerebellum, and thalamic regions as most affected in patients with cervical dystonia, (9,10) with the brainstem and cerebellum as the most commonly affected regions in a recent study. (11) All lesion sites have been classified to ascertain connectivity with the cerebellum, (10) and surmounting evidence supports cerebellar involvement in dystonic sensorimotor pathophysiology. ...
... Changes in DCC receptor levels in adolescent mice lead to mistargeting of mesolimbic dopamine axons in the NAcc and to their ectopic growth to PFC, altering PFC function and cognitive control in adulthood [17,35]. Similar anatomical and behavioral changes occur in humans that are DCC mutation carriers [36,37], indicating that the Netrin-1/DCC pathway is part of a gene network closely involved in corticolimbic development. ...
... Computational studies have shown that inter-individual variability in neural orientation optimal for stimulation is larger in the prefrontal cortex (PFC) than in the primary motor cortex [43]. Numerous studies have indicated high variability in the optimal PFC target for the treatment of MDD with TMS [44][45][46]. In addition to the coil location, the orientation of the TMS coil with respect to the underlying cortical anatomy impacts the electric field at the target site [21], and a recent modeling study suggests that orientation accounts for as much variability in the simulated TMS response as does location [47]. ...