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Personalized Brain Maps May Help Improve Deep Brain Stimulation for Parkinson’s, Other Conditions

deep brain stimulation

Not everyone’s brain connections map at exactly the same location, which may explain why deep brain stimulation (DBS) therapy, used for severe cases of Parkinson’s and other neurological conditions, works for some patients and not for others, a study has found.

The findings,”Integrative and Network-Specific Connectivity of the Basal Ganglia and Thalamus Defined in Individuals,” could improve DBS treatment for Parkinson’s patients, by helping doctors choose where in the brain to implant electrodes based on each patient’s own brain maps. The research was published in the journal Neuron.

DBS — a surgical procedure in which electric stimulators are placed at target regions inside the brain — may be used to relieve motor symptoms in some people with Parkinson’s, who have had the disease for at least four years and whose motor symptoms cannot be fully controlled by medication.

It usually works best to ease stiffness, slowness, and tremor, and not as well for imbalance, sudden inability to move when walking, or non-motor symptoms.

For other neurological conditions, DBS can be used to ease cognitive symptoms such as obsessive thoughts and compulsive behaviors.

However, this method is not effective for all patients. In the case of Parkinson’s, it can be transformative for some, but for others, it causes side effects that outweigh the benefits, including worsened thinking or memory problems.

“Deep-brain stimulation is a very invasive treatment that is only done for difficult, severe cases,” one of the study’s leaders, Deanna Greene, PhD, a professor at Washington University School of Medicine in St. Louis, Illinois, (WUSTL) said in a press release.

“So it is difficult to grapple with the fact that such an invasive treatment may only help half the people half the time,” Green said.

She and her colleagues mapped specific circuits in the brain using magnetic resonance imaging (MRI) and found that each person’s brain networks position a bit differently. This may help explain why the effects of DBS vary so much from person to person and point to a potential way of improving the treatment.

It all started when a group of scientists from Washington University scanned themselves at night as part of the so-called Midnight Scan Club.

From the brain scans of 10 healthy individuals, researchers created three-dimensional maps of the functional networks running through structures located deep inside the brain, which usually are targeted by DBS and known as the thalamus and the basal ganglia.

Both these regions have been linked to neurological and psychiatric conditions, but so far the precise mapping of its activity has been  challenging technically.

Researchers discovered that the distinct networks that control vision, movement, attention, goal-directed behaviors, or the brain’s default state at rest, mingle and share information at nine hubs inside the basal ganglia and thalamus.

Importantly, they saw that each person’s functional networks can be positioned a bit differently, so when DBS electrodes are placed in the same anatomical spot they may influence different functions in different people.

Some networks and their connecting spots — such as the motor integration zone, where the control of movement and goal-directed behavior share paths — maintained pretty much the same location in all people. Of note, these regions corresponded to “consistently successful sites of deep brain stimulation,” the researchers wrote.

“I showed a neurosurgeon where we’d found the motor integration zone, and he said, ‘Oh, that’s where we put the electrodes for essential tremor, and it always works,’” said the study’s senior author, Nico Dosenbach, MD, PhD, and a professor at WUSTL.

Conversely, other networks and intersection points — some targeted to treat Parkinson’s disease — varied significantly more from person to person.

“We saw that there was a great deal of variation across people in terms of what functional networks are represented there, and deep-brain stimulation is only about 40% to 50% successful there,” Dosenbach said.

The team is now exploring ways of using each person’s brain map to personalize the best regions to target to provide relief while avoiding side effects. They also want to look for other brain spots that might provide even better results.

“What this study suggests is that a particular patient may do better if the wire is placed in relation to their personal functional brain map rather than in context of the population average. A personalized functional map — as opposed to an anatomical map, which is what we use today — could help us place a wire in the exact place that would provide the patient with the most benefit,” said study co-author Scott Norris, MD, professor at WUSTL.

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Brain MRIs Can Be Used to Detect Early Signs of Parkinson’s Cognitive Impairment, Study Suggests

brain MRI

Brain magnetic resonance imaging (MRI) scans could be used to detect early and subtle markers of cognitive impairment in people with Parkinson’s, which may help predict patients’ prognoses and disease progression, a recent study suggests.

Such early detection also allows people with the neurodegenerative disease to start appropriate care strategies earlier, the researchers say.

The results of the study, “Texture features of magnetic resonance images: A marker of slight cognitive deficits in Parkinson’s disease,” were published in the journal Movement Disorders.

Cognitive impairment is a common non-motor symptom of Parkinson’s disease and a cause of significant disability for patients and a burden for caregivers. The extent and progression of cognitive deficits vary, with about 20.3% to 60.5% of individuals experiencing mild cognitive impairments (MCI). In more severe cases, such impairment can result in dementia.
Those at-risk can benefit from early detection of cognitive alterations, which allows them to initiate appropriate care strategies such as cognitive stimulation therapy. Such therapy can result in a marked improvement in cognition and quality of life, according to researchers. However, standard neuropsychological assessments are time-consuming and not easy to do in routine clinical practice. Moreover, such evaluations can be influenced by medication, pain, anxiety, and other factors.
Therefore, additional markers of cognitive deficits are needed for Parkinson’s patients, the researchers say. One potential option is the use of magnetic resonance imaging (MRI), an imaging exam that uses a powerful magnetic field, radio waves, and a computer to produce detailed pictures of the body’s internal structures.
“Texture features” — a well-known method of MRI image processing used for medical purposes — could offer insights on subtle brain changes.  These features could be used to detect the damage to brain cells, long before any symptoms of cognitive impairment develop.
Recognizing the potential of this method, a team of French researchers now tested whether such signals could be used as early markers of Parkinson’s cognitive impairments — “potentially even before the atrophy [loss of brain volume, a usual sign of cognitive decline] becomes manifest,” they said.

The team investigated if MRI texture analysis is sensitive enough to be an early marker of cognitive alterations, specifically of cognitive slowing, in Parkinson’s patients.

They analyzed brain MRI scans of 102 people with Parkinson’s from centers in Lille, France, and Maastricht, the Netherlands, who were involved in a previous study.

Based on tests of attention, memory, executive function, language, and visuospatial functions, three groups of patients were considered for the study. These groups were cognitively intact patients (PDCN); cognitively intact patients with slight cognitive slowing (PDCN-S); and patients with mild cognitive deficits, particularly in executive functioning (PD-EXE).

A group of 17 age‐matched healthy people (controls) was included for comparison. All participants were examined on a 3T whole-body scanner and T1‐weighted images were acquired.

Six regions of the brain previously reported to suffer from atrophy (volume loss) in Parkinson’s patients with cognitive impairments were specifically chosen by the researchers for analysis. These regions were the thalamus, the hippocampus, the puramen, the pallidum, the caudate nucleus, and the amygdala.

The researchers found that values for two texture features — skewness and entropy — could distinguish individuals who had normal cognition from those with slight cognitive slowing, and from those with mild impairments. Skewness is a parameter that quantifies the asymmetry of the intensity of MRI signals. Entropy represents the degree of uncertainty of the texture intensity.

These texture features were at three specific regions in the brain: the hippocampus, the thalamus, and the amygdala.

The values for these features gradually decreased in those patients with worse cognitive function, suggesting it is possible to detect early cognition deficits in people with Parkinson’s using MRIs. The researchers noted that the best performances regarding sensitivity and specificity were obtained by measuring skewness in the hippocampus. In fact, skewness in the hippocampus was a significant marker of slight cognitive slowing.
“Our results suggest that hippocampal neurons could be affected very early in PD patients, even before atrophy can be detected with commonly used methods, and this could cause a general slowing of information processing,” the researchers said.
“These results support the assumption that signal alterations associated with Parkinson’s disease–related cognitive decline can be captured very early by texture analysis,” they added.
The researchers believe that brain MRI imaging could be combined with other methods, such as cognitive assessments and electroencephalograms. That would allow scientists to build a combined model “not only for the profiling but also for the prognosis and the prediction of evolution” of cognitive impairment, they said.

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