The world's largest project to unravel the mysteries of the human brain has been thrown into crisis with more than 100 leading researchers threatening to boycott the effort amid accusations of mismanagement and fears that it is doomed to failure.

The European commission launched the €1.2bn (£950m) Human Brain Project (HBP) last year with the ambitious goal of turning the latest knowledge in neuroscience into a supercomputer simulation of the human brain. More than 80 European and international research institutions signed up to the 10-year project.

But it proved controversial from the start. Many researchers refused to join on the grounds that it was far too premature to attempt a simulation of the entire human brain in a computer. Now some claim the project is taking the wrong approach, wastes money and risks a backlash against neuroscience if it fails to deliver.

In an open letter to the European commission on Monday, more than 130 leaders of scientific groups around the world, including researchers at Oxford, Cambridge, Edinburgh and UCL, warn they will boycott the project and urge others to join them unless major changes are made to the initiative.

The researchers urge EC officials who are now reviewing the plans to take a hard look at the science and management before deciding on whether to renew its funding. They believe the review, which is due to conclude at the end of the summer, will find "substantial failures" in the project's governance, flexibility and openness.

Central to the latest controversy are recent changes made by Henry Markram, head of the Human Brain Project at the Swiss Federal Institute for Technology in Lausanne. The changes sidelined cognitive scientists who study high-level brain functions, such as thought and behaviour. Without them, the brain simulation will be built from the bottom up, drawing on more fundamental science, such as studies of individual neurons. The brain, the most complex object known, has some 86bn neurons and 100tn connections.

"The main apparent goal of building the capacity to construct a larger-scale simulation of the human brain is radically premature," Peter Dayan, director of the computational neuroscience unit at UCL, told the Guardian.

"We are left with a project that can't but fail from a scientific perspective. It is a waste of money, it will suck out funds from valuable neuroscience research, and would leave the public, who fund this work, justifiably upset," he said.

Europe's decision to approve the HBP spurred US scientists to propose a major project of their own. The US Brain Initiative aims to map the activity of the human brain and could win $3bn (£1.75bn) in funding over 10 years.

Alexandre Pouget, a signatory of the letter at Geneva University, said that while simulations were valuable, they would not be enough to explain how the brain works. "There is a danger that Europe thinks it is investing in a big neuroscience project here, but it's not. It's an IT project," he said. "They need to widen the scope and take advantage of the expertise we have in neuroscience. It's not too late. We can fix it. It's up to Europe to make the right decision."

But Markram staunchly defends the project, arguing that it was always about developing technology rather than basic neuroscience. He said its goal was not to churn out more of the data that neuroscientists already produce, but to develop new tools to make sense of the vast data sets coming out of brain sciences.

"The rationale of the Human Brain Project is a plan for data: what do we do with all this data? This is a very exciting ICT project that will bring completely new tools and capabilities to all of neuroscience," he said. "It is not a general neuroscience funding source for more of the same research."

Richard Frackowiak, director of clinical neuroscience at the University Hospital of Lausanne, and co-leader of a strand of the Human Brain Project focusing on "future medicine", said that many of the complaints were "irrational sniping" from scientists who were ill-informed, or wanted the funds to pursue their own research agendas. He said that simulations of the brain represented a long-needed "paradigm shift" in neuroscience.

Sir Colin Blakemore, professor of neuroscience at the University of London, who is not one of the signatories to the letter, said: "It's important that the review should be thorough and, if necessary, critical. But it would be unfortunate if this high-profile project were to be abandoned. There's enough flexibility in the plans to allow the project to be refocused and re-energised.

"The most important thing is that the goals should be realistic. If they promise the politicians cures for dementia or miraculous breakthroughs in artificial intelligence, but don't really deliver them, it might have a negative impact on the whole funding of neuroscience in the future – and that would be a disaster.".